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Metal free catalytic hydroboration of multiple bonds in methanol using N-heterocyclic carbenes under open atmosphere† Kun Wen,a Jinbo Chen,a Feng Gao,a Pinaki S. Bhadury,a Erkang Fanb and Zhihua Sun*a
Received 21st July 2013, Accepted 24th July 2013
An easy to operate method of catalytic hydroboration of unsaturated compounds has been developed
DOI: 10.1039/c3ob41499j
pounds, and alkynes were successfully executed with bis( pinacolato)diboron and N-heterocyclic carbenes in methanol without requiring a transition metal or inert atmosphere.
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with wide substrate scope. Reactions of various aldimines, ketimines, α,β-unsaturated carbonyl com-
Introduction
Results and discussion
Stable N-heterocyclic carbenes (NHC) have recently been employed in many typical organic transformations as potent alternatives to tertiary phosphines in metal–ligand catalysis.1,2 Largely due to their electron richness, NHCs exhibit a wide range of reactivity in the field of organocatalysis. In this context, the activation of diboron for direct hydroboration of a carbonyl or related functional groups (CvO, CvN, or their α,β-unsaturated derivatives) or alkenes and alkynes by NHCs has attracted significant attention in recent years.3–42 We recently prepared a series of N-aryl substituted NHCs based on a benzimidazole core43 for carrying out the catalytic hydroboration of N-sulfinyl aldimines and ketimines in a one-pot procedure.18 The reaction required an inert atmosphere and a Cu(I) catalyst to link with the appropriate NHC ligand precursor. In addition, the reaction was conducted in the aprotic solvent toluene and the required proton for hydroboration was probably supplied during aqueous work up. In order to develop an easy to operate NHC-catalyzed hydroboration technique under open atmosphere without requiring the use of a metal and to further widen the substrate scope, herein we conducted regioselective hydroboration of a series of unsaturated substrates with bis( pinacolato)diboron in protic solvents such as methanol which could provide the necessary proton for the addition.
First, we studied non-catalytic base promoted hydroboration of N-tert-butanesulfinyl tert-butylaldimine 1a to form 3a with bis( pinacolato)diboron (2, B2pin2). The reaction was conducted in d4-MeOH at room temperature and the progress was monitored against an internal standard, 1,3,5-trimethoxybenzene, as described by Ellman et al.9 A wide range of bases were tested and it was found that Cs2CO3 or DBU afforded the product 3a in up to 12% yield (see Table S1 in ESI†). Some bases, such as hydroxides, can cause rapid hydrolysis of B2pin2, without generating the product. It is interesting to note that both inorganic and organic bases could lead to the formation of the desired product suggesting that activation of B2pin2 was caused by base and not by any particular metal ion. Further increase of the amount of the base or temperature did not cause any significant improvement in the yield. So, we next turned our attention to investigating the same reaction under catalytic conditions using 10% triphenylphosphine or selected NHC precursors ( pre-NHC 4–8, Table 1) as potential catalysts. The reactions were carried out on a 2 mmol scale in MeOH at room temperature for 24 h. While practically no product was generated with PPh3, various pre-NHCs (entries 2–9) led to the formation of 3a with yields ranging from 15–88%. The best result was achieved with DBU as the base and NHC precursor 8 (entry 7). The same combination also gave optimum result in our previous report in toluene.18 As stated before, to ascertain the role of protic solvents in the reaction, we further compared the formation of 3a in different solvents under similar conditions. Compared to an 88% yield in MeOH (Table 1), the isolated yield of 3a in EtOH, CF2HCH2OH and CF3CH2OH reached 65%, 72% and 68% respectively. As expected, in the absence of a proton source the desired product was not formed at all when the reactions were
a College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, China. E-mail: [email protected]; Fax: +86-21-67791432; Tel: +86-21-67791432 b Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA † Electronic supplementary information (ESI) available: A table listing screening results with various base and spectra (NMR and MS) of compounds. See DOI: 10.1039/c3ob41499j
6350 | Org. Biomol. Chem., 2013, 11, 6350–6356
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Table 1
Paper Table 2 Synthesis of α-aminoboronates from aldimines and ketimines under optimal conditionsa
Activation of B2pin2 with catalystsa
Entry
Base
Catalyst
Isolated yield (%)
1 2 3 4 5 6 7 8 9
Cs2CO3 NaOMe Cs2CO3 DBU DBU DBU DBU TEA Cs2CO3
PPh3 4 5 5 6 7 8 8 8
Trace 15 22 18 20 45 88 68 72
Entry
R1
R2
Product
Yield (%)
dr
1 2 3 4 5 6 7 8
CH3 Cyclopentyl Phthalimido-(CH2)4 4-Cl-C6H4 4-MeO-C6H4 Et Ph Ph-(CH2)2
H H H H H CH3 CH3 Ph
3b 3c 3d 3e 3f 3g 3h 3i
85 90 85 83 82 79 68 65
>99 : 1 >99 : 1 99 : 1 >99 : 1 99 : 1 73 : 27 69 : 31 71 : 29
a
Reaction conditions: ligand precursor 8 (81 mg, 0.2 mmol), DBU (30 mg, 0.2 mmol), reactant (2.0 mmol) and bis(pinacolato)diboron (559 mg, 2.2 mmol), room temperature for 24 h in 20 mL methanol.
a Reaction conditions: ligand precursor (0.2 mmol), Base (0.2 mmol), N-t-butylsulfinyl trimethylacetaldimine (378 mg, 2.0 mmol) and bis(pinacolato)diboron (559 mg, 2.2 mmol), room temperature for 24 h in 20 mL methanol.
Fig. 1 11B NMR of B2pin2 (2) with base and/or pre-NHC in d4-MeOH (each at 0.2 M). (A) 2 alone; (B) 2 and DBU; (C) 2 and 8; and (D) 2, 8, and DBU.
performed in the aprotic solvents benzene, toluene, CH3CN, THF, 1,4-dioxane, DMF and DMSO. The reaction also failed in water or aqueous alcoholic solvents (H2O, or 2 : 1 MeOH–H2O) which may be attributed to rapid hydrolysis of diboron 2 in a homogeneous aqueous solution. Having established the proper conditions for addition, the hydroboration reaction was further extended to different aldimines and ketimines for the preparation of α-aminoboronic esters in MeOH. The results are depicted in Table 2. For aliphatic or aromatic aldimines (entries 1–5), the yields were all above 80% with a dr ratio of 99 : 1 or better. For ketimines (entries 6–8), the yields were slightly lower (above 65%) with a dr ratio around 70 : 30. These results are comparable to or better than those obtained using our one-pot protocol in toluene. Regarding the mechanism of NHC-mediated hydroboration of multiple bonds in methanol, activation of diboron through the formation of an NHC adduct12,15 or a MeO− adduct27,35 is possible. In either case broad peaks in the 11B NMR spectrum may be observed with very similar chemical shifts at 0–10 ppm representing a polarized sp3 B species. Indeed, in our catalytic system in MeOH, formation of a new sp3 B species corresponding to the activation of 2 was observed when both DBU and 8 were present (Fig. 1, broad peak at 3 ppm for spectrum D). The sharp peak at 8 ppm (Fig. 1B and D) caused by base
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treatment was attributed to [Bpin2]− arising from decomposition of 2.15 ESI-TOF MS analysis of a methanolic solution that contained 2, 8, and DBU detected a molecular ion of 657.3675 with an isotope pattern consistent with molecular formula of C40H47B2N2O5 (exact mass 657.3666). This suggests that an adduct consisting of one molecule each of 8, 2, and MeOH was formed in solution. Therefore, the NMR and MS data are consistent with the formation of a MeOH associated NHC-adduct12,15 to diboron 2 or an NHC-adduct with one MeOH displacing one O–B bond of pinacolatodiboron.14 However, based on spectral data alone, one cannot completely rule out the formation of a MeO− adduct to 2 that is specially associated with a pre-NHC. If an NHC-adduct of 2 is responsible for catalysis, one may expect varying catalytic efficiencies of pre NHC 4–8 (Table 1) depending on their acidities. It is known that N-aryl substitution or phenyl ring fusion to the central imidazole ring can lower the acidity of the proton linked to the carbene center.44–46 1H NMR spectra of 4–8 in d6-DMSO are also consistent with this assumption as an increase in chemical shift value is observed with increase in acidity of the proton linked to the carbene center (9.5 ppm for 4, 9.7 ppm for 5, 9.9 ppm for 6, 10.6 ppm for 7, and 10.8 ppm for 8). Therefore, pre-NHC
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Table 3
Organic & Biomolecular Chemistry Catalytic hydroboration of α,β-unsaturated substrates
Table 4
Entry
R1
R2
R3
X
Product
Yield (%)
1 2 3 4 5
H H H CH3 H
H Ph Ph CH3 H
4-Me-C6H4 Ph MeO H 4-Me-C6H4
O O O NS(O)Bu NS(O)Bu
11a 11b 11c 11d 11e
86 85 87a 91 90
a
Reaction performed at 70 °C.
Entry
R1
R2
Product
Yield (%)
α:β
1 2 3 4 5 6 7 8 9
Ph 4-F-C6H4 n-Butyl HOCH2HO(CH2)2CyclopropylBocNH-CH2Me3SiPh
H H H H H H H H Et-
13a 13b 13c 13d 13e 13f 13g 13h 13i
89 88 76 85 91 86 72 75 84a
99 : 1; 19 F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereomer δ = −68.58, minor diastereomer δ = −68.89; 1 H NMR (400 MHz, DMSO-d6, δ): 7.36 (m, 4H), 5.56 (d, J = 5.6 Hz, 1H), 4.08 (d, J = 5.6 Hz, 1H), 1.12 (m, 21H); 13C NMR (100 MHz, DMSO-d6, δ): 104.7, 131.3, 129.4, 128.5, 84.3, 56.2, 46.8, 24.9, 24.5, 23.1; MS (ESI-TOF) m/z: 372.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C17H28BNSClO3 [M + H]+ 372.1566, found 372.1574. Pinacol (R)-1-N-sulfinyl-4-methoxyphenyl-1-boronate (3f ). Colorless oil; 602 mg (yield 82%); dr = 99 : 1; 19F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereomer δ = −68.80, minor diastereomer δ = −68.53; 1H NMR (400 MHz, DMSO-d6, δ): 7.23 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 5.27 (d, J = 5.2 Hz, 1H), 3.99 (d, J = 5.2 Hz, 1H), 3.72 (s, 3H), 1.13 (s, 15H), 1.11 (s, 6H); 13C NMR (100 MHz, DMSO-d6, δ): 158.4, 133.1, 128.9, 114.1, 84.0, 56.1, 55.5, 46.8, 24.9, 24.5, 23.1; MS (ESI-TOF) m/z: 368.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C18H31BNSO4 [M + H]+ 368.2061, found 368.2054. Pinacol (R)-1-N-sulfinyl-1-methyl-ethyl-1-boronate (3g). Colorless oil; 479 mg (yield 79%); dr = 73 : 27; 19F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereomer δ = −68.64, minor diastereomer δ = −68.88; 1H NMR (400 MHz, DMSO-d6, δ): 4.34 (s, 1H), 1.63 (m, 1H), 1.51 (m, 1H), 1.21 (d, J = 3.2 Hz, 12H), 1.13 (m, 12H), 0.84 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, DMSO-d6, δ): 84.1, 55.4, 32.7, 25.1, 24.9, 24.0, 23.0, 22.2; MS (ESI-TOF) m/z: 304.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C14H31BNSO3 [M + H]+ 304.2112, found 304.2105. Pinacol (R)-1-N-sulfinyl-phenyl-methyl-1-boronate (3h). Colorless oil; 477 mg (yield 68%); dr = 69 : 31; 19F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereomer δ = −68.80, minor diastereomer δ = −69.16; 1H NMR (400 MHz, DMSO-d6, δ): 7.40 (m, 2H), 7.31 (m, 2H), 7.18 (m, 1H), 5.18 (s, 0.34H), 5.15 (s, 0.51H), 1.64 (s, 1.22H), 1.58 (s, 1.78H), 1.20 (s, 9H), 1.16 (s, 12H), 1.13 (s, 6H); 13C NMR (100 MHz, DMSO-d6, δ): 146.2, 146.1, 128.3, 128.2, 127.2, 126.3, 126.2, 84.4, 84.2, 56.7, 55.8, 25.0, 24.9, 24.9, 24.6, 24.4, 23.4, 23.2; MS (ESI-TOF) m/z: 352.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C18H31BNSO3 [M + H]+ 352.2112, found 352.2119. Pinacol (R)-1-N-sulfinyl-(2-phenylethyl)-phenyl-1-boronate (3i). Colorless oil; 750 mg (yield 85%); dr = 71 : 29; 19F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major
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Paper diastereomer δ = −69.08, minor diastereomer δ = −69.01; 1H NMR (400 MHz, DMSO-d6, δ): 7.42 (m, 4H), 7.23 (m, 6H), 5.25 (s, 0.63H), 5.05 (s, 0.25H), 2.73 (m, 1H), 2.35 (m, 2H), 2.17 (m, 1H), 1.25 (m, 12H), 1.07 (m, 9H); 13C NMR (100 MHz, DMSOd6, δ): 143.3, 143.1, 128.8, 128.8, 128.7, 128.6, 128.5, 128.3, 128.0, 127.7, 127.6, 127.5, 126.6, 126.5, 126.3, 126.2, 126.0, 84.7, 84.2, 57.0, 56.1, 55.9, 48.9, 31.8, 29.5, 29.2, 25.0, 24.8, 24.6, 24.4, 23.6, 23.3, 23.2, 22.5; MS (ESI-TOF) m/z: 442.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C25H37BNSO3 [M + H]+ 442.2582, Found 442.2575. 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(4-methylphenyl)-butane-2-one (11a). White solid; 471 mg (yield 86%); mp 47.8–49.0 °C; 1H NMR (400 MHz, DMSO-d6, δ): 7.84 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 3.07 (m, 2H), 2.37 (s, 3H), 1.16 (s, 12H), 0.87 (t, J = 6.8 Hz, 2H); 13C NMR (100 MHz, DMSO-d6, δ): 200.2, 143.7, 134.5, 129.6, 128.3, 83.0, 33.6, 25.3, 25.0, 21.6, 5.4; MS (ESI-TOF) m/z: 275.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C16H23BO3Na [M + Na]+ 297.1632, Found 297.1630. 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-phenyl-1-phenylbutane-2-one (11b). White solid; 571 mg (yield 85%); mp 78.6–79.7 °C; 1H NMR (400 MHz, CDCl3, δ): 8.00 (d, J = 7.2 Hz, 2H), 7.57 (m, 1H), 7.46 (m, 2H), 7.33 (m, 4H), 7.22 (m, 1H), 3.59 (dd, J1 = 10.8 Hz, J2 = 18.0 Hz, 1H), 3.45 (dd, J1 = 5.2 Hz, J2 = 18.4 Hz, 1H), 2.83 (dd, J1 = 5.2 Hz, J2 = 10.8 Hz, 1H), 1.28 (s, 6H), 1.20 (s, 6H); 13C NMR (100 MHz, CDCl3, δ): 199.7, 142.0, 136.8, 132.9, 128.5, 128.4, 128.1, 125.6, 83.4, 43.3, 24.6, 24.5; MS (ESI-TOF) m/z: 337.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C21H25BO3Na [M + Na]+ 359.1789, Found 359.1778. Methyl-3-(4,4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-phenyl propionate (11c). White solid; 505 mg (yield 87%); mp 67.6–68.5 °C; 1H NMR (400 MHz, CDCl3, δ): 7.27 (m, 4H), 7.17 (m, 1H), 3.67 (s, 3H), 2.92 (dd, J1 = 15.6 Hz, J2 = 10.0 Hz, 1H), 2.76 (dd, J1 = 10.0 Hz, J2 = 6.0 Hz, 1H), 2.69 (dd, J1 = 15.6 Hz, J2 = 6.0 Hz, 1H), 1.22 (d, J = 18.0 Hz, 12H); 13C NMR (100 MHz, CDCl3, δ): 173.8, 141.3, 128.5, 128.2, 125.7, 83.6, 51.6, 37.1, 24.6, 24.5; MS (ESI-TOF) m/z: 291.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C16H24BO4 [M + H]+ 291.1762, Found 291.1768. (R)-1-N-Sulfinyl-3-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-butene (11d). Colorless oil; 573 mg (yield 91%); 1H NMR (400 MHz, CDCl3, δ): 5.98 (dd, J1 = 10.4 Hz, J2 = 14.0 Hz, 1H), 5.14 (d, J = 14.0 Hz, 1H), 5.01 (d, J = 10.0 Hz, 1H), 1.24 (s, 9H), 1.23 (s, 12H), 1.05 (s, 6H); 13C NMR (100 MHz, CDCl3, δ): 125.3, 120.5, 83.2, 56.2, 24.9, 24.6, 24.5, 24.4, 22.5; MS (ESI-TOF) m/z: 316.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C15H30BNSO3Na [M + Na]+ 338.1932, Found 338.1913. (R)-1-N-Sulfinyl-1-(4-methylphenyl)-3-(4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl)-1-propene (11e). Colorless oil; 643 mg (yield 90%); 1H NMR (400 MHz, CDCl3, δ): 7.35 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 5.44 (t, J = 8.0 Hz, 1H), 4.86 (s, 1H), 2.37 (s, 3H), 1.71 (dd, J1 = 4.8 Hz, J2 = 8.0 Hz, 2H), 1.27 (s, 9H), 1.24 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 138.0, 137.9, 133.3, 129.5, 129.0, 110.4, 83.3, 55.9, 24.8, 24.8, 22.7, 21.3; MS (ESI-TOF) m/z: 358.3 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C21H32BNSO3Na [M + Na]+ 400.2088, Found 400.2061.
6354 | Org. Biomol. Chem., 2013, 11, 6350–6356
Organic & Biomolecular Chemistry 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-phenyl-ethene (13a). White Solid; 409 mg (yield 89%); mp 31.4–32.4 °C; 1 H NMR (400 MHz, CDCl3, δ): 7.52 (m, 2H), 7.43 (d, J = 18.4 Hz, 1H), 7.34 (m, 3H), 6.21 (d, J = 18.4 Hz, 1H), 1.34 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 149.5, 137.5, 128.9, 128.6, 127.1, 83.4, 24.8; MS (ESI-TOF) m/z: 231.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C14H20BO2 [M + H]+ 231.1551, Found 231.1550. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(4-fluorophenyl)-ethene (13b). White solid; 436 mg (yield 88%); mp 63.9–65.4 °C; 1H NMR (400 MHz, CDCl3, δ): 7.48 (m, 2H), 7.38 (d, J = 18.4 Hz, 1H), 7.05 (t, J = 8.8 Hz, 2H), 6.10 (d, J = 18.4 Hz, 1H), 1.34 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 163.2, 148.2, 133.7, 128.7, 128.7, 115.7, 115.4, 83.4, 24.8; 19F NMR (376 MHz, CDCl3, δ): −112.4; MS (ESI-TOF) m/z: 249.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C14H19BFO2 [M + H]+ 249.1457, Found 249.1455. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-hexene (13c). Colorless oil; 319 mg (yield 76%); 1H NMR (400 MHz, DMSOd6, δ): 6.05 (dt, J1 = 17.6 Hz, J2 = 6.4 Hz, 1H), 5.30 (m, 1H), 2.11 (m, 2H), 1.35 (m, 2H), 1.25 (m, 2H), 1.18 (s, 12H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, DMSO-d6, δ): 154.7, 118.5, 83.1, 35.3, 30.3, 25.1, 22.2, 14.2; MS (ESI-TOF) m/z: 211.2[M + H]+; HRMS (ESI-TOF) m/z: calcd for C12H24BO2 [M + H]+ 211.1864, Found 211.1869. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-hydroxy1-propene (13d). Colorless oil; 313 mg (yield 85%); 1H NMR (400 MHz, CDCl3, δ): 6.76 (dd, J1 = 18.4 Hz, J2 = 4 Hz, 1H), 5.73 (d, J = 18.4 Hz, 1H), 4.26 (d, J = 2.4 Hz, 2H), 1.62 (s, 1H), 1.30 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 151.7, 83.3, 64.6, 24.8; MS (ESI-TOF) m/z: 185.1 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C9H18BO3 [M + H]+ 185.1344, Found 185.1348. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-hydroxy1-butene (13e). Colorless oil; 360 mg (yield 91%); 1H NMR (400 MHz, CDCl3, δ): 6.60 (dt, J1 = 18 Hz, J2 = 6.4 Hz, 1H), 5.54 (d, J = 18 Hz, 1H), 3.71 (t, J = 6.4 Hz, 2H), 2.42 (m, 2H), 1.88 (s, 1H), 1.26 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 150.1, 121.9, 83.2, 61.2, 39.1, 24.8; MS (ESI-TOF) m/z: 199.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C10H20BO3 [M + H]+ 199.1505, Found 199.1500. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-cyclopyl-ethene (13f ). Colorless oil; 334 mg (yield 86%); 1H NMR (400 MHz, CDCl3, δ): 6.09 (dd, J1 = 18 Hz, J2 = 4 Hz, 1H), 5.50 (d, J1 = 18 Hz, 1H), 1.53 (m, 1H), 1.26 (s, 12H), 0.81 (m, 2H), 0.54 (m, 2H); 13C NMR (100 MHz, CDCl3, δ): 158.5, 115.3, 82.9, 24.7, 17.0, 7.9; MS (ESI-TOF) m/z: 195.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C11H20BO2 [M + H]+ 195.1551, Found 195.1557. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-N-Boc-3-amino1-propene (13g). White solid; 407 mg (yield 72%); mp 61.6–62.8 °C; 1H NMR (400 MHz, CDCl3, δ): 6.59 (dt, J1 = 18 Hz, J2 = 4 Hz, 1H), 5.59 (dt, J1 = 18 Hz, J2 = 6 Hz, 1H), 4.67 (s, 1H), 3.85 (m, 2H), 1.45 (s, 9H), 1.27 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 155.7, 149.4, 118.3, 83.3, 79.4, 44.0, 28.4, 24.8; MS (ESI-TOF) m/z: 284.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C14H27BNO4 [M + H]+ 284.2024, Found 284.2028.
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Organic & Biomolecular Chemistry 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-trimethylsilylethene (13h). Colorless oil; 340 mg (yield 75%); 1H NMR (400 MHz, CDCl3, δ): 7.14 (d, J = 22 Hz, 1H), 6.26 (d, J = 22 Hz, 1H), 1.30 (s, 12H), 0.1 (s, 9H); 13C NMR (100 MHz, CDCl3, δ): 157.9, 83.4, 24.8, 1.9; MS (ESI-TOF) m/z: 227.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C11H24BO2Si [M + H]+ 227.1633, Found 227.1638. 1-Phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-butene (13i). Colorless oil; 433 mg (yield 84%); 1H NMR (400 MHz, CDCl3, δ): 7.36 (m, 4H), 7.28 (m, 2H), 2.46 (q, J = 7.6 Hz, 2H), 1.36 (s, 12H), 1.16 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3, δ): 141.4, 137.9, 129.0, 128.1, 127.1, 83.4, 24.8, 22.7, 14.7; MS (ESI-TOF) m/z: 259.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C16H24BO2Si [M + H]+ 259.1864, Found 259.1868.
Acknowledgements Financial support of this work was provided by Shanghai Saijia Chemicals Ltd., Shanghai Municipal Science and Technology Commission (Project no. 12430501300), and the Innovation Team Building Project of Pharmaceutical Engineering in Shanghai (XKZZ1205).
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PAPER
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Metal free catalytic hydroboration of multiple bonds in methanol using N-heterocyclic carbenes under open atmosphere† Kun Wen,a Jinbo Chen,a Feng Gao,a Pinaki S. Bhadury,a Erkang Fanb and Zhihua Sun*a
Received 21st July 2013, Accepted 24th July 2013
An easy to operate method of catalytic hydroboration of unsaturated compounds has been developed
DOI: 10.1039/c3ob41499j
pounds, and alkynes were successfully executed with bis( pinacolato)diboron and N-heterocyclic carbenes in methanol without requiring a transition metal or inert atmosphere.
www.rsc.org/obc
with wide substrate scope. Reactions of various aldimines, ketimines, α,β-unsaturated carbonyl com-
Introduction
Results and discussion
Stable N-heterocyclic carbenes (NHC) have recently been employed in many typical organic transformations as potent alternatives to tertiary phosphines in metal–ligand catalysis.1,2 Largely due to their electron richness, NHCs exhibit a wide range of reactivity in the field of organocatalysis. In this context, the activation of diboron for direct hydroboration of a carbonyl or related functional groups (CvO, CvN, or their α,β-unsaturated derivatives) or alkenes and alkynes by NHCs has attracted significant attention in recent years.3–42 We recently prepared a series of N-aryl substituted NHCs based on a benzimidazole core43 for carrying out the catalytic hydroboration of N-sulfinyl aldimines and ketimines in a one-pot procedure.18 The reaction required an inert atmosphere and a Cu(I) catalyst to link with the appropriate NHC ligand precursor. In addition, the reaction was conducted in the aprotic solvent toluene and the required proton for hydroboration was probably supplied during aqueous work up. In order to develop an easy to operate NHC-catalyzed hydroboration technique under open atmosphere without requiring the use of a metal and to further widen the substrate scope, herein we conducted regioselective hydroboration of a series of unsaturated substrates with bis( pinacolato)diboron in protic solvents such as methanol which could provide the necessary proton for the addition.
First, we studied non-catalytic base promoted hydroboration of N-tert-butanesulfinyl tert-butylaldimine 1a to form 3a with bis( pinacolato)diboron (2, B2pin2). The reaction was conducted in d4-MeOH at room temperature and the progress was monitored against an internal standard, 1,3,5-trimethoxybenzene, as described by Ellman et al.9 A wide range of bases were tested and it was found that Cs2CO3 or DBU afforded the product 3a in up to 12% yield (see Table S1 in ESI†). Some bases, such as hydroxides, can cause rapid hydrolysis of B2pin2, without generating the product. It is interesting to note that both inorganic and organic bases could lead to the formation of the desired product suggesting that activation of B2pin2 was caused by base and not by any particular metal ion. Further increase of the amount of the base or temperature did not cause any significant improvement in the yield. So, we next turned our attention to investigating the same reaction under catalytic conditions using 10% triphenylphosphine or selected NHC precursors ( pre-NHC 4–8, Table 1) as potential catalysts. The reactions were carried out on a 2 mmol scale in MeOH at room temperature for 24 h. While practically no product was generated with PPh3, various pre-NHCs (entries 2–9) led to the formation of 3a with yields ranging from 15–88%. The best result was achieved with DBU as the base and NHC precursor 8 (entry 7). The same combination also gave optimum result in our previous report in toluene.18 As stated before, to ascertain the role of protic solvents in the reaction, we further compared the formation of 3a in different solvents under similar conditions. Compared to an 88% yield in MeOH (Table 1), the isolated yield of 3a in EtOH, CF2HCH2OH and CF3CH2OH reached 65%, 72% and 68% respectively. As expected, in the absence of a proton source the desired product was not formed at all when the reactions were
a College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, China. E-mail: [email protected]; Fax: +86-21-67791432; Tel: +86-21-67791432 b Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA † Electronic supplementary information (ESI) available: A table listing screening results with various base and spectra (NMR and MS) of compounds. See DOI: 10.1039/c3ob41499j
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Table 1
Paper Table 2 Synthesis of α-aminoboronates from aldimines and ketimines under optimal conditionsa
Activation of B2pin2 with catalystsa
Entry
Base
Catalyst
Isolated yield (%)
1 2 3 4 5 6 7 8 9
Cs2CO3 NaOMe Cs2CO3 DBU DBU DBU DBU TEA Cs2CO3
PPh3 4 5 5 6 7 8 8 8
Trace 15 22 18 20 45 88 68 72
Entry
R1
R2
Product
Yield (%)
dr
1 2 3 4 5 6 7 8
CH3 Cyclopentyl Phthalimido-(CH2)4 4-Cl-C6H4 4-MeO-C6H4 Et Ph Ph-(CH2)2
H H H H H CH3 CH3 Ph
3b 3c 3d 3e 3f 3g 3h 3i
85 90 85 83 82 79 68 65
>99 : 1 >99 : 1 99 : 1 >99 : 1 99 : 1 73 : 27 69 : 31 71 : 29
a
Reaction conditions: ligand precursor 8 (81 mg, 0.2 mmol), DBU (30 mg, 0.2 mmol), reactant (2.0 mmol) and bis(pinacolato)diboron (559 mg, 2.2 mmol), room temperature for 24 h in 20 mL methanol.
a Reaction conditions: ligand precursor (0.2 mmol), Base (0.2 mmol), N-t-butylsulfinyl trimethylacetaldimine (378 mg, 2.0 mmol) and bis(pinacolato)diboron (559 mg, 2.2 mmol), room temperature for 24 h in 20 mL methanol.
Fig. 1 11B NMR of B2pin2 (2) with base and/or pre-NHC in d4-MeOH (each at 0.2 M). (A) 2 alone; (B) 2 and DBU; (C) 2 and 8; and (D) 2, 8, and DBU.
performed in the aprotic solvents benzene, toluene, CH3CN, THF, 1,4-dioxane, DMF and DMSO. The reaction also failed in water or aqueous alcoholic solvents (H2O, or 2 : 1 MeOH–H2O) which may be attributed to rapid hydrolysis of diboron 2 in a homogeneous aqueous solution. Having established the proper conditions for addition, the hydroboration reaction was further extended to different aldimines and ketimines for the preparation of α-aminoboronic esters in MeOH. The results are depicted in Table 2. For aliphatic or aromatic aldimines (entries 1–5), the yields were all above 80% with a dr ratio of 99 : 1 or better. For ketimines (entries 6–8), the yields were slightly lower (above 65%) with a dr ratio around 70 : 30. These results are comparable to or better than those obtained using our one-pot protocol in toluene. Regarding the mechanism of NHC-mediated hydroboration of multiple bonds in methanol, activation of diboron through the formation of an NHC adduct12,15 or a MeO− adduct27,35 is possible. In either case broad peaks in the 11B NMR spectrum may be observed with very similar chemical shifts at 0–10 ppm representing a polarized sp3 B species. Indeed, in our catalytic system in MeOH, formation of a new sp3 B species corresponding to the activation of 2 was observed when both DBU and 8 were present (Fig. 1, broad peak at 3 ppm for spectrum D). The sharp peak at 8 ppm (Fig. 1B and D) caused by base
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treatment was attributed to [Bpin2]− arising from decomposition of 2.15 ESI-TOF MS analysis of a methanolic solution that contained 2, 8, and DBU detected a molecular ion of 657.3675 with an isotope pattern consistent with molecular formula of C40H47B2N2O5 (exact mass 657.3666). This suggests that an adduct consisting of one molecule each of 8, 2, and MeOH was formed in solution. Therefore, the NMR and MS data are consistent with the formation of a MeOH associated NHC-adduct12,15 to diboron 2 or an NHC-adduct with one MeOH displacing one O–B bond of pinacolatodiboron.14 However, based on spectral data alone, one cannot completely rule out the formation of a MeO− adduct to 2 that is specially associated with a pre-NHC. If an NHC-adduct of 2 is responsible for catalysis, one may expect varying catalytic efficiencies of pre NHC 4–8 (Table 1) depending on their acidities. It is known that N-aryl substitution or phenyl ring fusion to the central imidazole ring can lower the acidity of the proton linked to the carbene center.44–46 1H NMR spectra of 4–8 in d6-DMSO are also consistent with this assumption as an increase in chemical shift value is observed with increase in acidity of the proton linked to the carbene center (9.5 ppm for 4, 9.7 ppm for 5, 9.9 ppm for 6, 10.6 ppm for 7, and 10.8 ppm for 8). Therefore, pre-NHC
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Table 3
Organic & Biomolecular Chemistry Catalytic hydroboration of α,β-unsaturated substrates
Table 4
Entry
R1
R2
R3
X
Product
Yield (%)
1 2 3 4 5
H H H CH3 H
H Ph Ph CH3 H
4-Me-C6H4 Ph MeO H 4-Me-C6H4
O O O NS(O)Bu NS(O)Bu
11a 11b 11c 11d 11e
86 85 87a 91 90
a
Reaction performed at 70 °C.
Entry
R1
R2
Product
Yield (%)
α:β
1 2 3 4 5 6 7 8 9
Ph 4-F-C6H4 n-Butyl HOCH2HO(CH2)2CyclopropylBocNH-CH2Me3SiPh
H H H H H H H H Et-
13a 13b 13c 13d 13e 13f 13g 13h 13i
89 88 76 85 91 86 72 75 84a
99 : 1; 19 F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereomer δ = −68.58, minor diastereomer δ = −68.89; 1 H NMR (400 MHz, DMSO-d6, δ): 7.36 (m, 4H), 5.56 (d, J = 5.6 Hz, 1H), 4.08 (d, J = 5.6 Hz, 1H), 1.12 (m, 21H); 13C NMR (100 MHz, DMSO-d6, δ): 104.7, 131.3, 129.4, 128.5, 84.3, 56.2, 46.8, 24.9, 24.5, 23.1; MS (ESI-TOF) m/z: 372.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C17H28BNSClO3 [M + H]+ 372.1566, found 372.1574. Pinacol (R)-1-N-sulfinyl-4-methoxyphenyl-1-boronate (3f ). Colorless oil; 602 mg (yield 82%); dr = 99 : 1; 19F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereomer δ = −68.80, minor diastereomer δ = −68.53; 1H NMR (400 MHz, DMSO-d6, δ): 7.23 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 5.27 (d, J = 5.2 Hz, 1H), 3.99 (d, J = 5.2 Hz, 1H), 3.72 (s, 3H), 1.13 (s, 15H), 1.11 (s, 6H); 13C NMR (100 MHz, DMSO-d6, δ): 158.4, 133.1, 128.9, 114.1, 84.0, 56.1, 55.5, 46.8, 24.9, 24.5, 23.1; MS (ESI-TOF) m/z: 368.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C18H31BNSO4 [M + H]+ 368.2061, found 368.2054. Pinacol (R)-1-N-sulfinyl-1-methyl-ethyl-1-boronate (3g). Colorless oil; 479 mg (yield 79%); dr = 73 : 27; 19F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereomer δ = −68.64, minor diastereomer δ = −68.88; 1H NMR (400 MHz, DMSO-d6, δ): 4.34 (s, 1H), 1.63 (m, 1H), 1.51 (m, 1H), 1.21 (d, J = 3.2 Hz, 12H), 1.13 (m, 12H), 0.84 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, DMSO-d6, δ): 84.1, 55.4, 32.7, 25.1, 24.9, 24.0, 23.0, 22.2; MS (ESI-TOF) m/z: 304.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C14H31BNSO3 [M + H]+ 304.2112, found 304.2105. Pinacol (R)-1-N-sulfinyl-phenyl-methyl-1-boronate (3h). Colorless oil; 477 mg (yield 68%); dr = 69 : 31; 19F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereomer δ = −68.80, minor diastereomer δ = −69.16; 1H NMR (400 MHz, DMSO-d6, δ): 7.40 (m, 2H), 7.31 (m, 2H), 7.18 (m, 1H), 5.18 (s, 0.34H), 5.15 (s, 0.51H), 1.64 (s, 1.22H), 1.58 (s, 1.78H), 1.20 (s, 9H), 1.16 (s, 12H), 1.13 (s, 6H); 13C NMR (100 MHz, DMSO-d6, δ): 146.2, 146.1, 128.3, 128.2, 127.2, 126.3, 126.2, 84.4, 84.2, 56.7, 55.8, 25.0, 24.9, 24.9, 24.6, 24.4, 23.4, 23.2; MS (ESI-TOF) m/z: 352.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C18H31BNSO3 [M + H]+ 352.2112, found 352.2119. Pinacol (R)-1-N-sulfinyl-(2-phenylethyl)-phenyl-1-boronate (3i). Colorless oil; 750 mg (yield 85%); dr = 71 : 29; 19F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major
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Paper diastereomer δ = −69.08, minor diastereomer δ = −69.01; 1H NMR (400 MHz, DMSO-d6, δ): 7.42 (m, 4H), 7.23 (m, 6H), 5.25 (s, 0.63H), 5.05 (s, 0.25H), 2.73 (m, 1H), 2.35 (m, 2H), 2.17 (m, 1H), 1.25 (m, 12H), 1.07 (m, 9H); 13C NMR (100 MHz, DMSOd6, δ): 143.3, 143.1, 128.8, 128.8, 128.7, 128.6, 128.5, 128.3, 128.0, 127.7, 127.6, 127.5, 126.6, 126.5, 126.3, 126.2, 126.0, 84.7, 84.2, 57.0, 56.1, 55.9, 48.9, 31.8, 29.5, 29.2, 25.0, 24.8, 24.6, 24.4, 23.6, 23.3, 23.2, 22.5; MS (ESI-TOF) m/z: 442.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C25H37BNSO3 [M + H]+ 442.2582, Found 442.2575. 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(4-methylphenyl)-butane-2-one (11a). White solid; 471 mg (yield 86%); mp 47.8–49.0 °C; 1H NMR (400 MHz, DMSO-d6, δ): 7.84 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 3.07 (m, 2H), 2.37 (s, 3H), 1.16 (s, 12H), 0.87 (t, J = 6.8 Hz, 2H); 13C NMR (100 MHz, DMSO-d6, δ): 200.2, 143.7, 134.5, 129.6, 128.3, 83.0, 33.6, 25.3, 25.0, 21.6, 5.4; MS (ESI-TOF) m/z: 275.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C16H23BO3Na [M + Na]+ 297.1632, Found 297.1630. 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-phenyl-1-phenylbutane-2-one (11b). White solid; 571 mg (yield 85%); mp 78.6–79.7 °C; 1H NMR (400 MHz, CDCl3, δ): 8.00 (d, J = 7.2 Hz, 2H), 7.57 (m, 1H), 7.46 (m, 2H), 7.33 (m, 4H), 7.22 (m, 1H), 3.59 (dd, J1 = 10.8 Hz, J2 = 18.0 Hz, 1H), 3.45 (dd, J1 = 5.2 Hz, J2 = 18.4 Hz, 1H), 2.83 (dd, J1 = 5.2 Hz, J2 = 10.8 Hz, 1H), 1.28 (s, 6H), 1.20 (s, 6H); 13C NMR (100 MHz, CDCl3, δ): 199.7, 142.0, 136.8, 132.9, 128.5, 128.4, 128.1, 125.6, 83.4, 43.3, 24.6, 24.5; MS (ESI-TOF) m/z: 337.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C21H25BO3Na [M + Na]+ 359.1789, Found 359.1778. Methyl-3-(4,4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-phenyl propionate (11c). White solid; 505 mg (yield 87%); mp 67.6–68.5 °C; 1H NMR (400 MHz, CDCl3, δ): 7.27 (m, 4H), 7.17 (m, 1H), 3.67 (s, 3H), 2.92 (dd, J1 = 15.6 Hz, J2 = 10.0 Hz, 1H), 2.76 (dd, J1 = 10.0 Hz, J2 = 6.0 Hz, 1H), 2.69 (dd, J1 = 15.6 Hz, J2 = 6.0 Hz, 1H), 1.22 (d, J = 18.0 Hz, 12H); 13C NMR (100 MHz, CDCl3, δ): 173.8, 141.3, 128.5, 128.2, 125.7, 83.6, 51.6, 37.1, 24.6, 24.5; MS (ESI-TOF) m/z: 291.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C16H24BO4 [M + H]+ 291.1762, Found 291.1768. (R)-1-N-Sulfinyl-3-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-butene (11d). Colorless oil; 573 mg (yield 91%); 1H NMR (400 MHz, CDCl3, δ): 5.98 (dd, J1 = 10.4 Hz, J2 = 14.0 Hz, 1H), 5.14 (d, J = 14.0 Hz, 1H), 5.01 (d, J = 10.0 Hz, 1H), 1.24 (s, 9H), 1.23 (s, 12H), 1.05 (s, 6H); 13C NMR (100 MHz, CDCl3, δ): 125.3, 120.5, 83.2, 56.2, 24.9, 24.6, 24.5, 24.4, 22.5; MS (ESI-TOF) m/z: 316.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C15H30BNSO3Na [M + Na]+ 338.1932, Found 338.1913. (R)-1-N-Sulfinyl-1-(4-methylphenyl)-3-(4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl)-1-propene (11e). Colorless oil; 643 mg (yield 90%); 1H NMR (400 MHz, CDCl3, δ): 7.35 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H), 5.44 (t, J = 8.0 Hz, 1H), 4.86 (s, 1H), 2.37 (s, 3H), 1.71 (dd, J1 = 4.8 Hz, J2 = 8.0 Hz, 2H), 1.27 (s, 9H), 1.24 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 138.0, 137.9, 133.3, 129.5, 129.0, 110.4, 83.3, 55.9, 24.8, 24.8, 22.7, 21.3; MS (ESI-TOF) m/z: 358.3 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C21H32BNSO3Na [M + Na]+ 400.2088, Found 400.2061.
6354 | Org. Biomol. Chem., 2013, 11, 6350–6356
Organic & Biomolecular Chemistry 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-phenyl-ethene (13a). White Solid; 409 mg (yield 89%); mp 31.4–32.4 °C; 1 H NMR (400 MHz, CDCl3, δ): 7.52 (m, 2H), 7.43 (d, J = 18.4 Hz, 1H), 7.34 (m, 3H), 6.21 (d, J = 18.4 Hz, 1H), 1.34 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 149.5, 137.5, 128.9, 128.6, 127.1, 83.4, 24.8; MS (ESI-TOF) m/z: 231.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C14H20BO2 [M + H]+ 231.1551, Found 231.1550. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(4-fluorophenyl)-ethene (13b). White solid; 436 mg (yield 88%); mp 63.9–65.4 °C; 1H NMR (400 MHz, CDCl3, δ): 7.48 (m, 2H), 7.38 (d, J = 18.4 Hz, 1H), 7.05 (t, J = 8.8 Hz, 2H), 6.10 (d, J = 18.4 Hz, 1H), 1.34 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 163.2, 148.2, 133.7, 128.7, 128.7, 115.7, 115.4, 83.4, 24.8; 19F NMR (376 MHz, CDCl3, δ): −112.4; MS (ESI-TOF) m/z: 249.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C14H19BFO2 [M + H]+ 249.1457, Found 249.1455. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-hexene (13c). Colorless oil; 319 mg (yield 76%); 1H NMR (400 MHz, DMSOd6, δ): 6.05 (dt, J1 = 17.6 Hz, J2 = 6.4 Hz, 1H), 5.30 (m, 1H), 2.11 (m, 2H), 1.35 (m, 2H), 1.25 (m, 2H), 1.18 (s, 12H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, DMSO-d6, δ): 154.7, 118.5, 83.1, 35.3, 30.3, 25.1, 22.2, 14.2; MS (ESI-TOF) m/z: 211.2[M + H]+; HRMS (ESI-TOF) m/z: calcd for C12H24BO2 [M + H]+ 211.1864, Found 211.1869. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-hydroxy1-propene (13d). Colorless oil; 313 mg (yield 85%); 1H NMR (400 MHz, CDCl3, δ): 6.76 (dd, J1 = 18.4 Hz, J2 = 4 Hz, 1H), 5.73 (d, J = 18.4 Hz, 1H), 4.26 (d, J = 2.4 Hz, 2H), 1.62 (s, 1H), 1.30 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 151.7, 83.3, 64.6, 24.8; MS (ESI-TOF) m/z: 185.1 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C9H18BO3 [M + H]+ 185.1344, Found 185.1348. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-hydroxy1-butene (13e). Colorless oil; 360 mg (yield 91%); 1H NMR (400 MHz, CDCl3, δ): 6.60 (dt, J1 = 18 Hz, J2 = 6.4 Hz, 1H), 5.54 (d, J = 18 Hz, 1H), 3.71 (t, J = 6.4 Hz, 2H), 2.42 (m, 2H), 1.88 (s, 1H), 1.26 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 150.1, 121.9, 83.2, 61.2, 39.1, 24.8; MS (ESI-TOF) m/z: 199.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C10H20BO3 [M + H]+ 199.1505, Found 199.1500. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-cyclopyl-ethene (13f ). Colorless oil; 334 mg (yield 86%); 1H NMR (400 MHz, CDCl3, δ): 6.09 (dd, J1 = 18 Hz, J2 = 4 Hz, 1H), 5.50 (d, J1 = 18 Hz, 1H), 1.53 (m, 1H), 1.26 (s, 12H), 0.81 (m, 2H), 0.54 (m, 2H); 13C NMR (100 MHz, CDCl3, δ): 158.5, 115.3, 82.9, 24.7, 17.0, 7.9; MS (ESI-TOF) m/z: 195.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C11H20BO2 [M + H]+ 195.1551, Found 195.1557. 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-N-Boc-3-amino1-propene (13g). White solid; 407 mg (yield 72%); mp 61.6–62.8 °C; 1H NMR (400 MHz, CDCl3, δ): 6.59 (dt, J1 = 18 Hz, J2 = 4 Hz, 1H), 5.59 (dt, J1 = 18 Hz, J2 = 6 Hz, 1H), 4.67 (s, 1H), 3.85 (m, 2H), 1.45 (s, 9H), 1.27 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 155.7, 149.4, 118.3, 83.3, 79.4, 44.0, 28.4, 24.8; MS (ESI-TOF) m/z: 284.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C14H27BNO4 [M + H]+ 284.2024, Found 284.2028.
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Organic & Biomolecular Chemistry 1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-trimethylsilylethene (13h). Colorless oil; 340 mg (yield 75%); 1H NMR (400 MHz, CDCl3, δ): 7.14 (d, J = 22 Hz, 1H), 6.26 (d, J = 22 Hz, 1H), 1.30 (s, 12H), 0.1 (s, 9H); 13C NMR (100 MHz, CDCl3, δ): 157.9, 83.4, 24.8, 1.9; MS (ESI-TOF) m/z: 227.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C11H24BO2Si [M + H]+ 227.1633, Found 227.1638. 1-Phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-butene (13i). Colorless oil; 433 mg (yield 84%); 1H NMR (400 MHz, CDCl3, δ): 7.36 (m, 4H), 7.28 (m, 2H), 2.46 (q, J = 7.6 Hz, 2H), 1.36 (s, 12H), 1.16 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3, δ): 141.4, 137.9, 129.0, 128.1, 127.1, 83.4, 24.8, 22.7, 14.7; MS (ESI-TOF) m/z: 259.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C16H24BO2Si [M + H]+ 259.1864, Found 259.1868.
Acknowledgements Financial support of this work was provided by Shanghai Saijia Chemicals Ltd., Shanghai Municipal Science and Technology Commission (Project no. 12430501300), and the Innovation Team Building Project of Pharmaceutical Engineering in Shanghai (XKZZ1205).
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Organic & Biomolecular Chemistry
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