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DOI: 10.1039/C3OB41644E
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Pd(II)-catalyzed direct C–H acylation of N-Boc hydrazones with aldehydes: one-pot synthesis of 1,2-diacylbenzenes Satyasheel Sharma,a Aejin Kim,a Jihye Park,a Mirim Kim,a Jong Hwan Kwak,a Young Hoon Jung,a Jung Su Park,b,* and In Su Kima,* 5
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Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX DOI: 10.1039/b000000x A palladium(II)-catalyzed direct acylation of acetophenone N-Boc hydrazones with aldehydes via C–H bond activation is described. This protocol provides direct access to a range of 1,2-diacylbenezenes, which are useful precursors to construct biologically interesting and pharmaceutically important compounds.
Introduction
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Aryl ketones are important structural scaffolds found in natural products, medicinally relevant molecules, and functional materials.1 Notably, 1,2-diacylbenzenes are known to be crucial synthetic precursors due to the high prevalence of biologically active compounds and pharmaceuticals such as phthalazines, Narylphthalimidines, isobenzofurans, indanones, isoindoles, isoindolines, and isoquinolines.2 Also, 1,2-diacylbenzenes are receiving increasing attention as fluorescence reagents for both qualitative and quantitative high-sensitivity analysis for amino acids and peptides.3 In particular, 1,2-diacylbenzenes were used in a fluorometric assay for biotinase due to their ability to react selectively with lysine.4 These facts have led to develop an efficient method for the preparation of 1,2-diacylbenzenes. General methods for the construction of 1,2-diacylbenzenes include oxidation of N-aroylhydrazones of o-hydroxyaryl ketone acylhydrazones with lead tetraacetate5 or hypervalent iodine reagents.6 However, from a synthetic point of view, all these reactions present intrinsic drawbacks, which include the use of toxic reagents, poor functional group tolerance, harsh reaction conditions, and the requirement of prefunctionalized starting materials. Therefore, it is highly desirable to develop atomeconomical protocols that involve fewer synthetic steps and readily available starting materials for the preparation of 1,2diacylbenzenes. Transition metal-catalyzed dehydrogenative cross-coupling reactions via selective C–H bond activation have emerged as a powerful tool to produce structurally diverse organic molecules, because such methods avoid a preparation of preactivated starting materials and a production of stoichiometric metallic waste.7 Thus, cross-coupling reactions via C–H bond activation can lead to an improved overall efficiency of the desired transformation. Recently, transition metal-catalyzed oxidative acylations of inactive sp2 C–H bonds with aldehydes and alcohols as acyl sources have been described.8 Catalytic decarboxylative acylations of aromatic C–H bonds using α-oxocarboxylic acids as This journal is © The Royal Society of Chemistry [year]
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acyl surrogates were also reported.9 In addition, a palladiumcatalyzed acylation of 2-arylpyridines and acetanilides via oxidation of benzylic C–H bonds in toluene derivatives was demonstrated.10 Notably, Yu8e and Li8f respectively disclosed efficient ways to prepare ortho-acylated acetophenone O-methyl oximes as the precursors for 1,2-diacylbenzenes via palladiumand rhodium-catalyzed oxidative coupling reactions between acetophenone O-methyl oximes and aldehydes. However, these approaches are required an additional step to remove the oxime directing group for the preparation of 1,2-diacylbenzenes. Ph cat. Pd(OAc)2 Cu(OAc)2, AgO2CCF3 Ph NNHTs
N N Ts ref. 12a Ph
cat. [RhCp*Cl2]2 Cu(OAc)2•H2O
H
H
N N
Ts
CO2R CO2R ref. 12b
Me N
R cat.CuSO4, CuI
N H
H
N
N R
Pyridine, TFA, O2, DMF ref. 12c Me
Me NNHBoc
cat. Pd(OAc)2, TBHP O
H H
R
O O R this work
Figure 1 Hydrazone directing groups in C–H bond activation.
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65
Hydrazones are common protection groups of the ketone moiety, and have become versatile cross-coupling partners in transition metal-catalyzed reactions.11 However, hydrazones have been rarely used as directing groups of C–H bond activation protocols.12 For examples, Inamoto and Hiroya described a Pdcatalyzed C–H activation of N-tosylhydrazones followed by intramolecular amination to afford highly substituted indazoles (Figure 1).12a Xu and coworkers reported a Rh-catalyzed tandem C–H olefination and annulations between sulfonylhydrazones and
[journal], [year], [vol], 00–00 | 1
Organic & Biomolecular Chemistry Accepted Manuscript
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DOI: 10.1039/C3OB41644E
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Table 1 Selected optimization of reaction conditionsa
Results and discussion Our initial investigation focused on the coupling of p-CF3acetophenone N-substituted hydrazones with benzaldehyde to afford 1,4-disubstituted phthalazines with interesting luminescent13 and anticancer activities14 by tandem acylation and intramolecular cyclization (Scheme 1, eq. 1). After extensive screening of hydrazones with =NNH-Boc, =NNH-H, =NNH-Moc and =NNH-Ts directing groups, all reactions provide a mixture of p-CF3-acetophenone, acylated hydrazones and 1,2diacylbenzenes, instead of the phthalazine compounds (Scheme 1, eqs. 2 and 3). Interestingly, p-CF3-acetophenone N-Boc hydrazone (1a) was found to couple with 2 equiv. of benzaldehyde (2a) in the presence of 10 mol % of Pd(OAc)2 and 3 equiv. of TBHP in DCE solvent at 70 oC for 10 h to afford 1,2diacylbenzene 3a in 58% yield (Table 1, entry 1). Thus, hydrazone derivative 1a was chosen as an optimal substrate for the preparation of 1,2-diacylbenzene product. Me N F3C
H N
O R
+
H
Ph
H
acylation & annulation (eq. 1)
acylation & hydrolysis (eq. 3)
acylation
60
(eq. 2) Me
Me Me
N N
F3C Ph
F3C
N O
H N
R F3C
O O Ph
Ph
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Scheme 1 Catalytic acylation strategy of hydrazone directing groups.
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45
Screening of oxidants showed that TBHP is superior to other oxidants such as (PhCOO)2, Ag2O and (NH4)2S2O8 (Table 1, entries 2–4). Further screening of the effect of palladium revealed that Pd(OAc)2 was found to be most effective in this coupling reaction (Table 1, entries 5 and 6). After screening of solvents under otherwise identical conditions, DCE was found to be the most effective solvent in this coupling reaction, whereas other solvents such as toluene, THF, MeCN and DMF failed to facilitate high levels of conversion (Table 1, entries 7–10). Further study showed that AcOH additive displayed the decreased catalytic activity (Table 1, entry 11). Logically, it was thought that the formation of 3a can be controlled by the amount of catalyst, oxidant and aldehyde (Table 1, entries 12–14). Indeed, 2 | Journal Name, [year], [vol], 00–00
Entry
Pd catalyst (mol %)
Oxidant (equiv.)
Solvent
Yield (%)b
1
Pd(OAc)2 (10)
TBHP (3)
DCE
58
2
Pd(OAc)2 (10)
(PhCOO)2 (3)
DCE
24
3
Pd(OAc)2 (10)
Ag2O (3)
DCE
N.R.
4
Pd(OAc)2 (10)
(NH4)2S2O8 (3)
DCE
N.R.
5
Pd(TFA)2 (10)
TBHP (3)
DCE
28
6
PdCl2 (10)
TBHP (3)
DCE
22
7
Pd(OAc)2 (10)
TBHP (3)
toluene
46
8
Pd(OAc)2 (10)
TBHP (3)
THF
24
9
Pd(OAc)2 (10)
TBHP (3)
MeCN
51
10
Pd(OAc)2 (10)
TBHP (3)
DMF
N.R.
11c
Pd(OAc)2 (10)
TBHP (3)
DCE
50
12
Pd(OAc)2 (10)
TBHP (4)
DCE
63
13
Pd(OAc)2 (5)
TBHP (4)
DCE
48
14d
Pd(OAc)2 (10)
TBHP (4)
DCE
71
15d,e
Pd(OAc)2 (10)
TBHP (4)
DCE
N.R.
a 55
35
the use of 3 equiv. of benzaldehyde (2a) and 4 equiv. of TBHP afforded our desired product 3a in high yield (71%), as shown in entry 14. In addition, this coupling reaction did not proceed at room temperature, even for longer reaction time (Table 1, entry 15).
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Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), Pd catalyst (quantity noted), oxidant (quantity noted), solvent (1 mL) at 70 oC for 10 h in pressure tubes. b Isolated yield by flash column chromatography. c AcOH (50 mol %) was added as an additive. d 2a (0.9 mmol, 3 equiv.). e Room temperature, 20 h.
With the optimized reaction conditions in hand, the scope and limitation of the aldehyde were examined, as shown in Table 2. The coupling of p-CF3-acetophenone N-Boc hydrazone (1a) and aldehydes 2b–2g with electron-donating (OMe, OBn and Me) and electron-withdrawing groups (CF3, F and Cl) at the paraposition on the aromatic ring was found to be favored in the acylation reaction to afford the corresponding products 3b–3g in moderate to high yields. In addition, meta-substituted benzaldehydes 2h–2j smoothly underwent this coupling reaction to generate the corresponding products. Notably, omethoxybenzaldehyde 2k and o-fluoro-p-methoxybenzaldehyde 2l proved to be good substrates for this transformation, affording the corresponding products 3k and 3l. However, heterocyclic benzaldehydes and aliphatic aldehydes failed to deliver the coupling products with the current catalytic system. To further explore the substrate scope and limitations of this process, a broad range of acetophenone or benzophenone N-Boc hydrazones 1b–1m was screened to couple with benzaldehyde (2a), as shown in Table 3.
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Organic & Biomolecular Chemistry Accepted Manuscript
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alkenes to give 1,2-dihydrophthalazines.12b Recently, Ge et al. disclosed a Cu-catalyzed dehydrogenative intramolecular cyclization of N-methyl-N-phenylhydrazones to provide cinnolines.12c As part of an ongoing research program directed toward the development of catalytic acylation reactions of inactive C–H bonds, we became interested in developing an efficient synthetic route to 1,2-diacylbenzenes via C–H bond activation. Herein we present the tandem palladium-catalyzed ortho-acylation and deprotection of acetophenone N-Boc hydrazones with aldehydes under tert-butyl hydroperoxide (TBHP) as a convenient oxidant to afford 1,2-diacylbenzenes. To the best of our knowledge, it is the first report of direct catalytic acylation for the formation of 1,2-diacylbenzenes.
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Table 2 Scope of aldehydesa Me
Me
F3C
+
R
H
H 1a
o
DCE, 70 C, 10 h
Me
O O
R 3a-3l (%)b
F3C
Me
O O
F3C
O O
F3C
2a-2l
Me
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Pd(OAc)2 (10 mol %) TBHP (4 equiv.)
O
NNHBoc
O O
F3C
20
Me O O
F3C
25
OMe 3b (69%)
3a (71%) Me O O
F3C
OBn 3c (61%)
Me
CF3
O O
F3C
F
3e (55%)
Me
Me
O O
F3C
Me 3d (50%)
Cl 3g (63%)
3f (72%)
O O
F3C
30
3h (60%) 35
Me
Me
O O
F3C
Me
O O
F3C
Me
F3C
O O
O O
F3C
F
OMe OMe 3i (55%)
Cl 3j (48%)
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Cl 3k (55%)
OMe 3l (67%)
a 5
Reaction conditions: 1a (0.3 mmol), 2a–2l (0.9 mmol), Pd(OAc)2 (10 mol %), TBHP (1.2 mmol), DCE (1 mL) at 70 oC for 10 h in pressure tubes. b Isolated yield by flash column chromatography.
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Table 3 Scope of acetophenone N-Boc hydrazonesa 50
found to be favored in the acylation reaction to afford the corresponding products 4b–4g in good yields. Notably, the bromo and chloro moieties on the aromatic ring were tolerated under these coupling conditions and offers versatile synthetic functionality for further elaboration. The reaction of metasubstituted acetophenone N-Boc hydrazones 1h and 1i preferentially occurred at the less hindered position to afford the corresponding product 4h and 4i in good yields as a single regioisomer. However, fluoro-substituted acetophenone N-Boc hydrazone 1j at the meta-position furnished the acylated products 4ja and 4jb in 50% yield, providing the regioisomers at C6 and C2 with 2:1 ratio. These data suggest that the steric effect of the substrates strongly interferes with either the formation of the cyclopalladated intermediate or the proximity of the acyl radical into the cyclopalladated intermediate. The ortho-substituted acetophenone N-Boc hydrazones 1k–1m were also found to be favored in this catalyst system. In addition, benzophenone N-Boc hydrazone (1n) was smoothly converted to the corresponding product 4n in 40% yield. Some control experiments were performed to obtain a mechanistic insight. Treatment of 4-fluoroacetophenone (5a) and benzaldehyde (2a) under standard reaction conditions provided no formation of our desired product 4f (Scheme 2, eq. 1). This result indicates that the hydrazone directing group can initiate ortho-selective cyclopalladation on the arene ring by Pd(OAc)2 prior to the cleavage of hydrazone group. 4-Fluoroacetophenone N-Boc hydrazones (1f) was hydrolyzed to the corresponding acetophenone 5a in the presence of TBHP irrespective of whether Pd(OAc)2 was present or not, thus suggesting that hydrazone directing group might be cleaved by TBHP (Scheme 2, eqs. 2 and 3). However, in the presence of aldehyde 2a under standard reacton conditions for 2 h, the reaction furnished the drastically increased formation of our desired product 4f and the reaction intermediate hydrazone 6a (Scheme 2, eq. 4). This observation suggests that the rate of acylation process is significantly faster than those of the hydrolysis of hydrazone group. Me
Me O
+
H
H
F
standard conditions
O
5a
Ph
O O
F
10 h
(eq. 1)
Ph 4f (not observed)
2a Me NNHBoc
F
TBHP (4 equiv.)
1f
H
+ 5a
(eq. 2)
ratio = 60:40 by crude NMR analysis
DCE, 70 oC 2h
1f standard conditions
1f
1f
1f
1f
10
15
Reaction conditions: 1b–1n (0.3 mmol), 2a (0.9 mmol), Pd(OAc)2 (10 mol %), TBHP (1.2 mmol), DCE (1 mL) at 70 oC for 10 h in pressure tubes. b Isolated yield by flash column chromatography.
This journal is © The Royal Society of Chemistry [year]
+ 5a
+
4f
NNHBoc O
+ F
(eq. 4)
Ph ratio = 27:18:44:11 by crude NMR analysis
a
The coupling of benzaldehyde (2a) and acetophenone N-Boc hydrazones 1b–1g with electron-rich and electron-deficient groups (OMe, Br, Cl, F and NO2,) at the para-positions was
2h
(eq. 3)
Me
standard conditions
+ 2a
+ 5a
ratio = 35:75 by crude NMR analysis
2h
6a
Scheme 2 Control experiments. 55
On the basis of these collective data, a plausible mechanism is proposed as illustrated in Scheme 3. First, a coordination of the N atom of 1b to Pd(II) and the subsequent directed cyclopalladation Journal Name, [year], [vol], 00–00 | 3
Organic & Biomolecular Chemistry Accepted Manuscript
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General procedure for the synthesis of acetophenone N-Boc hydrazones: Acetophenone N-Boc hydrazones were synthesized according to the procedure reported in the literature.18 45
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10
Scheme 3 Plausible reaction mechanism.
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Typical procedure for the acylation of N-Boc hydrazones (3a– l and 4b–m): To an oven-dried sealed tube with p-CF3acetophenone N-Boc hydrazone (1a) (90.6 mg, 0.3 mmol, 100 mol %), Pd(OAc)2 (6.7 mg, 0.03 mmol, 10 mol %), benzaldehyde (2a) (95.4 mg, 0.9 mmol, 300 mol %) in anhydrous DCE (1 mL) was added TBHP (0.22 mL, 1.2 mmol, 400 mol %, 5.5 M in decane). The reaction mixture was allowed to stir at 70 ºC for 10 h. After cooling at room temperature, the reaction mixture was evaporated onto silica gel. Purification of the product by flash column chromatography (SiO2: n-hexanes/EtOAc) provided the corresponding product 3a (62.2 mg) in 71% yield. 1-(2-Benzoyl-4-(trifluoromethyl)phenyl)ethanone (3a): 1H NMR (700 MHz, CDCl3) δ 7.97 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.67 (s, 1H), 7.58 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 8.0 Hz, 2H), 2.55 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.9, 196.0, 141.3, 140.8, 136.4, 133.6 (q, JC-F = 33.4 Hz), 133.5, 129.5, 129.4, 128.7, 126.8 (q, JC-F = 3.8 Hz), 125.3 (q, JC-F = 3.1 Hz), 123.1 (q, JC-F = 272.8 Hz), 27.8; IR (KBr) υ 2854, 1738, 1694, 1674, 1451, 1366, 1315, 1262, 1177, 1132, 1089, 750 cm-1; HRMS (EI) m/z calcd for C16H11F3O2 [M]+ 292.0711; found 292.0709.
Conclusions
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In conclusion, a hydrazone-directed Pd-catalyzed ortho-acylation of acetophenone N-Boc hydrazones with aldehydes has been developed, which is an effective approach to direct access of various 1,2-diacylbenzenes. These transformations have been applied to a wide range of substrates, and typically proceed with excellent level of chemoselectivity as well as with high functional group tolerance. Further applications of this method to the synthesis of biologically active compounds are in progress.
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Experimental General Methods: Commercially available reagents were used without additional purification, unless otherwise stated. Sealed tubes (13 × 100 mm2) were purchased from Fischer Scientific and dried in oven for overnight and cooled under a stream of nitrogen prior to use. Thin layer chromatography was carried out using plates coated with Kieselgel 60F254 (Merck). For flash column chromatography, E. Merck Kieselgel 60 (230-400 mesh) was used. Nuclear magnetic resonance spectra (1H and 13C NMR) were recorded on a Bruker Unity 400 MHz and 700 MHz spectrometer for CDCl3 solutions and chemical shifts are reported as parts per million (ppm) relative to, respectively, residual CHCl3 δH (7.24 ppm) and CDCl3 δC (77.2 ppm) as internal standards. Resonance patterns are reported with the notations s (singlet), d (doublet), t (triplet), q (quartet), and m (multiplet). In addition, the notation br is used to indicate a broad signal. Coupling constants (J) are reported in hertz (Hz). IR spectra were recorded on a Varian 2000 Infrared spectrophotometer and are reported as cm-1. High-resolution mass spectra (HRMS) were recorded on a JEOL JMS-600 spectrometer. 4 | Journal Name, [year], [vol], 00–00
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1-(2-(4-Methoxybenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3b): 1H NMR (700 MHz, CDCl3) δ 7.93 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.65 (s, 1H), 6.93 (d, J = 8.9 Hz, 2H), 3.86 (s, 3H), 2.54 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.2, 194.7, 163.9, 141.5, 140.9, 133.4 (q, JC-F = 33.2 Hz), 131.9, 129.4, 129.3, 126.5 (q, JC-F = 3.7 Hz), 125.3 (q, JC-F = 3.6 Hz), 123.2 (q, JC-F = 272.4 Hz), 114.0, 55.5, 28.1; IR (KBr) υ 2833, 1717, 1680, 1640, 1525, 1451, 1289, 1223, 1148, 1105, 1031, 805, 746 cm-1; HRMS (EI) m/z calcd for C17H13F3O3 [M]+ 322.0817; found 322.0825. 1-(2-(4-(Benzyloxy)benzoyl)-4(trifluoromethyl)phenyl)ethanone (3c): 1H NMR (700 MHz, CDCl3) δ 7.94 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.65 (s, 1H), 7.43–7.34 (m, 4H), 7.35–7.34 (m, 1H), 7.02 (d, J = 8.9 Hz, 2H), 5.13 (s, 2H), 2.54 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.4, 194.7, 163.1, 141.5, 140.9, 136.0, 133.4 (q, JC-F = 33.0 Hz), 131.9, 129.6, 129.3, 128.7, 128.3, 127.5, 126.6 (q, JC-F = 3.8 Hz), 125.3 (q, JC-F = 3.2 Hz), 123.2 (q, JC-F = 273.0 Hz), 114.8, 70.2, 28.1; IR (KBr) υ 1739, 1665, 1599, 1573, 1455, 1423, 1367, 1338, 1257, 1172, 1133, 1089, 765 cm-1; HRMS (EI) m/z calcd for C23H17F3O3 [M]+ 398.1130; found 398.1130. 1-(2-(4-Methylbenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3d): 1H NMR (700 MHz, CDCl3) δ 7.95 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.65 (s, 1H), 7.63 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.5 Hz, 2H), 2.54 (s, 3H), 2.41 (s, 3H), 3.60 (s, 3H); 13 C NMR (175 MHz, CDCl3) δ 198.1, 195.8, 144.6, 141.5, 140.9, 133.9, 133.5 (q, JC-F = 31.9 Hz), 129.6, 129.4, 129.3, 126.7 (q, JCThis journal is © The Royal Society of Chemistry [year]
Organic & Biomolecular Chemistry Accepted Manuscript
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provides a 5-membered palladacycle I.15 At the same time, the tBuO· radical generated from TBHP can abstract H atom from the aldehyde to give a reactive acyl radical.16 The palladacycle I can react with a benzoyl radical to afford the dimeric Pd(III) or Pd(IV) intermediate II,17 which can undergo reductive elimination to afford the acylated hydrazone III and regenerate Pd(II) catalyst. Finally, the acylated hydrazone III is rapidly converted to our desired 1,2-diacylbenzene 4b by TBHP.
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1-(4-(Trifluoromethyl)-2-(4(trifluoromethyl)benzoyl)phenyl)ethanone (3e): 1H NMR (700 MHz, CDCl3) δ 8.04 (d, J = 8.1 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 8.1 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H), 7.65 (s, 1H), 2.58 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.4, 195.0, 141.0, 140.1, 139.2, 134.4 (q, JC-F = 21.8 Hz), 134.3 (q, JC-F = 17.5 Hz), 129.9, 127.2 (q, JC-F = 3.1 Hz), 127.0, 125.8 (q, JC-F = 3.9 Hz), 125.1 (q, JC-F = 3.0 Hz), 123.0 (q, JC-F = 271.7 Hz), 122.7 (q, JC-F = 271.5 Hz), 27.4; IR (KBr) υ 2947, 2833, 1721, 1680, 1639, 1525, 1451, 1325, 1290, 1217, 1148, 1107, 1032, 741 cm-1; HRMS (EI) m/z calcd for C17H10F6O2 [M]+ 360.0585; found 360.0580. 1-(2-(4-Fluorobenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3f): 1H NMR (700 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.76–7.74 (m, 2H), 7.64 (s, 1H), 7.13–7.11 (m, 2H), 2.57 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.7, 194.6, 165.8 (d, JC-F = 254.6 Hz), 141.2, 140.4, 133.8 (q, JC-F = 33.8 Hz), 132.9, 132.0 (d, JC-F = 9.2 Hz), 129.7, 126.9 (q, JC-F = 4.2 Hz), 125.1 (q, JC-F = 3.6 Hz), 123.1 (q, JC-F = 271.3 Hz), 115.9 (d, JC-F = 22.6 Hz), 27.7; IR (KBr) υ 1693, 1674, 1599, 1505, 1409, 1362, 1300, 1261, 1178, 1134, 1089, 1014, 967, 906, 851, 766 cm-1; HRMS (EI) m/z calcd for C16H10F4O2 [M]+ 310.0617; found 310.0605.
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NMR (175 MHz, CDCl3) δ 197.8, 195.9, 159.9, 141.4, 140.7, 137.8, 133.7 (q, JC-F = 33.1 Hz), 129.7, 129.6, 129.4, 126.8 (q, JCF = 2.9 Hz), 125.4 (q, JC-F = 2.9 Hz), 123.9 (q, JC-F = 271.5 Hz), 122.4, 120.2, 55.5, 27.8; IR (KBr) υ 1739, 1694, 1597, 1582, 1487, 1432, 1366, 1336, 1270, 1218, 1176, 1131, 1089, 1045, 970, 908, 840, 792 cm-1; HRMS (EI) m/z calcd for C17H13F3O3 [M]+ 322.0817; found 322.0817. 1-(2-(3,5-Dichlorobenzoyl)-41 (trifluoromethyl)phenyl)ethanone (3j): H NMR (700 MHz, CDCl3) δ 8.06 (d, J = 8.1 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.62 (s, 1H), 7.54–7.53 (m, 3H), 2.60 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.2, 193.6, 140.5, 139.7, 139.1, 135.7, 134.5 (q, JC-F = 33.2 Hz), 133.0, 130.1, 127.3 (q, JC-F = 3.1 Hz), 127.2, 125.0 (q, JC-F = 3.8 Hz), 123.7 (q, JC-F = 271.5 Hz), 27.3; IR (KBr) υ 2946, 2833, 1717, 1681, 1638, 1567, 1415, 1326, 1291, 1233, 1163, 1144, 1026, 875, 802, 758 cm-1; HRMS (EI) m/z calcd for C16H9Cl2F3O2 [M]+ 359.9932; found 359.9931. 1-(2-(2-Methoxybenzoyl)-4-(trifluoromethyl)phenyl)ethanone 1 (3k): H NMR (700 MHz, CDCl3) δ 7.78–7.74 (m, 3H), 7.60 (s, 1H), 7.55–7.52 (m, 1H), 7.08 (t, J = 8.4 Hz, 1H), 6.95 (d, J = 8.3 Hz, 1H), 3.59 (s, 3H), 2.51 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 200.0, 194.8, 158.8, 142.3, 142.2, 134.6, 132.6 (q, JC-F = 33.0 Hz), 131.5, 128.2, 126.8 (q, JC-F = 3.7 Hz), 126.1, 125.4 (q, JC-F = 3.4 Hz), 124.1 (q, JC-F = 271.3 Hz), 121.0, 112.1, 55.5, 28.7; IR (KBr) υ 2946, 2833, 1716, 1680, 1642, 1525, 1450, 1399, 1324, 1292, 1237, 1161, 1106, 1020, 804, 759 cm-1; HRMS (EI) m/z calcd for C17H13F3O3 [M]+ 322.0817; found 322.0817.
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1-(2-(4-Chlorobenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3g): 1H NMR (700 MHz, CDCl3) δ 8.00 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.65 (d, J = 8.6 Hz, 2H), 7.64 (s, 1H), 7.42 (d, J = 8.6 Hz, 2H), 2.57 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.6, 194.9, 141.1, 140.3, 140.0, 134.9, 133.9 (q, JC-F = 33.1 Hz), 130.6, 129.7, 129.1, 127.0 (q, JC-F = 3.0 Hz), 125.1 (q, JC-F = 3.9 Hz), 123.1 (q, JC-F = 271.1 Hz), 27.6; IR (KBr) υ 1730, 1693, 1588, 1488, 1366, 1335, 1260, 1175, 1133, 1090, 966, 905, 845, 751 cm-1; HRMS (EI) m/z calcd for C16H10ClF3O2 [M]+ 326.0321; found 326.0329. 1-(2-(2-Naphthoyl)-4-(trifluoromethyl)phenyl)ethanone (3h): 1 H NMR (700 MHz, CDCl3) δ 8.05 (s, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.97–7.95 (m, 1H), 7.94–7.92 (m, 1H), 7.89 (t, J = 8.1 Hz, 2H), 7.84 (d, J = 8.1 Hz, 1H), 7.74 (s, 1H), 7.60 (t, J = 8.1 Hz, 1H), 7.52 (t, J = 8.1 Hz, 1H), 2.55 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.9, 196.1, 141.5, 140.9, 135.8, 134.6, 133.9, 133.7 (q, JC-F = 33.1 Hz), 132.4, 131.6, 129.6, 129.5, 128.8, 127.9, 126.9, 126.8 (q, JC-F = 3.3 Hz), 125.5 (q, JC-F = 3.8 Hz), 124.5, 123.9 (q, JC-F = 271.5 Hz), 27.9; IR (KBr) υ 2923, 2852, 1737, 1693, 1626, 1576, 1491, 1433, 1359, 1335, 1262, 1199, 1132, 1088, 1019, 964, 905, 866, 801, 777 cm-1; HRMS (EI) m/z calcd for C20H13F3O2 [M]+ 342.0868; found 342.0867. 1-(2-(3-Methoxybenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3i): 1H NMR (700 MHz, CDCl3) δ 7.97 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.41–7.40 (m, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.13–7.11 (m, 2H), 3.85 (s, 3H), 2.55 (s, 3H); 13C
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1-(2-(2-Fluoro-4-methoxybenzoyl)-4(trifluoromethyl)phenyl)ethanone (3l): 1H NMR (700 MHz, CDCl3) δ 7.92 (t, J = 8.6 Hz, 2H), 7.80 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 6.81 (dd, J = 8.8, 2.4 Hz, 1H), 6.53 (dd, J = 12.7, 2.3 Hz, 1H), 3.85 (s, 3H), 2.57 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.2, 191.5, 165.4 (d, JC-F = 11.3 Hz), 164.0 (d, JC-F = 255.1 Hz), 144.4, 139.8, 133.6 (q, JC-F = 33.0 Hz), 132.6 (d, JC-F = 2.5 Hz), 129.3, 126.5 (d, JC-F = 3.2 Hz), 124.4, 124.0 (q, JC-F = 271.4 Hz), 117.8 (d, JC-F = 10.1 Hz), 111.0, 101.8 (d, JC-F = 26.0 Hz), 56.0, 27.7; IR (KBr) υ 1777, 1681, 1615, 1527, 1439, 1394, 1325, 1288, 1229, 1161, 1100, 1063, 999, 941, 816, 760 cm-1; HRMS (EI) m/z calcd for C17H12F4O3 [M]+ 340.0723; found 340.0726. 1-(2-Benzoylphenyl)ethanone (4b): 1H NMR (700 MHz, CDCl3) δ 7.88 (d, J = 7.6 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.53 (t, J = 7.3 Hz, 1H), 7.42–7.40 (m, 3H), 2.51 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.5, 197.8, 140.9, 137.5, 137.2, 133.0, 132.2, 129.7, 129.3, 129.2, 128.5, 128.3, 27.4; IR (KBr) υ 1682, 1596, 1571, 1481, 1449, 1359, 1314, 1267, 1153, 1073, 960, 930, 762 cm-1; HRMS (EI) m/z calcd for C15H12O2 [M]+ 224.0837; found 224.0837. 1-(2-Benzoyl-4-methoxyphenyl)ethanone (4c): 1H NMR (700 MHz, CDCl3) δ 7.73 (d, J = 8.3 Hz, 2H), 7.51 (t, J = 7.3 Hz, 2H), 7.40 (t, J = 8.1 Hz, 2H), 7.03 (dd, J = 8.7, 2.5 Hz, 1H), 6.85 (s, 1H), 3.87 (s, 3H), 2.46 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.5, 196.1, 163.0, 143.9, 137.0, 132.9, 131.9, 129.3, 129.1,
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= 4.1 Hz), 125.3 (q, JC-F = 4.0 Hz), 123.2 (q, JC-F = 270.9 Hz), 28.0, 21.8; IR (KBr) υ 2946, 2832, 1716, 1679, 1637, 1526, 1451, 1408, 1327, 1295, 1235, 1143, 1104, 1036, 790 cm-1; HRMS (EI) m/z calcd for C17H13F3O2 [M]+ 306.0868; found 306.0869. F
Organic & Biomolecular Chemistry
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DOI: 10.1039/C3OB41644E
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1-(2-Benzoyl-4-bromophenyl)ethanone (4d): 1H NMR (700 MHz, CDCl3) δ 7.76–7.71 (m, 4H), 7.55 (t, J = 7.4 Hz, 1H), 7.52 (s, 1H), 7.43 (t, J = 8.1 Hz, 2H), 2.49 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.2, 196.0, 142.8, 136.6, 136.0, 133.3, 132.7, 131.2, 130.7, 129.3, 128.6, 127.5, 27.3; IR (KBr) υ 1684, 1582, 1554, 1449, 1424, 1360, 1314, 1287, 1266, 1179, 1158, 1094, 1025, 962, 886, 825, 766 cm-1; HRMS (EI) m/z calcd for C15H11BrO2 [M]+ 301.9942; found 301.9938. 1-(2-Benzoyl-4-chlorophenyl)ethanone (4e): 1H NMR (700 MHz, CDCl3) δ 7.82 (d, J = 8.3 Hz, 1H), 7.72 (d, J = 8.3 Hz, 2H), 7.56–7.54 (m, 2H), 7.43 (t, J = 8.2 Hz, 2H), 7.37 (s, 1H), 2.50 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.0, 196.1, 142.7, 139.0, 136.6, 135.5, 133.3, 130.7, 129.7, 129.2, 128.6, 128.4, 27.3; IR (KBr) υ 1684, 1588, 1557, 1449, 1424, 1360, 1314, 1266, 1159, 1074, 964, 887, 809, 746 cm-1; HRMS (EI) m/z calcd for C15H11ClO2 [M]+ 258.0448; found 258.0455. 1-(2-Benzoyl-4-fluorophenyl)ethanone (4f): 1H NMR (700 MHz, CDCl3) δ 7.93 (dd, J = 8.6, 5.1 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.55 (t, J = 8.1 Hz, 1H), 7.42 (t, J = 8.1 Hz, 2H), 7.26 (m, 1H), 7.09 (dd, J = 8.1, 2.5 Hz, 1H), 2.50 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 196.5, 196.1, 165.5 (d, JC-F = 256.1 Hz), 144.2 (d, JC-F = 7.1 Hz), 136.5, 133.3 (d, JC-F = 2.9 Hz), 133.2, 132.0 (d, JCF = 8.7 Hz), 129.2, 128.6, 116.3 (d, JC-F = 21.6 Hz), 115.7 (d, JC-F = 23.1 Hz), 27.1; IR (KBr) υ 2852, 1738, 1681, 1599, 1580, 1451, 1409, 1363, 1264, 1212, 854, 749 cm-1; HRMS (EI) m/z calcd for C15H11FO2 [M]+ 242.0743; found 242.0741. 1-(2-Benzoyl-4-nitrophenyl)ethanone (4g): 1H NMR (700 MHz, CDCl3) δ 8.41 (dd, J = 8.4, 2.3 Hz, 1H), 8.24 (d, J = 2.2 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 8.2 Hz, 2H), 2.56 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.7, 194.8, 149.0, 143.1, 141.9, 135.9, 133.8, 129.8, 129.5, 128.8, 124.8, 123.4, 28.1; IR (KBr) υ 2853, 1682, 1599, 1450, 1410, 1360, 1314, 1265, 1160, 1074, 964, 886 cm-1; HRMS (EI) m/z calcd for C15H11NO4 [M]+ 269.0688; found 269.0690. 1-(2-Benzoyl-5-methylphenyl)ethanone (4h): 1H NMR (700 MHz, CDCl3) δ 7.74 (d, J = 8.3 Hz, 2H), 7.63 (s, 1H), 7.52 (t, J = 8.1 Hz, 1H), 7.42–7.39 (m, 3H), 7.31 (d, J = 7.7 Hz, 1H), 2.49 (s, 6H); 13C NMR (175 MHz, CDCl3) δ 199.2, 197.8, 140.2, 138.4, 137.8, 137.4, 132.8, 132.5, 129.7, 129.3, 128.6, 128.4, 127.7, 21.4; IR (KBr) υ 2922, 1735, 1681, 1600, 1451, 1359, 1277, 1200, 1055, 1015, 934, 832, 708 cm-1; HRMS (EI) m/z calcd for C16H14O2 [M]+ 238.0994; found 238.1006. 1-(3-Benzoylnaphthalen-2-yl)ethanone (4i): 1H NMR (700 MHz, CDCl3) δ 8.39 (s, 1H), 8.01 (d, J = 7.7 Hz, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.86 (s, 1H), 7.80 (d, J = 8.3 Hz, 2H), 7.68–7.64 (m, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.42 (d, J = 8.2 Hz, 2H), 2.63 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.2, 196.4, 136.6, 136.1, 6 | Journal Name, [year], [vol], 00–00
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134.6, 133.0, 131.8, 131.6, 129.9, 128.4, 128.3, 128.1, 127.9, 127.6, 127.4, 127.1, 26.2; IR (KBr) υ 2923, 1738, 1677, 1597, 1459, 1359, 1313, 1277, 1219, 1198, 1123, 1023, 958, 899, 874, 754 cm-1; HRMS (EI) m/z calcd for C19H14O2 [M]+ 274.0994; found 274.0992. 1-(2-Benzoyl-5-fluorophenyl)ethanone (4ja): 1H NMR (700 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.50 (dd, J = 8.8, 2.5 Hz, 1H), 7.44–7.42 (m, 3H), 7.30 (t, J = 8.0 Hz, 1H), 2.49 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.8, 196.5, 163.0 (d, JC-F = 251.6 Hz), 140.7 (d, JC-F = 6.2 Hz), 137.0, 136.3 (d, JC-F = 3.1 Hz), 133.2, 130.7 (d, JC-F = 8.0 Hz), 129.4, 128.6, 118.6 (d, JC-F = 21.4 Hz), 116.1 (d, JC-F = 22.6 Hz), 27.8; IR (KBr) υ 1690, 1671, 1600, 1581, 1487, 1406, 1360, 1273, 1192, 1147, 1073, 964, 875, 799, 750 cm-1; HRMS (EI) m/z calcd for C15H11FO2 [M]+ 242.0743; found 242.0748.
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1-(2-Benzoyl-3-fluorophenyl)ethanone (4jb): 1H NMR (700 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.75 (d, J = 7.7 Hz, 1H), 7.58–7.54 (m, 2H), 7.43 (t, J = 7.7 Hz, 2H), 7.37 (t, J = 7.5 Hz, 1H), 2.54 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 196.7 (d, JC-F = 2.1 Hz), 193.5, 160.3 (d, JC-F = 247.1 Hz), 138.4 (d, JC-F = 3.1 Hz), 137.1, 133.4, 130.8 (d, JC-F = 8.0 Hz), 128.8 (d, JC-F = 19.8 Hz), 128.7, 128.6, 125.6 (d, JC-F = 2.5 Hz), 120.5 (d, JC-F = 22.6 Hz), 27.3; IR (KBr) υ 1739, 1678, 1601, 1577, 1452, 1362, 1314, 1270, 932, 889, 799, 758 cm-1; HRMS (EI) m/z calcd for C15H11FO2 [M]+ 242.0743; found 242.0748. 1-(2-Benzoyl-6-fluorophenyl)ethanone (4k): 1H NMR (700 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.57 (t, J = 7.3 Hz, 1H), 7.53–7.50 (m, 1H), 7.45 (t, J = 7.8 Hz, 2H), 7.28 (t, J = 9.1 Hz, 1H), 7.23 (d, J = 7.5 Hz, 1H), 2.60 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.1, 195.9, 160.5 (d, JC-F = 250.0 Hz), 141.7, 136.7, 133.3, 132.1 (d, JC-F = 8.5 Hz), 129.7, 128.6 (d, JC-F = 16.7 Hz), 128.5, 124.9 (d, JC-F = 3.3 Hz), 118.4 (d, JC-F = 23.3 Hz), 31.8 (d, JC-F = 5.4 Hz); IR (KBr) υ 2970, 1738, 1713, 1670, 1451, 1362, 1280, 1055, 1013, 710 cm-1; HRMS (EI) m/z calcd for C15H11FO2 [M]+ 242.0743; found 242.0744. 5-Benzoylchroman-4-one (4l): 1H NMR (700 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.56–7.51 (m, 2H), 7.41 (t, J = 8.1 Hz, 2H), 7.11 (d, J = 8.4 Hz, 1H), 6.90 (d, J = 7.2 Hz, 1H), 4.56 (t, J = 6.3 Hz, 2H), 2.75 (t, J = 6.3 Hz, 2H); 13C NMR (175 MHz, CDCl3) δ 197.3, 190.5, 162.1, 141.8, 136.9, 135.6, 133.0, 129.1, 128.4, 120.2, 119.5, 119.1, 67.0, 37.6; IR (KBr) υ 2833, 1681, 1454, 1114, 1032, 713 cm-1; HRMS (EI) m/z calcd for C16H12O3 [M]+ 252.0786; found 252.0788. 8-Benzoyl-6-methoxy-3,4-dihydronaphthalen-1(2H)-one (4m): 1 H NMR (700 MHz, CDCl3) δ 7.72 (d, J = 8.2 Hz, 2H), 7.48 (t, J = 7.3 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H), 6.80 (s, 1H), 6.67 (s, 1H), 2.97 (t, J = 6.0 Hz, 2H), 2.50 (t, J = 6.7 Hz, 2H), 2.11–2.08 (m, 2H); 13C NMR (175 MHz, CDCl3) δ 197.8, 195.9, 163.0, 147.9, 144.5, 137.1, 132.7, 128.9, 128.4, 124.7, 113.9, 111.9, 55.7, 38.7, 30.4, 23.0; IR (KBr) υ 2938, 1672, 1591, 1454, 1354, 1320, 1277, 1149, 1055, 1007, 719 cm-1; HRMS (EI) m/z calcd for C18H16O3 [M]+ 280.1099; found 280.1100.
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128.4, 114.4, 113.4, 55.8, 26.6; IR (KBr) υ 1679, 1597, 1566, 1451, 1417, 1360, 1319, 1272, 1233, 1122, 1071, 1026, 955, 841, 749 cm-1; HRMS (EI) m/z calcd for C16H14O3 [M]+ 254.0943; found 254.0944.
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1,2-Phenylenebis(phenylmethanone (4n): 1H NMR (700 MHz, CDCl3) δ 7.70 (d, J = 8.2 Hz, 4H), 7.62–7.61 (m, 4H), 7.51 (t, J = 7.3 Hz, 2H), 7.37 (t, J = 7.7 Hz, 4H); 13C NMR (175 MHz, CDCl3) δ 196.6, 140.0, 137.2, 133.0, 130.4, 129.9, 129.7, 128.4; IR (KBr) υ 2832, 1719, 1657, 1525, 1449, 1397, 1318, 1229, 1105, 1027, 938, 805, 764 cm-1; HRMS (EI) m/z calcd for C20H14O2 [M]+ 286.0994; found 286.0989.
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Notes and references 12
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School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Fax: 82 31 292 8800; Tel: 82 31 290 7788; E-mail: [email protected] b Department of Chemistry, Sookmyung Women’s University, Seoul 140742, Republic of Korea. Fax: 82 2 2077 7321; Tel: 82 2 2077 7549; Email: [email protected] † Electronic Supplementary Information (ESI) available: 1H and 13C NMR copies of all products. See DOI: 10.1039/b000000x/ 1 (a) H. Surburg and J. Panten, Common Fragrance and Flavor Materials, 5th ed.; Wiley-VCH: Weinheim, Germany, 2006; (b) Y. Deng, Y.-W. Chin, H. Chai, W. J. Keller and A. D. Kinghorn, J. Nat. Prod., 2007, 70, 2049; (c) K. R. Romines, G. A. Freeman, L. T. Schaller, J. R. Cowan, S. S. Gonzales, J. H. Tidwell, C. W. Andrews, D. K. Stammers, R. J. Hazen, R. G. Ferris, S. A. Short, J. H. Chan and L. R. Boone, J. Med. Chem., 2006, 49, 727; (d) P. J. Masson, D. Coup, J. Millet and N. L. Brown, J. Bio. Chem., 1994, 270, 2662. 2 A. Kotali and P. A. Harris, Org. Prep. Proced. Int., 2003, 35, 583. 3 (a) F. Weygand, H. Weber, E. Maekawa and G. Eberhardt, Chem. Ber., 1956, 89, 1994; (b) M. Roth, Anal. Chem., 1971, 43, 880; (c) L. A. Sternson, J. F. Stobaugh and A. J. Repta, Anal. Biochem., 1985, 144, 233; (d) S. C. Baele, J. C. Savage, D. Wiesler, S. M. Wiedstock and M. Novotny, Anal. Chem., 1988, 60, 1765. 4 H. Ebrahim and K. Dakshinamurti, Anal. Biochem., 1986, 154, 282. 5 (a) A. Kotali and P. G. Tsoungas, Tetrahedron Lett., 1987, 28, 4321; (b) A. Kotali, U. Glaveri, E. Pavlidou and P. G. Tsoungas, Synthesis, 1990, 12, 1172; (c) A. R. Katrizky and A. Kotali, Tetrahedron Lett., 1990, 31, 6781. 6 (a) R. M. Moriarty, B. A. Berglund and M. S. C. Rao, Synthesis, 1993, 318; (b) H. Xian, Z. Qing and Z. Jizheng, Synth. Commun., 2001, 31, 2413; (c) S. Kumar and D. Kumar, Synth. Commun., 2008, 38, 3683. 7 For selected reviews on C–H bond activation, see: (a) L. Ackermann, Chem. Rev., 2011, 111, 1315; (b) S. H. Cho, J. Y. Kim, J. Kwak and S. Chang, Chem. Soc. Rev., 2011, 40, 5068; (c) J. Wencel-Delord, T. Dröge, F. Kiu and F. Glorius, Chem. Soc. Rev., 2011, 40, 4740; (d) O. Baudoin, Chem. Soc. Rev., 2011, 40, 4902; (e) J. L. Bras and J. Muzart, Chem. Rev., 2011, 111, 1170. 8 For selected examples on sp2 C–H acylation using aldehydes, see: (a) X. Jia, S. Zhang, W. Wang, F. Luo and J. Cheng, Org. Lett., 2009, 11, 3120; (b) J. Park, E. Park, A. Kim, Y. Lee, K.-W. Chi, J. H. Kwak, Y. H. Jung and I. S. Kim, Org. Lett., 2011, 13, 4390; (c) S. Sharma, E. Park, J. Park and I. S. Kim, Org. Lett., 2012, 14, 906; (d) S. Sharma, J. Park, E. Park, A. Kim, M. Kim, J. H. Kwak, Y. H. Jung and I. S. Kim, Adv. Synth. Catal., 2013, 355, 332; (e) C.-W. Chan, Z. Zhou, A. S. C. Chan and W.-Y. Yu, Org. Lett., 2010, 12, 3926; (f) Y. Yang, B. Zhou and Y. Li, Adv. Synth. Catal., 2012, 354, 2916; For selected examples on sp2 C–H acylation using alcohols, see: (g) F. Xiao, Q. Shuai, F. Zhao, O. Baslé, G. Deng and C.-J. Li, Org. Lett., 2011, 13, 1614; (h) J. Park, A. Kim, S. Sharma, M. Kim, E. Park, Y. Jeon, Y. Lee, J. H. Kwak, Y. H. Jung and I. S. Kim, Org. Biomol. Chem., 2013, 11, 2766; (i) M. Kim, S. Sharma, J. Park, M. Kim, Y. Choi, Y. Jeon, J. H. Kwak and I. S. Kim, Tetrahedron, 2013, 69, 6552.. 9 For selected examples on sp2 C–H acylation using α-oxocarboxylic acids, see: (a) P. Fang, M. Li and H. Ge, J. Am. Chem. Soc., 2010, 132, 11898; (b) M. Li and H. Ge, Org. Lett., 2010, 12, 3464; (c) H. Wang, L.-N. Guo and X.-H. Duan, Org. Lett., 2012, 14, 4358; (d) M. Kim, J. Park, S. Sharma, A. Kim, E. Park, J. H. Kwak, Y. H. Jung and I. S. Kim, Chem. Commun., 2013, 49, 925; (e) J. Park, M. Kim, S. Sharma, E. Park, A. Kim, S. H. Lee, J. H. Kwak, Y. H. Jung and I. S.
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Kim, Chem. Commun., 2013, 49, 1654; (f) S. Sharma, A. Kim, E. Park, J. Park, M. Kim, J. H. Kwak, S. H. Lee, Y. H. Jung and I. S. Kim, Adv. Synth. Catal., 2013, 355, 667; (g) L.Yu, P. Li and L. Wang, Chem. Commun., 2013, 49, 2368. (a) S. Guin, S. K. Rout, A. Banerjee, S. Nandi and B. K. Patel, Org. Lett., 2012, 14, 5294; (b) Y. Wu, P. Y. Choy, F. Mao and F. Y. Kwong, Chem. Commun., 2013, 49, 689. For recent reviews, see: (a) J. Barluenga and C. Valdés, Angew. Chem., Int. Ed., 2011, 50, 7486; (b) Y. Zhang and J. B. Wang, Eur. J. Org. Chem., 2011, 1015; (c) H. B. Zhang and Z. H. Shao, Chem. Soc. Rev., 2012, 41, 560. (a) K. Inamoto, T. Saito, M. Katsuno, T. Sakamoto and K. Hiroya, Org. Lett., 2007, 9, 2931; (b) G. Li, Z. Ding and B. Xu, Org. Lett., 2012, 14, 5338; (c) G. Zhang, J. Miao, Y. Zhao and H. Ge, Angew, Chem., Int. Ed., 2012, 51, 8318. B. X. Mi, P. F. Pang, Z. Q. Gao, C. S. Lee, S. T. Lee, H. L. Hong, X. M. Chen, M. S. Wong, P. F. Xia, K. W. Cheah, C. H. Chen and W. Huang, Adv. Mater., 2009, 21, 339. (a) R. J. Austin, J. Kaizerman, B. Lucas, D. L. McMinn and J. Powers, PCT Int. App. WO 2009002469, 2008; (b) A. Tasker, D. Zhang, L. H. Pettus, R. M. Rzasa, K. K. C. Sham, S. Xu and P. P. Chakrabarti, PCT Int. App. WO 2008030466, 2008. For a review on palladacycles, see: J. Dupont, C. S. Consorti and J. Spencer, Chem. Rev., 2005, 105, 2527. For a review of acyl radicals, see: (a) C. Chatgilialoglu, D. Crich, M. Komatsu and I. Ryu, Chem. Rev., 1999, 99, 1991; For recent selected examples of acyl radicals, see: (b) Z. Shi and F. Glorius, Chem. Sci., 2013, 4, 829; (c) Z. Liu, J. Zhang, S. Chen, E. Shi, Y. Xu and X. Wan, Angew. Chem., Int. Ed., 2012, 51, 3231. For a selected example for Pd(III) intermediate, see: (a) S. R. Neufeldt and M. S. Sanford, Adv. Synth. Catal., 2012, 354, 3517; For selected examples for Pd(IV) intermediate, see: (b) A. J. Hickman and M. S. Sanford, Nature, 2012, 484, 177; (c) K. Muñiz, Angew. Chem., Int. Ed., 2009, 48, 9412; (d) P. L. Arnold, M. S. Sanford and S. M. Pearson, J. Am. Chem. Soc., 2009, 131, 13912; (e) J. M. Racowski, A. R. Dick and M. S. Sanford, J. Am. Chem. Soc., 2009, 131, 10974. J. D. Knight, J. B. Brown, J. S. Overby, C. F. Beam and N. D. Camper, J. Heterocyclic Chem., 2008, 45, 189.
Journal Name, [year], [vol], 00–00 | 7
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DOI: 10.1039/C3OB41644E
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Pd(II)-catalyzed direct C–H acylation of N-Boc hydrazones with aldehydes: one-pot synthesis of 1,2-diacylbenzenes Satyasheel Sharma,a Aejin Kim,a Jihye Park,a Mirim Kim,a Jong Hwan Kwak,a Young Hoon Jung,a Jung Su Park,b,* and In Su Kima,* 5
10
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX DOI: 10.1039/b000000x A palladium(II)-catalyzed direct acylation of acetophenone N-Boc hydrazones with aldehydes via C–H bond activation is described. This protocol provides direct access to a range of 1,2-diacylbenezenes, which are useful precursors to construct biologically interesting and pharmaceutically important compounds.
Introduction
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Aryl ketones are important structural scaffolds found in natural products, medicinally relevant molecules, and functional materials.1 Notably, 1,2-diacylbenzenes are known to be crucial synthetic precursors due to the high prevalence of biologically active compounds and pharmaceuticals such as phthalazines, Narylphthalimidines, isobenzofurans, indanones, isoindoles, isoindolines, and isoquinolines.2 Also, 1,2-diacylbenzenes are receiving increasing attention as fluorescence reagents for both qualitative and quantitative high-sensitivity analysis for amino acids and peptides.3 In particular, 1,2-diacylbenzenes were used in a fluorometric assay for biotinase due to their ability to react selectively with lysine.4 These facts have led to develop an efficient method for the preparation of 1,2-diacylbenzenes. General methods for the construction of 1,2-diacylbenzenes include oxidation of N-aroylhydrazones of o-hydroxyaryl ketone acylhydrazones with lead tetraacetate5 or hypervalent iodine reagents.6 However, from a synthetic point of view, all these reactions present intrinsic drawbacks, which include the use of toxic reagents, poor functional group tolerance, harsh reaction conditions, and the requirement of prefunctionalized starting materials. Therefore, it is highly desirable to develop atomeconomical protocols that involve fewer synthetic steps and readily available starting materials for the preparation of 1,2diacylbenzenes. Transition metal-catalyzed dehydrogenative cross-coupling reactions via selective C–H bond activation have emerged as a powerful tool to produce structurally diverse organic molecules, because such methods avoid a preparation of preactivated starting materials and a production of stoichiometric metallic waste.7 Thus, cross-coupling reactions via C–H bond activation can lead to an improved overall efficiency of the desired transformation. Recently, transition metal-catalyzed oxidative acylations of inactive sp2 C–H bonds with aldehydes and alcohols as acyl sources have been described.8 Catalytic decarboxylative acylations of aromatic C–H bonds using α-oxocarboxylic acids as This journal is © The Royal Society of Chemistry [year]
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acyl surrogates were also reported.9 In addition, a palladiumcatalyzed acylation of 2-arylpyridines and acetanilides via oxidation of benzylic C–H bonds in toluene derivatives was demonstrated.10 Notably, Yu8e and Li8f respectively disclosed efficient ways to prepare ortho-acylated acetophenone O-methyl oximes as the precursors for 1,2-diacylbenzenes via palladiumand rhodium-catalyzed oxidative coupling reactions between acetophenone O-methyl oximes and aldehydes. However, these approaches are required an additional step to remove the oxime directing group for the preparation of 1,2-diacylbenzenes. Ph cat. Pd(OAc)2 Cu(OAc)2, AgO2CCF3 Ph NNHTs
N N Ts ref. 12a Ph
cat. [RhCp*Cl2]2 Cu(OAc)2•H2O
H
H
N N
Ts
CO2R CO2R ref. 12b
Me N
R cat.CuSO4, CuI
N H
H
N
N R
Pyridine, TFA, O2, DMF ref. 12c Me
Me NNHBoc
cat. Pd(OAc)2, TBHP O
H H
R
O O R this work
Figure 1 Hydrazone directing groups in C–H bond activation.
60
65
Hydrazones are common protection groups of the ketone moiety, and have become versatile cross-coupling partners in transition metal-catalyzed reactions.11 However, hydrazones have been rarely used as directing groups of C–H bond activation protocols.12 For examples, Inamoto and Hiroya described a Pdcatalyzed C–H activation of N-tosylhydrazones followed by intramolecular amination to afford highly substituted indazoles (Figure 1).12a Xu and coworkers reported a Rh-catalyzed tandem C–H olefination and annulations between sulfonylhydrazones and
[journal], [year], [vol], 00–00 | 1
Organic & Biomolecular Chemistry Accepted Manuscript
ARTICLE TYPE
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DOI: 10.1039/C3OB41644E
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10
15
20
25
30
50
Table 1 Selected optimization of reaction conditionsa
Results and discussion Our initial investigation focused on the coupling of p-CF3acetophenone N-substituted hydrazones with benzaldehyde to afford 1,4-disubstituted phthalazines with interesting luminescent13 and anticancer activities14 by tandem acylation and intramolecular cyclization (Scheme 1, eq. 1). After extensive screening of hydrazones with =NNH-Boc, =NNH-H, =NNH-Moc and =NNH-Ts directing groups, all reactions provide a mixture of p-CF3-acetophenone, acylated hydrazones and 1,2diacylbenzenes, instead of the phthalazine compounds (Scheme 1, eqs. 2 and 3). Interestingly, p-CF3-acetophenone N-Boc hydrazone (1a) was found to couple with 2 equiv. of benzaldehyde (2a) in the presence of 10 mol % of Pd(OAc)2 and 3 equiv. of TBHP in DCE solvent at 70 oC for 10 h to afford 1,2diacylbenzene 3a in 58% yield (Table 1, entry 1). Thus, hydrazone derivative 1a was chosen as an optimal substrate for the preparation of 1,2-diacylbenzene product. Me N F3C
H N
O R
+
H
Ph
H
acylation & annulation (eq. 1)
acylation & hydrolysis (eq. 3)
acylation
60
(eq. 2) Me
Me Me
N N
F3C Ph
F3C
N O
H N
R F3C
O O Ph
Ph
65
Scheme 1 Catalytic acylation strategy of hydrazone directing groups.
40
45
Screening of oxidants showed that TBHP is superior to other oxidants such as (PhCOO)2, Ag2O and (NH4)2S2O8 (Table 1, entries 2–4). Further screening of the effect of palladium revealed that Pd(OAc)2 was found to be most effective in this coupling reaction (Table 1, entries 5 and 6). After screening of solvents under otherwise identical conditions, DCE was found to be the most effective solvent in this coupling reaction, whereas other solvents such as toluene, THF, MeCN and DMF failed to facilitate high levels of conversion (Table 1, entries 7–10). Further study showed that AcOH additive displayed the decreased catalytic activity (Table 1, entry 11). Logically, it was thought that the formation of 3a can be controlled by the amount of catalyst, oxidant and aldehyde (Table 1, entries 12–14). Indeed, 2 | Journal Name, [year], [vol], 00–00
Entry
Pd catalyst (mol %)
Oxidant (equiv.)
Solvent
Yield (%)b
1
Pd(OAc)2 (10)
TBHP (3)
DCE
58
2
Pd(OAc)2 (10)
(PhCOO)2 (3)
DCE
24
3
Pd(OAc)2 (10)
Ag2O (3)
DCE
N.R.
4
Pd(OAc)2 (10)
(NH4)2S2O8 (3)
DCE
N.R.
5
Pd(TFA)2 (10)
TBHP (3)
DCE
28
6
PdCl2 (10)
TBHP (3)
DCE
22
7
Pd(OAc)2 (10)
TBHP (3)
toluene
46
8
Pd(OAc)2 (10)
TBHP (3)
THF
24
9
Pd(OAc)2 (10)
TBHP (3)
MeCN
51
10
Pd(OAc)2 (10)
TBHP (3)
DMF
N.R.
11c
Pd(OAc)2 (10)
TBHP (3)
DCE
50
12
Pd(OAc)2 (10)
TBHP (4)
DCE
63
13
Pd(OAc)2 (5)
TBHP (4)
DCE
48
14d
Pd(OAc)2 (10)
TBHP (4)
DCE
71
15d,e
Pd(OAc)2 (10)
TBHP (4)
DCE
N.R.
a 55
35
the use of 3 equiv. of benzaldehyde (2a) and 4 equiv. of TBHP afforded our desired product 3a in high yield (71%), as shown in entry 14. In addition, this coupling reaction did not proceed at room temperature, even for longer reaction time (Table 1, entry 15).
70
75
Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), Pd catalyst (quantity noted), oxidant (quantity noted), solvent (1 mL) at 70 oC for 10 h in pressure tubes. b Isolated yield by flash column chromatography. c AcOH (50 mol %) was added as an additive. d 2a (0.9 mmol, 3 equiv.). e Room temperature, 20 h.
With the optimized reaction conditions in hand, the scope and limitation of the aldehyde were examined, as shown in Table 2. The coupling of p-CF3-acetophenone N-Boc hydrazone (1a) and aldehydes 2b–2g with electron-donating (OMe, OBn and Me) and electron-withdrawing groups (CF3, F and Cl) at the paraposition on the aromatic ring was found to be favored in the acylation reaction to afford the corresponding products 3b–3g in moderate to high yields. In addition, meta-substituted benzaldehydes 2h–2j smoothly underwent this coupling reaction to generate the corresponding products. Notably, omethoxybenzaldehyde 2k and o-fluoro-p-methoxybenzaldehyde 2l proved to be good substrates for this transformation, affording the corresponding products 3k and 3l. However, heterocyclic benzaldehydes and aliphatic aldehydes failed to deliver the coupling products with the current catalytic system. To further explore the substrate scope and limitations of this process, a broad range of acetophenone or benzophenone N-Boc hydrazones 1b–1m was screened to couple with benzaldehyde (2a), as shown in Table 3.
This journal is © The Royal Society of Chemistry [year]
Organic & Biomolecular Chemistry Accepted Manuscript
5
alkenes to give 1,2-dihydrophthalazines.12b Recently, Ge et al. disclosed a Cu-catalyzed dehydrogenative intramolecular cyclization of N-methyl-N-phenylhydrazones to provide cinnolines.12c As part of an ongoing research program directed toward the development of catalytic acylation reactions of inactive C–H bonds, we became interested in developing an efficient synthetic route to 1,2-diacylbenzenes via C–H bond activation. Herein we present the tandem palladium-catalyzed ortho-acylation and deprotection of acetophenone N-Boc hydrazones with aldehydes under tert-butyl hydroperoxide (TBHP) as a convenient oxidant to afford 1,2-diacylbenzenes. To the best of our knowledge, it is the first report of direct catalytic acylation for the formation of 1,2-diacylbenzenes.
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Table 2 Scope of aldehydesa Me
Me
F3C
+
R
H
H 1a
o
DCE, 70 C, 10 h
Me
O O
R 3a-3l (%)b
F3C
Me
O O
F3C
O O
F3C
2a-2l
Me
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Pd(OAc)2 (10 mol %) TBHP (4 equiv.)
O
NNHBoc
O O
F3C
20
Me O O
F3C
25
OMe 3b (69%)
3a (71%) Me O O
F3C
OBn 3c (61%)
Me
CF3
O O
F3C
F
3e (55%)
Me
Me
O O
F3C
Me 3d (50%)
Cl 3g (63%)
3f (72%)
O O
F3C
30
3h (60%) 35
Me
Me
O O
F3C
Me
O O
F3C
Me
F3C
O O
O O
F3C
F
OMe OMe 3i (55%)
Cl 3j (48%)
40
Cl 3k (55%)
OMe 3l (67%)
a 5
Reaction conditions: 1a (0.3 mmol), 2a–2l (0.9 mmol), Pd(OAc)2 (10 mol %), TBHP (1.2 mmol), DCE (1 mL) at 70 oC for 10 h in pressure tubes. b Isolated yield by flash column chromatography.
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Table 3 Scope of acetophenone N-Boc hydrazonesa 50
found to be favored in the acylation reaction to afford the corresponding products 4b–4g in good yields. Notably, the bromo and chloro moieties on the aromatic ring were tolerated under these coupling conditions and offers versatile synthetic functionality for further elaboration. The reaction of metasubstituted acetophenone N-Boc hydrazones 1h and 1i preferentially occurred at the less hindered position to afford the corresponding product 4h and 4i in good yields as a single regioisomer. However, fluoro-substituted acetophenone N-Boc hydrazone 1j at the meta-position furnished the acylated products 4ja and 4jb in 50% yield, providing the regioisomers at C6 and C2 with 2:1 ratio. These data suggest that the steric effect of the substrates strongly interferes with either the formation of the cyclopalladated intermediate or the proximity of the acyl radical into the cyclopalladated intermediate. The ortho-substituted acetophenone N-Boc hydrazones 1k–1m were also found to be favored in this catalyst system. In addition, benzophenone N-Boc hydrazone (1n) was smoothly converted to the corresponding product 4n in 40% yield. Some control experiments were performed to obtain a mechanistic insight. Treatment of 4-fluoroacetophenone (5a) and benzaldehyde (2a) under standard reaction conditions provided no formation of our desired product 4f (Scheme 2, eq. 1). This result indicates that the hydrazone directing group can initiate ortho-selective cyclopalladation on the arene ring by Pd(OAc)2 prior to the cleavage of hydrazone group. 4-Fluoroacetophenone N-Boc hydrazones (1f) was hydrolyzed to the corresponding acetophenone 5a in the presence of TBHP irrespective of whether Pd(OAc)2 was present or not, thus suggesting that hydrazone directing group might be cleaved by TBHP (Scheme 2, eqs. 2 and 3). However, in the presence of aldehyde 2a under standard reacton conditions for 2 h, the reaction furnished the drastically increased formation of our desired product 4f and the reaction intermediate hydrazone 6a (Scheme 2, eq. 4). This observation suggests that the rate of acylation process is significantly faster than those of the hydrolysis of hydrazone group. Me
Me O
+
H
H
F
standard conditions
O
5a
Ph
O O
F
10 h
(eq. 1)
Ph 4f (not observed)
2a Me NNHBoc
F
TBHP (4 equiv.)
1f
H
+ 5a
(eq. 2)
ratio = 60:40 by crude NMR analysis
DCE, 70 oC 2h
1f standard conditions
1f
1f
1f
1f
10
15
Reaction conditions: 1b–1n (0.3 mmol), 2a (0.9 mmol), Pd(OAc)2 (10 mol %), TBHP (1.2 mmol), DCE (1 mL) at 70 oC for 10 h in pressure tubes. b Isolated yield by flash column chromatography.
This journal is © The Royal Society of Chemistry [year]
+ 5a
+
4f
NNHBoc O
+ F
(eq. 4)
Ph ratio = 27:18:44:11 by crude NMR analysis
a
The coupling of benzaldehyde (2a) and acetophenone N-Boc hydrazones 1b–1g with electron-rich and electron-deficient groups (OMe, Br, Cl, F and NO2,) at the para-positions was
2h
(eq. 3)
Me
standard conditions
+ 2a
+ 5a
ratio = 35:75 by crude NMR analysis
2h
6a
Scheme 2 Control experiments. 55
On the basis of these collective data, a plausible mechanism is proposed as illustrated in Scheme 3. First, a coordination of the N atom of 1b to Pd(II) and the subsequent directed cyclopalladation Journal Name, [year], [vol], 00–00 | 3
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General procedure for the synthesis of acetophenone N-Boc hydrazones: Acetophenone N-Boc hydrazones were synthesized according to the procedure reported in the literature.18 45
50
55
60
10
Scheme 3 Plausible reaction mechanism.
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Typical procedure for the acylation of N-Boc hydrazones (3a– l and 4b–m): To an oven-dried sealed tube with p-CF3acetophenone N-Boc hydrazone (1a) (90.6 mg, 0.3 mmol, 100 mol %), Pd(OAc)2 (6.7 mg, 0.03 mmol, 10 mol %), benzaldehyde (2a) (95.4 mg, 0.9 mmol, 300 mol %) in anhydrous DCE (1 mL) was added TBHP (0.22 mL, 1.2 mmol, 400 mol %, 5.5 M in decane). The reaction mixture was allowed to stir at 70 ºC for 10 h. After cooling at room temperature, the reaction mixture was evaporated onto silica gel. Purification of the product by flash column chromatography (SiO2: n-hexanes/EtOAc) provided the corresponding product 3a (62.2 mg) in 71% yield. 1-(2-Benzoyl-4-(trifluoromethyl)phenyl)ethanone (3a): 1H NMR (700 MHz, CDCl3) δ 7.97 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.67 (s, 1H), 7.58 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 8.0 Hz, 2H), 2.55 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.9, 196.0, 141.3, 140.8, 136.4, 133.6 (q, JC-F = 33.4 Hz), 133.5, 129.5, 129.4, 128.7, 126.8 (q, JC-F = 3.8 Hz), 125.3 (q, JC-F = 3.1 Hz), 123.1 (q, JC-F = 272.8 Hz), 27.8; IR (KBr) υ 2854, 1738, 1694, 1674, 1451, 1366, 1315, 1262, 1177, 1132, 1089, 750 cm-1; HRMS (EI) m/z calcd for C16H11F3O2 [M]+ 292.0711; found 292.0709.
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In conclusion, a hydrazone-directed Pd-catalyzed ortho-acylation of acetophenone N-Boc hydrazones with aldehydes has been developed, which is an effective approach to direct access of various 1,2-diacylbenzenes. These transformations have been applied to a wide range of substrates, and typically proceed with excellent level of chemoselectivity as well as with high functional group tolerance. Further applications of this method to the synthesis of biologically active compounds are in progress.
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Experimental General Methods: Commercially available reagents were used without additional purification, unless otherwise stated. Sealed tubes (13 × 100 mm2) were purchased from Fischer Scientific and dried in oven for overnight and cooled under a stream of nitrogen prior to use. Thin layer chromatography was carried out using plates coated with Kieselgel 60F254 (Merck). For flash column chromatography, E. Merck Kieselgel 60 (230-400 mesh) was used. Nuclear magnetic resonance spectra (1H and 13C NMR) were recorded on a Bruker Unity 400 MHz and 700 MHz spectrometer for CDCl3 solutions and chemical shifts are reported as parts per million (ppm) relative to, respectively, residual CHCl3 δH (7.24 ppm) and CDCl3 δC (77.2 ppm) as internal standards. Resonance patterns are reported with the notations s (singlet), d (doublet), t (triplet), q (quartet), and m (multiplet). In addition, the notation br is used to indicate a broad signal. Coupling constants (J) are reported in hertz (Hz). IR spectra were recorded on a Varian 2000 Infrared spectrophotometer and are reported as cm-1. High-resolution mass spectra (HRMS) were recorded on a JEOL JMS-600 spectrometer. 4 | Journal Name, [year], [vol], 00–00
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1-(2-(4-Methoxybenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3b): 1H NMR (700 MHz, CDCl3) δ 7.93 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.65 (s, 1H), 6.93 (d, J = 8.9 Hz, 2H), 3.86 (s, 3H), 2.54 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.2, 194.7, 163.9, 141.5, 140.9, 133.4 (q, JC-F = 33.2 Hz), 131.9, 129.4, 129.3, 126.5 (q, JC-F = 3.7 Hz), 125.3 (q, JC-F = 3.6 Hz), 123.2 (q, JC-F = 272.4 Hz), 114.0, 55.5, 28.1; IR (KBr) υ 2833, 1717, 1680, 1640, 1525, 1451, 1289, 1223, 1148, 1105, 1031, 805, 746 cm-1; HRMS (EI) m/z calcd for C17H13F3O3 [M]+ 322.0817; found 322.0825. 1-(2-(4-(Benzyloxy)benzoyl)-4(trifluoromethyl)phenyl)ethanone (3c): 1H NMR (700 MHz, CDCl3) δ 7.94 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 8.9 Hz, 2H), 7.65 (s, 1H), 7.43–7.34 (m, 4H), 7.35–7.34 (m, 1H), 7.02 (d, J = 8.9 Hz, 2H), 5.13 (s, 2H), 2.54 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.4, 194.7, 163.1, 141.5, 140.9, 136.0, 133.4 (q, JC-F = 33.0 Hz), 131.9, 129.6, 129.3, 128.7, 128.3, 127.5, 126.6 (q, JC-F = 3.8 Hz), 125.3 (q, JC-F = 3.2 Hz), 123.2 (q, JC-F = 273.0 Hz), 114.8, 70.2, 28.1; IR (KBr) υ 1739, 1665, 1599, 1573, 1455, 1423, 1367, 1338, 1257, 1172, 1133, 1089, 765 cm-1; HRMS (EI) m/z calcd for C23H17F3O3 [M]+ 398.1130; found 398.1130. 1-(2-(4-Methylbenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3d): 1H NMR (700 MHz, CDCl3) δ 7.95 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.65 (s, 1H), 7.63 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.5 Hz, 2H), 2.54 (s, 3H), 2.41 (s, 3H), 3.60 (s, 3H); 13 C NMR (175 MHz, CDCl3) δ 198.1, 195.8, 144.6, 141.5, 140.9, 133.9, 133.5 (q, JC-F = 31.9 Hz), 129.6, 129.4, 129.3, 126.7 (q, JCThis journal is © The Royal Society of Chemistry [year]
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provides a 5-membered palladacycle I.15 At the same time, the tBuO· radical generated from TBHP can abstract H atom from the aldehyde to give a reactive acyl radical.16 The palladacycle I can react with a benzoyl radical to afford the dimeric Pd(III) or Pd(IV) intermediate II,17 which can undergo reductive elimination to afford the acylated hydrazone III and regenerate Pd(II) catalyst. Finally, the acylated hydrazone III is rapidly converted to our desired 1,2-diacylbenzene 4b by TBHP.
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1-(4-(Trifluoromethyl)-2-(4(trifluoromethyl)benzoyl)phenyl)ethanone (3e): 1H NMR (700 MHz, CDCl3) δ 8.04 (d, J = 8.1 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 8.1 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H), 7.65 (s, 1H), 2.58 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.4, 195.0, 141.0, 140.1, 139.2, 134.4 (q, JC-F = 21.8 Hz), 134.3 (q, JC-F = 17.5 Hz), 129.9, 127.2 (q, JC-F = 3.1 Hz), 127.0, 125.8 (q, JC-F = 3.9 Hz), 125.1 (q, JC-F = 3.0 Hz), 123.0 (q, JC-F = 271.7 Hz), 122.7 (q, JC-F = 271.5 Hz), 27.4; IR (KBr) υ 2947, 2833, 1721, 1680, 1639, 1525, 1451, 1325, 1290, 1217, 1148, 1107, 1032, 741 cm-1; HRMS (EI) m/z calcd for C17H10F6O2 [M]+ 360.0585; found 360.0580. 1-(2-(4-Fluorobenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3f): 1H NMR (700 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.76–7.74 (m, 2H), 7.64 (s, 1H), 7.13–7.11 (m, 2H), 2.57 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.7, 194.6, 165.8 (d, JC-F = 254.6 Hz), 141.2, 140.4, 133.8 (q, JC-F = 33.8 Hz), 132.9, 132.0 (d, JC-F = 9.2 Hz), 129.7, 126.9 (q, JC-F = 4.2 Hz), 125.1 (q, JC-F = 3.6 Hz), 123.1 (q, JC-F = 271.3 Hz), 115.9 (d, JC-F = 22.6 Hz), 27.7; IR (KBr) υ 1693, 1674, 1599, 1505, 1409, 1362, 1300, 1261, 1178, 1134, 1089, 1014, 967, 906, 851, 766 cm-1; HRMS (EI) m/z calcd for C16H10F4O2 [M]+ 310.0617; found 310.0605.
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NMR (175 MHz, CDCl3) δ 197.8, 195.9, 159.9, 141.4, 140.7, 137.8, 133.7 (q, JC-F = 33.1 Hz), 129.7, 129.6, 129.4, 126.8 (q, JCF = 2.9 Hz), 125.4 (q, JC-F = 2.9 Hz), 123.9 (q, JC-F = 271.5 Hz), 122.4, 120.2, 55.5, 27.8; IR (KBr) υ 1739, 1694, 1597, 1582, 1487, 1432, 1366, 1336, 1270, 1218, 1176, 1131, 1089, 1045, 970, 908, 840, 792 cm-1; HRMS (EI) m/z calcd for C17H13F3O3 [M]+ 322.0817; found 322.0817. 1-(2-(3,5-Dichlorobenzoyl)-41 (trifluoromethyl)phenyl)ethanone (3j): H NMR (700 MHz, CDCl3) δ 8.06 (d, J = 8.1 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.62 (s, 1H), 7.54–7.53 (m, 3H), 2.60 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.2, 193.6, 140.5, 139.7, 139.1, 135.7, 134.5 (q, JC-F = 33.2 Hz), 133.0, 130.1, 127.3 (q, JC-F = 3.1 Hz), 127.2, 125.0 (q, JC-F = 3.8 Hz), 123.7 (q, JC-F = 271.5 Hz), 27.3; IR (KBr) υ 2946, 2833, 1717, 1681, 1638, 1567, 1415, 1326, 1291, 1233, 1163, 1144, 1026, 875, 802, 758 cm-1; HRMS (EI) m/z calcd for C16H9Cl2F3O2 [M]+ 359.9932; found 359.9931. 1-(2-(2-Methoxybenzoyl)-4-(trifluoromethyl)phenyl)ethanone 1 (3k): H NMR (700 MHz, CDCl3) δ 7.78–7.74 (m, 3H), 7.60 (s, 1H), 7.55–7.52 (m, 1H), 7.08 (t, J = 8.4 Hz, 1H), 6.95 (d, J = 8.3 Hz, 1H), 3.59 (s, 3H), 2.51 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 200.0, 194.8, 158.8, 142.3, 142.2, 134.6, 132.6 (q, JC-F = 33.0 Hz), 131.5, 128.2, 126.8 (q, JC-F = 3.7 Hz), 126.1, 125.4 (q, JC-F = 3.4 Hz), 124.1 (q, JC-F = 271.3 Hz), 121.0, 112.1, 55.5, 28.7; IR (KBr) υ 2946, 2833, 1716, 1680, 1642, 1525, 1450, 1399, 1324, 1292, 1237, 1161, 1106, 1020, 804, 759 cm-1; HRMS (EI) m/z calcd for C17H13F3O3 [M]+ 322.0817; found 322.0817.
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1-(2-(4-Chlorobenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3g): 1H NMR (700 MHz, CDCl3) δ 8.00 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.65 (d, J = 8.6 Hz, 2H), 7.64 (s, 1H), 7.42 (d, J = 8.6 Hz, 2H), 2.57 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.6, 194.9, 141.1, 140.3, 140.0, 134.9, 133.9 (q, JC-F = 33.1 Hz), 130.6, 129.7, 129.1, 127.0 (q, JC-F = 3.0 Hz), 125.1 (q, JC-F = 3.9 Hz), 123.1 (q, JC-F = 271.1 Hz), 27.6; IR (KBr) υ 1730, 1693, 1588, 1488, 1366, 1335, 1260, 1175, 1133, 1090, 966, 905, 845, 751 cm-1; HRMS (EI) m/z calcd for C16H10ClF3O2 [M]+ 326.0321; found 326.0329. 1-(2-(2-Naphthoyl)-4-(trifluoromethyl)phenyl)ethanone (3h): 1 H NMR (700 MHz, CDCl3) δ 8.05 (s, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.97–7.95 (m, 1H), 7.94–7.92 (m, 1H), 7.89 (t, J = 8.1 Hz, 2H), 7.84 (d, J = 8.1 Hz, 1H), 7.74 (s, 1H), 7.60 (t, J = 8.1 Hz, 1H), 7.52 (t, J = 8.1 Hz, 1H), 2.55 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.9, 196.1, 141.5, 140.9, 135.8, 134.6, 133.9, 133.7 (q, JC-F = 33.1 Hz), 132.4, 131.6, 129.6, 129.5, 128.8, 127.9, 126.9, 126.8 (q, JC-F = 3.3 Hz), 125.5 (q, JC-F = 3.8 Hz), 124.5, 123.9 (q, JC-F = 271.5 Hz), 27.9; IR (KBr) υ 2923, 2852, 1737, 1693, 1626, 1576, 1491, 1433, 1359, 1335, 1262, 1199, 1132, 1088, 1019, 964, 905, 866, 801, 777 cm-1; HRMS (EI) m/z calcd for C20H13F3O2 [M]+ 342.0868; found 342.0867. 1-(2-(3-Methoxybenzoyl)-4-(trifluoromethyl)phenyl)ethanone (3i): 1H NMR (700 MHz, CDCl3) δ 7.97 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.41–7.40 (m, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.13–7.11 (m, 2H), 3.85 (s, 3H), 2.55 (s, 3H); 13C
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1-(2-(2-Fluoro-4-methoxybenzoyl)-4(trifluoromethyl)phenyl)ethanone (3l): 1H NMR (700 MHz, CDCl3) δ 7.92 (t, J = 8.6 Hz, 2H), 7.80 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 6.81 (dd, J = 8.8, 2.4 Hz, 1H), 6.53 (dd, J = 12.7, 2.3 Hz, 1H), 3.85 (s, 3H), 2.57 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.2, 191.5, 165.4 (d, JC-F = 11.3 Hz), 164.0 (d, JC-F = 255.1 Hz), 144.4, 139.8, 133.6 (q, JC-F = 33.0 Hz), 132.6 (d, JC-F = 2.5 Hz), 129.3, 126.5 (d, JC-F = 3.2 Hz), 124.4, 124.0 (q, JC-F = 271.4 Hz), 117.8 (d, JC-F = 10.1 Hz), 111.0, 101.8 (d, JC-F = 26.0 Hz), 56.0, 27.7; IR (KBr) υ 1777, 1681, 1615, 1527, 1439, 1394, 1325, 1288, 1229, 1161, 1100, 1063, 999, 941, 816, 760 cm-1; HRMS (EI) m/z calcd for C17H12F4O3 [M]+ 340.0723; found 340.0726. 1-(2-Benzoylphenyl)ethanone (4b): 1H NMR (700 MHz, CDCl3) δ 7.88 (d, J = 7.6 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.53 (t, J = 7.3 Hz, 1H), 7.42–7.40 (m, 3H), 2.51 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.5, 197.8, 140.9, 137.5, 137.2, 133.0, 132.2, 129.7, 129.3, 129.2, 128.5, 128.3, 27.4; IR (KBr) υ 1682, 1596, 1571, 1481, 1449, 1359, 1314, 1267, 1153, 1073, 960, 930, 762 cm-1; HRMS (EI) m/z calcd for C15H12O2 [M]+ 224.0837; found 224.0837. 1-(2-Benzoyl-4-methoxyphenyl)ethanone (4c): 1H NMR (700 MHz, CDCl3) δ 7.73 (d, J = 8.3 Hz, 2H), 7.51 (t, J = 7.3 Hz, 2H), 7.40 (t, J = 8.1 Hz, 2H), 7.03 (dd, J = 8.7, 2.5 Hz, 1H), 6.85 (s, 1H), 3.87 (s, 3H), 2.46 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.5, 196.1, 163.0, 143.9, 137.0, 132.9, 131.9, 129.3, 129.1,
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= 4.1 Hz), 125.3 (q, JC-F = 4.0 Hz), 123.2 (q, JC-F = 270.9 Hz), 28.0, 21.8; IR (KBr) υ 2946, 2832, 1716, 1679, 1637, 1526, 1451, 1408, 1327, 1295, 1235, 1143, 1104, 1036, 790 cm-1; HRMS (EI) m/z calcd for C17H13F3O2 [M]+ 306.0868; found 306.0869. F
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1-(2-Benzoyl-4-bromophenyl)ethanone (4d): 1H NMR (700 MHz, CDCl3) δ 7.76–7.71 (m, 4H), 7.55 (t, J = 7.4 Hz, 1H), 7.52 (s, 1H), 7.43 (t, J = 8.1 Hz, 2H), 2.49 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.2, 196.0, 142.8, 136.6, 136.0, 133.3, 132.7, 131.2, 130.7, 129.3, 128.6, 127.5, 27.3; IR (KBr) υ 1684, 1582, 1554, 1449, 1424, 1360, 1314, 1287, 1266, 1179, 1158, 1094, 1025, 962, 886, 825, 766 cm-1; HRMS (EI) m/z calcd for C15H11BrO2 [M]+ 301.9942; found 301.9938. 1-(2-Benzoyl-4-chlorophenyl)ethanone (4e): 1H NMR (700 MHz, CDCl3) δ 7.82 (d, J = 8.3 Hz, 1H), 7.72 (d, J = 8.3 Hz, 2H), 7.56–7.54 (m, 2H), 7.43 (t, J = 8.2 Hz, 2H), 7.37 (s, 1H), 2.50 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.0, 196.1, 142.7, 139.0, 136.6, 135.5, 133.3, 130.7, 129.7, 129.2, 128.6, 128.4, 27.3; IR (KBr) υ 1684, 1588, 1557, 1449, 1424, 1360, 1314, 1266, 1159, 1074, 964, 887, 809, 746 cm-1; HRMS (EI) m/z calcd for C15H11ClO2 [M]+ 258.0448; found 258.0455. 1-(2-Benzoyl-4-fluorophenyl)ethanone (4f): 1H NMR (700 MHz, CDCl3) δ 7.93 (dd, J = 8.6, 5.1 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.55 (t, J = 8.1 Hz, 1H), 7.42 (t, J = 8.1 Hz, 2H), 7.26 (m, 1H), 7.09 (dd, J = 8.1, 2.5 Hz, 1H), 2.50 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 196.5, 196.1, 165.5 (d, JC-F = 256.1 Hz), 144.2 (d, JC-F = 7.1 Hz), 136.5, 133.3 (d, JC-F = 2.9 Hz), 133.2, 132.0 (d, JCF = 8.7 Hz), 129.2, 128.6, 116.3 (d, JC-F = 21.6 Hz), 115.7 (d, JC-F = 23.1 Hz), 27.1; IR (KBr) υ 2852, 1738, 1681, 1599, 1580, 1451, 1409, 1363, 1264, 1212, 854, 749 cm-1; HRMS (EI) m/z calcd for C15H11FO2 [M]+ 242.0743; found 242.0741. 1-(2-Benzoyl-4-nitrophenyl)ethanone (4g): 1H NMR (700 MHz, CDCl3) δ 8.41 (dd, J = 8.4, 2.3 Hz, 1H), 8.24 (d, J = 2.2 Hz, 1H), 7.98 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 8.2 Hz, 2H), 2.56 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.7, 194.8, 149.0, 143.1, 141.9, 135.9, 133.8, 129.8, 129.5, 128.8, 124.8, 123.4, 28.1; IR (KBr) υ 2853, 1682, 1599, 1450, 1410, 1360, 1314, 1265, 1160, 1074, 964, 886 cm-1; HRMS (EI) m/z calcd for C15H11NO4 [M]+ 269.0688; found 269.0690. 1-(2-Benzoyl-5-methylphenyl)ethanone (4h): 1H NMR (700 MHz, CDCl3) δ 7.74 (d, J = 8.3 Hz, 2H), 7.63 (s, 1H), 7.52 (t, J = 8.1 Hz, 1H), 7.42–7.39 (m, 3H), 7.31 (d, J = 7.7 Hz, 1H), 2.49 (s, 6H); 13C NMR (175 MHz, CDCl3) δ 199.2, 197.8, 140.2, 138.4, 137.8, 137.4, 132.8, 132.5, 129.7, 129.3, 128.6, 128.4, 127.7, 21.4; IR (KBr) υ 2922, 1735, 1681, 1600, 1451, 1359, 1277, 1200, 1055, 1015, 934, 832, 708 cm-1; HRMS (EI) m/z calcd for C16H14O2 [M]+ 238.0994; found 238.1006. 1-(3-Benzoylnaphthalen-2-yl)ethanone (4i): 1H NMR (700 MHz, CDCl3) δ 8.39 (s, 1H), 8.01 (d, J = 7.7 Hz, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.86 (s, 1H), 7.80 (d, J = 8.3 Hz, 2H), 7.68–7.64 (m, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.42 (d, J = 8.2 Hz, 2H), 2.63 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.2, 196.4, 136.6, 136.1, 6 | Journal Name, [year], [vol], 00–00
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134.6, 133.0, 131.8, 131.6, 129.9, 128.4, 128.3, 128.1, 127.9, 127.6, 127.4, 127.1, 26.2; IR (KBr) υ 2923, 1738, 1677, 1597, 1459, 1359, 1313, 1277, 1219, 1198, 1123, 1023, 958, 899, 874, 754 cm-1; HRMS (EI) m/z calcd for C19H14O2 [M]+ 274.0994; found 274.0992. 1-(2-Benzoyl-5-fluorophenyl)ethanone (4ja): 1H NMR (700 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.50 (dd, J = 8.8, 2.5 Hz, 1H), 7.44–7.42 (m, 3H), 7.30 (t, J = 8.0 Hz, 1H), 2.49 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 197.8, 196.5, 163.0 (d, JC-F = 251.6 Hz), 140.7 (d, JC-F = 6.2 Hz), 137.0, 136.3 (d, JC-F = 3.1 Hz), 133.2, 130.7 (d, JC-F = 8.0 Hz), 129.4, 128.6, 118.6 (d, JC-F = 21.4 Hz), 116.1 (d, JC-F = 22.6 Hz), 27.8; IR (KBr) υ 1690, 1671, 1600, 1581, 1487, 1406, 1360, 1273, 1192, 1147, 1073, 964, 875, 799, 750 cm-1; HRMS (EI) m/z calcd for C15H11FO2 [M]+ 242.0743; found 242.0748.
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1-(2-Benzoyl-3-fluorophenyl)ethanone (4jb): 1H NMR (700 MHz, CDCl3) δ 7.78 (d, J = 8.0 Hz, 2H), 7.75 (d, J = 7.7 Hz, 1H), 7.58–7.54 (m, 2H), 7.43 (t, J = 7.7 Hz, 2H), 7.37 (t, J = 7.5 Hz, 1H), 2.54 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 196.7 (d, JC-F = 2.1 Hz), 193.5, 160.3 (d, JC-F = 247.1 Hz), 138.4 (d, JC-F = 3.1 Hz), 137.1, 133.4, 130.8 (d, JC-F = 8.0 Hz), 128.8 (d, JC-F = 19.8 Hz), 128.7, 128.6, 125.6 (d, JC-F = 2.5 Hz), 120.5 (d, JC-F = 22.6 Hz), 27.3; IR (KBr) υ 1739, 1678, 1601, 1577, 1452, 1362, 1314, 1270, 932, 889, 799, 758 cm-1; HRMS (EI) m/z calcd for C15H11FO2 [M]+ 242.0743; found 242.0748. 1-(2-Benzoyl-6-fluorophenyl)ethanone (4k): 1H NMR (700 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.57 (t, J = 7.3 Hz, 1H), 7.53–7.50 (m, 1H), 7.45 (t, J = 7.8 Hz, 2H), 7.28 (t, J = 9.1 Hz, 1H), 7.23 (d, J = 7.5 Hz, 1H), 2.60 (s, 3H); 13C NMR (175 MHz, CDCl3) δ 198.1, 195.9, 160.5 (d, JC-F = 250.0 Hz), 141.7, 136.7, 133.3, 132.1 (d, JC-F = 8.5 Hz), 129.7, 128.6 (d, JC-F = 16.7 Hz), 128.5, 124.9 (d, JC-F = 3.3 Hz), 118.4 (d, JC-F = 23.3 Hz), 31.8 (d, JC-F = 5.4 Hz); IR (KBr) υ 2970, 1738, 1713, 1670, 1451, 1362, 1280, 1055, 1013, 710 cm-1; HRMS (EI) m/z calcd for C15H11FO2 [M]+ 242.0743; found 242.0744. 5-Benzoylchroman-4-one (4l): 1H NMR (700 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.56–7.51 (m, 2H), 7.41 (t, J = 8.1 Hz, 2H), 7.11 (d, J = 8.4 Hz, 1H), 6.90 (d, J = 7.2 Hz, 1H), 4.56 (t, J = 6.3 Hz, 2H), 2.75 (t, J = 6.3 Hz, 2H); 13C NMR (175 MHz, CDCl3) δ 197.3, 190.5, 162.1, 141.8, 136.9, 135.6, 133.0, 129.1, 128.4, 120.2, 119.5, 119.1, 67.0, 37.6; IR (KBr) υ 2833, 1681, 1454, 1114, 1032, 713 cm-1; HRMS (EI) m/z calcd for C16H12O3 [M]+ 252.0786; found 252.0788. 8-Benzoyl-6-methoxy-3,4-dihydronaphthalen-1(2H)-one (4m): 1 H NMR (700 MHz, CDCl3) δ 7.72 (d, J = 8.2 Hz, 2H), 7.48 (t, J = 7.3 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H), 6.80 (s, 1H), 6.67 (s, 1H), 2.97 (t, J = 6.0 Hz, 2H), 2.50 (t, J = 6.7 Hz, 2H), 2.11–2.08 (m, 2H); 13C NMR (175 MHz, CDCl3) δ 197.8, 195.9, 163.0, 147.9, 144.5, 137.1, 132.7, 128.9, 128.4, 124.7, 113.9, 111.9, 55.7, 38.7, 30.4, 23.0; IR (KBr) υ 2938, 1672, 1591, 1454, 1354, 1320, 1277, 1149, 1055, 1007, 719 cm-1; HRMS (EI) m/z calcd for C18H16O3 [M]+ 280.1099; found 280.1100.
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Organic & Biomolecular Chemistry Accepted Manuscript
128.4, 114.4, 113.4, 55.8, 26.6; IR (KBr) υ 1679, 1597, 1566, 1451, 1417, 1360, 1319, 1272, 1233, 1122, 1071, 1026, 955, 841, 749 cm-1; HRMS (EI) m/z calcd for C16H14O3 [M]+ 254.0943; found 254.0944.
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1,2-Phenylenebis(phenylmethanone (4n): 1H NMR (700 MHz, CDCl3) δ 7.70 (d, J = 8.2 Hz, 4H), 7.62–7.61 (m, 4H), 7.51 (t, J = 7.3 Hz, 2H), 7.37 (t, J = 7.7 Hz, 4H); 13C NMR (175 MHz, CDCl3) δ 196.6, 140.0, 137.2, 133.0, 130.4, 129.9, 129.7, 128.4; IR (KBr) υ 2832, 1719, 1657, 1525, 1449, 1397, 1318, 1229, 1105, 1027, 938, 805, 764 cm-1; HRMS (EI) m/z calcd for C20H14O2 [M]+ 286.0994; found 286.0989.
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School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Fax: 82 31 292 8800; Tel: 82 31 290 7788; E-mail: [email protected] b Department of Chemistry, Sookmyung Women’s University, Seoul 140742, Republic of Korea. Fax: 82 2 2077 7321; Tel: 82 2 2077 7549; Email: [email protected] † Electronic Supplementary Information (ESI) available: 1H and 13C NMR copies of all products. See DOI: 10.1039/b000000x/ 1 (a) H. Surburg and J. Panten, Common Fragrance and Flavor Materials, 5th ed.; Wiley-VCH: Weinheim, Germany, 2006; (b) Y. Deng, Y.-W. Chin, H. Chai, W. J. Keller and A. D. Kinghorn, J. Nat. Prod., 2007, 70, 2049; (c) K. R. Romines, G. A. Freeman, L. T. Schaller, J. R. Cowan, S. S. Gonzales, J. H. Tidwell, C. W. Andrews, D. K. Stammers, R. J. Hazen, R. G. Ferris, S. A. Short, J. H. Chan and L. R. Boone, J. Med. Chem., 2006, 49, 727; (d) P. J. Masson, D. Coup, J. Millet and N. L. Brown, J. Bio. Chem., 1994, 270, 2662. 2 A. Kotali and P. A. Harris, Org. Prep. Proced. Int., 2003, 35, 583. 3 (a) F. Weygand, H. Weber, E. Maekawa and G. Eberhardt, Chem. Ber., 1956, 89, 1994; (b) M. Roth, Anal. Chem., 1971, 43, 880; (c) L. A. Sternson, J. F. Stobaugh and A. J. Repta, Anal. Biochem., 1985, 144, 233; (d) S. C. Baele, J. C. Savage, D. Wiesler, S. M. Wiedstock and M. Novotny, Anal. Chem., 1988, 60, 1765. 4 H. Ebrahim and K. Dakshinamurti, Anal. Biochem., 1986, 154, 282. 5 (a) A. Kotali and P. G. Tsoungas, Tetrahedron Lett., 1987, 28, 4321; (b) A. Kotali, U. Glaveri, E. Pavlidou and P. G. Tsoungas, Synthesis, 1990, 12, 1172; (c) A. R. Katrizky and A. Kotali, Tetrahedron Lett., 1990, 31, 6781. 6 (a) R. M. Moriarty, B. A. Berglund and M. S. C. Rao, Synthesis, 1993, 318; (b) H. Xian, Z. Qing and Z. Jizheng, Synth. Commun., 2001, 31, 2413; (c) S. Kumar and D. Kumar, Synth. Commun., 2008, 38, 3683. 7 For selected reviews on C–H bond activation, see: (a) L. Ackermann, Chem. Rev., 2011, 111, 1315; (b) S. H. Cho, J. Y. Kim, J. Kwak and S. Chang, Chem. Soc. Rev., 2011, 40, 5068; (c) J. Wencel-Delord, T. Dröge, F. Kiu and F. Glorius, Chem. Soc. Rev., 2011, 40, 4740; (d) O. Baudoin, Chem. Soc. Rev., 2011, 40, 4902; (e) J. L. Bras and J. Muzart, Chem. Rev., 2011, 111, 1170. 8 For selected examples on sp2 C–H acylation using aldehydes, see: (a) X. Jia, S. Zhang, W. Wang, F. Luo and J. Cheng, Org. Lett., 2009, 11, 3120; (b) J. Park, E. Park, A. Kim, Y. Lee, K.-W. Chi, J. H. Kwak, Y. H. Jung and I. S. Kim, Org. Lett., 2011, 13, 4390; (c) S. Sharma, E. Park, J. Park and I. S. Kim, Org. Lett., 2012, 14, 906; (d) S. Sharma, J. Park, E. Park, A. Kim, M. Kim, J. H. Kwak, Y. H. Jung and I. S. Kim, Adv. Synth. Catal., 2013, 355, 332; (e) C.-W. Chan, Z. Zhou, A. S. C. Chan and W.-Y. Yu, Org. Lett., 2010, 12, 3926; (f) Y. Yang, B. Zhou and Y. Li, Adv. Synth. Catal., 2012, 354, 2916; For selected examples on sp2 C–H acylation using alcohols, see: (g) F. Xiao, Q. Shuai, F. Zhao, O. Baslé, G. Deng and C.-J. Li, Org. Lett., 2011, 13, 1614; (h) J. Park, A. Kim, S. Sharma, M. Kim, E. Park, Y. Jeon, Y. Lee, J. H. Kwak, Y. H. Jung and I. S. Kim, Org. Biomol. Chem., 2013, 11, 2766; (i) M. Kim, S. Sharma, J. Park, M. Kim, Y. Choi, Y. Jeon, J. H. Kwak and I. S. Kim, Tetrahedron, 2013, 69, 6552.. 9 For selected examples on sp2 C–H acylation using α-oxocarboxylic acids, see: (a) P. Fang, M. Li and H. Ge, J. Am. Chem. Soc., 2010, 132, 11898; (b) M. Li and H. Ge, Org. Lett., 2010, 12, 3464; (c) H. Wang, L.-N. Guo and X.-H. Duan, Org. Lett., 2012, 14, 4358; (d) M. Kim, J. Park, S. Sharma, A. Kim, E. Park, J. H. Kwak, Y. H. Jung and I. S. Kim, Chem. Commun., 2013, 49, 925; (e) J. Park, M. Kim, S. Sharma, E. Park, A. Kim, S. H. Lee, J. H. Kwak, Y. H. Jung and I. S.
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Journal Name, [year], [vol], 00–00 | 7
Organic & Biomolecular Chemistry Accepted Manuscript
DOI: 10.1039/C3OB41644E
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