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nBu4NI-Catalyzed oxidative imidation of ketones with imides: synthesis of a-amino ketones† Yunhe Lv, Yan Li, Tao Xiong, Yu Lu, Qun Liu and Qian Zhang*
Received 21st November 2013, Accepted 8th January 2014 DOI: 10.1039/c3cc48887j www.rsc.org/chemcomm
nBu4NI-Catalyzed oxidative imidation of ketones and imides for the synthesis of a-amino ketones were realized for the first time. The methodology is characterized by its wide substrate scope even for acetone with readily available phthalimide, saccharin and succinimide, which opens a new pathway for direct imidation of ketones.
a-Amino ketones are an important class of biologically relevant molecules.1 Additionally, these compounds are useful precursors for the synthesis of heterocycles2 and 1,2-amino alcohols.3 a-Amino ketones are traditionally prepared by the substitution reaction of a-halo/hydroxyl ketones with nucleophilic nitrogen sources4 or a-amination of carbonyl compounds with electrophilic nitrogen sources.5 For the synthesis of a-amino ketones via a nucleophilic amination reaction, prefunctionalization of the a-position of ketones is needed (for example, Scheme 1, path a).4 For an electrophilic amination reaction, pre-preparation of electrophilic nitrogen sources is required (for example, Scheme 1, path b).5 Obviously, the most simple and efficient route for the synthesis of a-amino ketones might be the oxidative C–N bond coupling reaction between N–H bonds in nitrogen sources and sp3 C–H bonds in the a-position of ketones. In this communication, nBu4NI-catalyzed direct oxidative imidation reactions of various simple ketones, including the parent acetone, with a diverse range of imides, such as phthalimide, saccharin and succinimide, were realized for the first time (Scheme 1, path c). As part of our continuing interest in employing various nitrogen sources for efficient construction of C–N bonds directly from C–H bonds,6 the reaction between acetone and N-fluorobenzenesulfonimide (NFSI) was tested. In fact, we discovered that NFSI could be utilized as an effecient radical nitrogen source for benzylic C–H amination6b and aminative difunctionalization of alkenes,6g and the nitrogen-based radical addition reactions of NFSI to aromatic rings were also realized by Ritter and co-workers very recently.7 Initially, we
Department of Chemistry, Northeast Normal University, Changchun, 130024, China. E-mail: [email protected]; Fax: +86-431-5099759 † Electronic supplementary information (ESI) available. See DOI: 10.1039/ c3cc48887j
This journal is © The Royal Society of Chemistry 2014
Scheme 1 Methods for the synthesis of a-amino ketones from ketone derivatives.
were pleased to find that with acetone as the solvent, the aminated product 3a was obtained in 46% yield with Pd(OAc)2 as the catalyst and 1,10-phenanthroline as the ligand (eqn (1)). Then some other potential radical nitrogen sources8 containing N–H bonds as well as catalytic systems were investigated. Recently, Ishihara and co-workers9 reported a remarkable n-butylammonium iodide (nBu4NI) catalyzed enantioselective oxidative cycloetherification and a-oxyacylation of carbonyl compounds with carboxylic acids. To our delight, with saccharin 2b as the nitrogen source and acetone as the solvent, the combination of nBu4NI (0.2 equiv.) and tert-butylhydroperoxide (TBHP, 2 equiv.) was extraordinarily efficient and gave the desired aminated product 3b in 95% yield (Table 1, entry 1). Remarkably, it was not necessary to use acetone as the solvent in this reaction. Ethyl acetate and dichloromethane (DCM) were effective in providing 3b in 91% and 71% yields, respectively (Table 1, entries 2 and 3). Instead of nBu4NI, the use of some other catalysts such as NaI, NH4I, nBu4NBr, nBu4NCl, I2, and NIS decreased the yields of 3b dramatically, or no 3b was observed (Table 1, entries 5–10). As shown in Table 1, TBHP was the most effective peroxide in the process. Other oxidants such as K2S2O8, di-tert-butylperoxide (TBP), O2 and 30% H2O2 did not perform well (Table 1, entries 11–14). 3b could also be obtained in 71% yield when 70% TBHP was employed as the peroxide (Table 1, entry 15). In addition, when the reaction was performed at 70 1C or 100 1C, 3b was isolated in 55% or 82% yield. No 3b was observed when either nBu4NI or TBHP was absent. It should be noted that this imidation reaction was performed under environmentally benign conditions (with tert-butyl alcohol and water
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as by-products) without utilizing metal or stoichiometric amounts of hypervalent iodine(III) species.6 f,10
Table 3
Imidation of ketones 1 with saccharin 2aa,b
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(1)
To explore the generality and scope of the direct a-imidation of acetone, a variety of imide nitrogen sources were investigated. As shown in Table 2, sulfimides with different substituents at the aromatic ring could be converted to the desired products 3c–f in high to excellent yields. To our delight, phthalimide could also give the a-amino carbonyl compound 3g in 81% yield. In addition, substituted phthalimides reacted smoothly with acetone to give products 3h–j in high to excellent yields. Furthermore, succinimide (2k) and Table 1
Optimization of the reaction conditionsa
a
Entry
Oxidantb
Catalyst
Solvent
Yieldc (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP K2S2O8 TBP O2 H2O2e TBHP f
nBu4NI nBu4NI nBu4NI nBu4NI NaI NH4I nBu4NBr nBu4NCl I2 NIS nBu4NI nBu4NI nBu4NI nBu4NI nBu4NI
Acetone EtOAc DCM EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc
95 91 71 54d Trace 63 47 53 0 0 Trace Trace 0 0 71
a
Reaction conditions: 1a (1.5 mmol), 2b (0.3 mmol), oxidant (0.6 mmol), catalyst (0.06 mmol), solvent (3.0 mL), 130 1C, 3 h. b TBHP (5.5 M in decane). c Yield of the isolated product. d 1a (0.9 mmol). e H2O2 (30% in water). f TBHP (70% in water).
Table 2
Imidation of acetone with imides 2a,b
a
Standard reaction conditions: 1a (1.5 mmol), 2 (0.3 mmol), TBHP (0.6 mmol, 5.5 M in decane), nBu4NI (0.06 mmol), EtOAc (3.0 mL), 130 1C, 3 h. b Yield of the isolated products.
2368 | Chem. Commun., 2014, 50, 2367--2369
Standard reaction conditions: 1 (1.5 mmol), 2b (0.3 mmol), TBHP (0.6 mmol, 5.5 M in decane), nBu4NI (0.06 mmol), EtOAc (3.0 mL), 130 1C, 3 h. b Yield of the isolated products.
1,2-cyclohexanedicarboximide (2l) were effective substrates under these conditions, the yields of the corresponding 3k and 3l were up to 92% and 94%, respectively. Remarkably, starting from 1,8-naphthalimide (2m), the imidation product 3m was obtained in 85% yield. As we know naphthalimide derivatives possess interesting properties, and they could be widely used as tunable dye lasers, polymerizable materials, fluorescent chemical sensors and electroluminescent organic diodes in thin films.11 However, amines such as pyrrolidine and morpholine did not give the desired aminated products. To further explore the potential of this efficient imidation reaction, several ketones as well as 1,3-dicarbonyl compounds were examined as substrates to react with saccharin (2b) under the optimized reaction conditions. Aryl ketones with various functional groups were effective. Aryl ketone substrates bearing electrondonating substituents were converted into the corresponding products in higher yields compared with substrates with electronwithdrawing substituents on the aromatic ring (Table 3, 4b–k). Halosubstituted aryl ketones (1c, 1d, 1j–l) were tolerated in the a-imidation reaction, and could be very useful for further transformations. In addition, starting from 1-acetylnaphthalene (1m), 2-acetylthiophene (1n) and 2-acetylfuran (1o), 4m, 4n and 4o could be obtained in good yields. Cycloketones such as cyclopentanone (1p), cyclohexanone (1q), cycloheptanone (1r) and 4-methylcyclohexanone (1s) were also effective in providing 4p–s in 48–69% yields. 1,3-Diketones 1t and 1u gave the corresponding a-amino carbonyl compounds in high yields. Next, the chemo- and regio-selectivity of this imidation reaction were tested. Although from 1-cyclopropylethanone (1v) and 2-methylpentan-3-one (1w), the only aminated product 4v and 4w was obtained in 90% and 73% yields, respectively, for other ketones tested (1x–z), the corresponding chemo- and regioselective imidation products were observed. Imidation products 4x, 4x0 and 4x00 were obtained starting from butan-2-one (1x).
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For pentan-3-one (1y), imidation and oxidation products 4y and 4y0 were obtained in 77% and 20% yields, respectively. 4-Methylpentan2-one (1z) gave the regio-isomers 4z and 4z0 . Several control experiments were performed to probe the reaction mechanism (see ESI†). The competitive imidations involving 1a and its deuterated derivative 1a-d6 were performed and obvious kinetic isotope effect (kH/kD = 5/1) was observed. This result showed that the enol form of ketone was formed during this imidation process.12 When the radical scavenger 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO, 2.0 equiv.) was added to the imidation reaction of pentan-3-one (1y) under the optimal conditions, after 3 h, a trace amount of 4y was observed. Starting from acetone, 3b and 5 were obtained in 47% and 21% yields, respectively (eqn (2)). Furthermore, when 3b reacted with saccharin (1.0 equiv.) and TEMPO (2.0 equiv.) in the presence of nBu4NI (0.2 equiv.) and TBHP (2.0 equiv.) for 9 h, 5 was obtained in 37% yield along with 51% 3b recovered (eqn (3)). This result showed that the radical addition of enol to provide the a-functionalized ketone was possible in this catalytic system. Interestingly, no reaction occurred for the above reaction but without adding 1.0 equiv. of saccharin. In addition, ESI-MS analysis of the reaction system of 1a (see ESI,† reacted for 40 minutes) and 50 mL of the mixture was used for the negative ion ESI analysis in CH3CN, which showed the presence of I2. In the work of Wei,13 [IO2] was detected in the nBu4NI–H2O2 reaction system. However, as described in Table 1, entry 14, no desired imidation product was formed with H2O2 as the oxidant. Therefore, we do not propose that [nBu4N]+[IO] or [nBu4N]+[IO2] generated in situ from nBu4NI and a co-oxidant involved in this catalytic cycle.9 No reactions occur between acetone and saccharin under the optimal conditions but with stoichiometric NIS or molecular iodine (I2) instead of using nBu4NI as the catalyst and TBHP as the oxidant.14 Furthermore, no ketone iodinated products were detected in these imidation reactions and morpholine and pyrrolidine were not effective for this imidation reaction only with the starting materials recovered. Combined with the result that no a-ketoamides15a were obtained, we do not agree with the nuleophilic amination mechanism via in situ generated a-iodoketones in this reaction.15 At present we prefer a radical amination mechanism (see ESI†),16 although further studies on the reaction mechanism are underway.
(2)
(3)
In conclusion, we have described the first example of an nBu4NIcatalyzed C–N cross coupling imidation reaction of sp3 C–H bonds of simple ketones and N–H bonds in imides with TBHP as an environmentally benign oxidant. Various ketones including the simplest acetone and a diverse range of imides such as phthalimide, saccharin and succinimide were efficient, which made this imidation reaction very attractive. This methodology promises to provide a new pathway for direct imidation of ketones.
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Financial support for this research by the SRFDP (20110043110002), the NNSFC (21372041, 21302017) and the Fundamental Research Funds for the Central Universities (11GJHZ001 and 11QNJJ015) is greatly acknowledged.
Notes and references 1 (a) A. Lee, L. Huang and J. Ellman, J. Am. Chem. Soc., 1999, 121, 9907; (b) T. A. Rano, T. Timkey, E. P. Peterson, J. Rotonda, D. W. Nicholson, J. W. Becker, K. T. Chapman and N. A. Thornberry, Chem. Biol., 1997, 4, 149; (c) R. W. Marquis, Y. Ru, D. S. Yamashita, H. J. Oh, J. Yen, S. K. Thompson, T. J. Carr, M. A. Levy, T. A. Tomaszek, C. F. Ijames, W. W. Smith, B. Zhao, C. A. Janson, S. Abdel-Meguid, K. J. D’Alessio, M. S. McQueeney and D. F. Veber, Bioorg. Med. Chem., 1999, 7, 581. 2 (a) T. N. Sorrell and W. E. Allen, J. Org. Chem., 1994, 59, 1589; (b) P. Langer and A. Bodtke, Tetrahedron Lett., 2003, 44, 5965; (c) D. E. Frantz, L. Morency, A. Soheili, J. A. Murry, E. J. J. Grabowski and R. D. Tillyer, Org. Lett., 2004, 6, 843. 3 For reviews on the utility and synthesis of 1,2-amino alcohols from a-amino ketones, see: (a) D. J. Ager, I. Prakash and D. R. Schaad, Chem. Rev., 1996, 96, 835; (b) M. T. Reetz, Angew. Chem., Int. Ed., 1991, 30, 1531. 4 L. E. Fisher and J. M. Muchowski, Org. Prep. Proced. Int., 1990, 22, 399. 5 (a) E. Erdik, Tetrahedron, 2004, 60, 8747; (b) P. Selig, Angew. Chem., Int. Ed., 2013, 52, 7080; (c) A. M. R. Smith and K. K. Hii, Chem. Rev., 2011, 111, 1637. 6 (a) T. Xiong, Y. Li, L. Mao, Q. Zhang and Q. Zhang, Chem. Commun., 2012, 48, 2246; (b) Z. Ni, Q. Zhang, T. Xiong, Y. Zheng, Y. Li, H. Zhang, J. Zhang and Q. Liu, Angew. Chem., Int. Ed., 2012, 51, 1244; (c) K. Sun, Y. Li, T. Xiong, J. Zhang and Q. Zhang, J. Am. Chem. Soc., 2011, 133, 1694; (d) T. Xiong, Y. Li, Y. Lv and Q. Zhang, Chem. Commun., 2010, 46, 6831; (e) Y. Lv, Y. Li, T. Xiong, W. Pu, H. Zhang, K. Sun, Q. Liu and Q. Zhang, Chem. Commun., 2013, 49, 6439; ( f ) L. Mao, Y. Li, T. Xiong, K. Sun and Q. Zhang, J. Org. Chem., 2013, 78, 733; (g) H. Zhang, W. Pu, T. Xiong, Y. Li, X. Zhou, K. Sun, Q. Liu and Q. Zhang, Angew. Chem., Int. Ed., 2013, 52, 2529. 7 G. B. Boursalian, M.-Y. Ngai, K. N. Hojczyk and T. Ritter, J. Am. Chem. Soc., 2013, 136, 13278. 8 Selected examples for generation of imidyl radicals from saccharin and phthalimide, see: (a) H. Togo, Y. Hoshina, T. Muraki, H. Nakayama and M. Yokoyama, J. Org. Chem., 1998, 63, 5193; (b) H. Hettler, Adv. Heterocycl. ´nchez-Sa ´nchez, E. Pe ´rez-Inestrosa, R. Garcı´aChem., 1973, 15, 233; (c) C. Sa Segura and R. Suau, Tetrahedron, 2002, 58, 7267. 9 (a) M. Uyanik, H. Okamoto, T. Yasui and K. Ishihara, Science, 2010, 328, 1376; (b) M. Uyanik, D. Suzuki, T. Yasui and K. Ishihara, Angew. Chem., Int. Ed., 2011, 50, 5331. 10 Intramolecular oxidative amination using stoichiometric amount of hypervalent iodine(III) species: (a) Y. Ye, H. Wang and R. Fan, Org. Lett., 2010, 12, 2802; (b) Y. Sun and R. Fan, Chem. Commun., 2010, 46, 6834; amination of ketones with nitrogen sources containing a N–I(III) bond: ˜iz, Angew. Chem., Int. Ed., (c) J. A. Souto, C. Martı´nez, I. Velilla and K. Mun 2013, 52, 1324; (d) L. Hadjiarapoglou, S. Spyroudis and A. Varvoglis, Synthesis, 1983, 207; (e) M. Papadopoulou and A. Varvoglis, J. Chem. Res., Synop., 1984, 166. 11 (a) J. L. G. Coronado, E. Martı´n, L. A. Montero, J. L. G. Fierro and J. M. Garcı´a de la Vega, J. Phys. Chem. A, 2007, 111, 9724; (b) M. K. Hargreaves, J. G. Pritchard and H. R. Dave, Chem. Rev., 1970, 70, 439; (c) S. Banerjee, E. B. Veale, C. M. Phelan, S. A. Murphy, G. M. Tocci, L. J. Gillespie, D. O. Frimannsson, J. M. Kelly and T. Gunnlaugsson, Chem. Soc. Rev., 2013, 42, 1601. 12 R. A. Lynch, S. P. Vincenti, Y. T. Lin, L. D. Smucker and S. C. Subba Rao, J. Am. Chem. Soc., 1972, 94, 8351. 13 C. Zhu and Y. Wei, ChemSusChem, 2011, 4, 1082. 14 J.-S. Tian, K. W. J. Ng, J.-R. Wong and T.-P. Loh, Angew. Chem., Int. Ed., 2012, 51, 9105. 15 (a) M. Lamani and K. R. Prabhu, Chem.–Eur. J., 2012, 18, 14638; (b) X. Zhang and L. Wang, Green Chem., 2012, 14, 2141; (c) W. Wei, Y. Shao, H. Y. Hu, F. Zhang, C. Zhang, Y. Xu and X. Wan, J. Org. Chem., 2012, 77, 7157. 16 (a) M. Uyanik and K. Ishihara, ChemCatChem, 2012, 4, 177; (b) P. Finkbeiner and B. J. Nachtsheim, Synthesis, 2013, 979; (c) Z. J. Liu, J. Zhang, S. L. Chen, E. Shi, Y. Xu and X. B. Wan, Angew. Chem., Int. Ed., 2012, 51, 3231; (d) B. Tan, N. Toda and C. F. Barbas III, Angew. Chem., Int. Ed., 2012, 51, 12538; (e) W. Mai, H. Wang, Z. Li, J. Yuan, Y. Xiao, L. Yang, P. Mao and L. Qu, Chem. Commun., 2012, 48, 10117.
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nBu4NI-Catalyzed oxidative imidation of ketones with imides: synthesis of a-amino ketones† Yunhe Lv, Yan Li, Tao Xiong, Yu Lu, Qun Liu and Qian Zhang*
Received 21st November 2013, Accepted 8th January 2014 DOI: 10.1039/c3cc48887j www.rsc.org/chemcomm
nBu4NI-Catalyzed oxidative imidation of ketones and imides for the synthesis of a-amino ketones were realized for the first time. The methodology is characterized by its wide substrate scope even for acetone with readily available phthalimide, saccharin and succinimide, which opens a new pathway for direct imidation of ketones.
a-Amino ketones are an important class of biologically relevant molecules.1 Additionally, these compounds are useful precursors for the synthesis of heterocycles2 and 1,2-amino alcohols.3 a-Amino ketones are traditionally prepared by the substitution reaction of a-halo/hydroxyl ketones with nucleophilic nitrogen sources4 or a-amination of carbonyl compounds with electrophilic nitrogen sources.5 For the synthesis of a-amino ketones via a nucleophilic amination reaction, prefunctionalization of the a-position of ketones is needed (for example, Scheme 1, path a).4 For an electrophilic amination reaction, pre-preparation of electrophilic nitrogen sources is required (for example, Scheme 1, path b).5 Obviously, the most simple and efficient route for the synthesis of a-amino ketones might be the oxidative C–N bond coupling reaction between N–H bonds in nitrogen sources and sp3 C–H bonds in the a-position of ketones. In this communication, nBu4NI-catalyzed direct oxidative imidation reactions of various simple ketones, including the parent acetone, with a diverse range of imides, such as phthalimide, saccharin and succinimide, were realized for the first time (Scheme 1, path c). As part of our continuing interest in employing various nitrogen sources for efficient construction of C–N bonds directly from C–H bonds,6 the reaction between acetone and N-fluorobenzenesulfonimide (NFSI) was tested. In fact, we discovered that NFSI could be utilized as an effecient radical nitrogen source for benzylic C–H amination6b and aminative difunctionalization of alkenes,6g and the nitrogen-based radical addition reactions of NFSI to aromatic rings were also realized by Ritter and co-workers very recently.7 Initially, we
Department of Chemistry, Northeast Normal University, Changchun, 130024, China. E-mail: [email protected]; Fax: +86-431-5099759 † Electronic supplementary information (ESI) available. See DOI: 10.1039/ c3cc48887j
This journal is © The Royal Society of Chemistry 2014
Scheme 1 Methods for the synthesis of a-amino ketones from ketone derivatives.
were pleased to find that with acetone as the solvent, the aminated product 3a was obtained in 46% yield with Pd(OAc)2 as the catalyst and 1,10-phenanthroline as the ligand (eqn (1)). Then some other potential radical nitrogen sources8 containing N–H bonds as well as catalytic systems were investigated. Recently, Ishihara and co-workers9 reported a remarkable n-butylammonium iodide (nBu4NI) catalyzed enantioselective oxidative cycloetherification and a-oxyacylation of carbonyl compounds with carboxylic acids. To our delight, with saccharin 2b as the nitrogen source and acetone as the solvent, the combination of nBu4NI (0.2 equiv.) and tert-butylhydroperoxide (TBHP, 2 equiv.) was extraordinarily efficient and gave the desired aminated product 3b in 95% yield (Table 1, entry 1). Remarkably, it was not necessary to use acetone as the solvent in this reaction. Ethyl acetate and dichloromethane (DCM) were effective in providing 3b in 91% and 71% yields, respectively (Table 1, entries 2 and 3). Instead of nBu4NI, the use of some other catalysts such as NaI, NH4I, nBu4NBr, nBu4NCl, I2, and NIS decreased the yields of 3b dramatically, or no 3b was observed (Table 1, entries 5–10). As shown in Table 1, TBHP was the most effective peroxide in the process. Other oxidants such as K2S2O8, di-tert-butylperoxide (TBP), O2 and 30% H2O2 did not perform well (Table 1, entries 11–14). 3b could also be obtained in 71% yield when 70% TBHP was employed as the peroxide (Table 1, entry 15). In addition, when the reaction was performed at 70 1C or 100 1C, 3b was isolated in 55% or 82% yield. No 3b was observed when either nBu4NI or TBHP was absent. It should be noted that this imidation reaction was performed under environmentally benign conditions (with tert-butyl alcohol and water
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as by-products) without utilizing metal or stoichiometric amounts of hypervalent iodine(III) species.6 f,10
Table 3
Imidation of ketones 1 with saccharin 2aa,b
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(1)
To explore the generality and scope of the direct a-imidation of acetone, a variety of imide nitrogen sources were investigated. As shown in Table 2, sulfimides with different substituents at the aromatic ring could be converted to the desired products 3c–f in high to excellent yields. To our delight, phthalimide could also give the a-amino carbonyl compound 3g in 81% yield. In addition, substituted phthalimides reacted smoothly with acetone to give products 3h–j in high to excellent yields. Furthermore, succinimide (2k) and Table 1
Optimization of the reaction conditionsa
a
Entry
Oxidantb
Catalyst
Solvent
Yieldc (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP K2S2O8 TBP O2 H2O2e TBHP f
nBu4NI nBu4NI nBu4NI nBu4NI NaI NH4I nBu4NBr nBu4NCl I2 NIS nBu4NI nBu4NI nBu4NI nBu4NI nBu4NI
Acetone EtOAc DCM EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc
95 91 71 54d Trace 63 47 53 0 0 Trace Trace 0 0 71
a
Reaction conditions: 1a (1.5 mmol), 2b (0.3 mmol), oxidant (0.6 mmol), catalyst (0.06 mmol), solvent (3.0 mL), 130 1C, 3 h. b TBHP (5.5 M in decane). c Yield of the isolated product. d 1a (0.9 mmol). e H2O2 (30% in water). f TBHP (70% in water).
Table 2
Imidation of acetone with imides 2a,b
a
Standard reaction conditions: 1a (1.5 mmol), 2 (0.3 mmol), TBHP (0.6 mmol, 5.5 M in decane), nBu4NI (0.06 mmol), EtOAc (3.0 mL), 130 1C, 3 h. b Yield of the isolated products.
2368 | Chem. Commun., 2014, 50, 2367--2369
Standard reaction conditions: 1 (1.5 mmol), 2b (0.3 mmol), TBHP (0.6 mmol, 5.5 M in decane), nBu4NI (0.06 mmol), EtOAc (3.0 mL), 130 1C, 3 h. b Yield of the isolated products.
1,2-cyclohexanedicarboximide (2l) were effective substrates under these conditions, the yields of the corresponding 3k and 3l were up to 92% and 94%, respectively. Remarkably, starting from 1,8-naphthalimide (2m), the imidation product 3m was obtained in 85% yield. As we know naphthalimide derivatives possess interesting properties, and they could be widely used as tunable dye lasers, polymerizable materials, fluorescent chemical sensors and electroluminescent organic diodes in thin films.11 However, amines such as pyrrolidine and morpholine did not give the desired aminated products. To further explore the potential of this efficient imidation reaction, several ketones as well as 1,3-dicarbonyl compounds were examined as substrates to react with saccharin (2b) under the optimized reaction conditions. Aryl ketones with various functional groups were effective. Aryl ketone substrates bearing electrondonating substituents were converted into the corresponding products in higher yields compared with substrates with electronwithdrawing substituents on the aromatic ring (Table 3, 4b–k). Halosubstituted aryl ketones (1c, 1d, 1j–l) were tolerated in the a-imidation reaction, and could be very useful for further transformations. In addition, starting from 1-acetylnaphthalene (1m), 2-acetylthiophene (1n) and 2-acetylfuran (1o), 4m, 4n and 4o could be obtained in good yields. Cycloketones such as cyclopentanone (1p), cyclohexanone (1q), cycloheptanone (1r) and 4-methylcyclohexanone (1s) were also effective in providing 4p–s in 48–69% yields. 1,3-Diketones 1t and 1u gave the corresponding a-amino carbonyl compounds in high yields. Next, the chemo- and regio-selectivity of this imidation reaction were tested. Although from 1-cyclopropylethanone (1v) and 2-methylpentan-3-one (1w), the only aminated product 4v and 4w was obtained in 90% and 73% yields, respectively, for other ketones tested (1x–z), the corresponding chemo- and regioselective imidation products were observed. Imidation products 4x, 4x0 and 4x00 were obtained starting from butan-2-one (1x).
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For pentan-3-one (1y), imidation and oxidation products 4y and 4y0 were obtained in 77% and 20% yields, respectively. 4-Methylpentan2-one (1z) gave the regio-isomers 4z and 4z0 . Several control experiments were performed to probe the reaction mechanism (see ESI†). The competitive imidations involving 1a and its deuterated derivative 1a-d6 were performed and obvious kinetic isotope effect (kH/kD = 5/1) was observed. This result showed that the enol form of ketone was formed during this imidation process.12 When the radical scavenger 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO, 2.0 equiv.) was added to the imidation reaction of pentan-3-one (1y) under the optimal conditions, after 3 h, a trace amount of 4y was observed. Starting from acetone, 3b and 5 were obtained in 47% and 21% yields, respectively (eqn (2)). Furthermore, when 3b reacted with saccharin (1.0 equiv.) and TEMPO (2.0 equiv.) in the presence of nBu4NI (0.2 equiv.) and TBHP (2.0 equiv.) for 9 h, 5 was obtained in 37% yield along with 51% 3b recovered (eqn (3)). This result showed that the radical addition of enol to provide the a-functionalized ketone was possible in this catalytic system. Interestingly, no reaction occurred for the above reaction but without adding 1.0 equiv. of saccharin. In addition, ESI-MS analysis of the reaction system of 1a (see ESI,† reacted for 40 minutes) and 50 mL of the mixture was used for the negative ion ESI analysis in CH3CN, which showed the presence of I2. In the work of Wei,13 [IO2] was detected in the nBu4NI–H2O2 reaction system. However, as described in Table 1, entry 14, no desired imidation product was formed with H2O2 as the oxidant. Therefore, we do not propose that [nBu4N]+[IO] or [nBu4N]+[IO2] generated in situ from nBu4NI and a co-oxidant involved in this catalytic cycle.9 No reactions occur between acetone and saccharin under the optimal conditions but with stoichiometric NIS or molecular iodine (I2) instead of using nBu4NI as the catalyst and TBHP as the oxidant.14 Furthermore, no ketone iodinated products were detected in these imidation reactions and morpholine and pyrrolidine were not effective for this imidation reaction only with the starting materials recovered. Combined with the result that no a-ketoamides15a were obtained, we do not agree with the nuleophilic amination mechanism via in situ generated a-iodoketones in this reaction.15 At present we prefer a radical amination mechanism (see ESI†),16 although further studies on the reaction mechanism are underway.
(2)
(3)
In conclusion, we have described the first example of an nBu4NIcatalyzed C–N cross coupling imidation reaction of sp3 C–H bonds of simple ketones and N–H bonds in imides with TBHP as an environmentally benign oxidant. Various ketones including the simplest acetone and a diverse range of imides such as phthalimide, saccharin and succinimide were efficient, which made this imidation reaction very attractive. This methodology promises to provide a new pathway for direct imidation of ketones.
This journal is © The Royal Society of Chemistry 2014
Financial support for this research by the SRFDP (20110043110002), the NNSFC (21372041, 21302017) and the Fundamental Research Funds for the Central Universities (11GJHZ001 and 11QNJJ015) is greatly acknowledged.
Notes and references 1 (a) A. Lee, L. Huang and J. Ellman, J. Am. Chem. Soc., 1999, 121, 9907; (b) T. A. Rano, T. Timkey, E. P. Peterson, J. Rotonda, D. W. Nicholson, J. W. Becker, K. T. Chapman and N. A. Thornberry, Chem. Biol., 1997, 4, 149; (c) R. W. Marquis, Y. Ru, D. S. Yamashita, H. J. Oh, J. Yen, S. K. Thompson, T. J. Carr, M. A. Levy, T. A. Tomaszek, C. F. Ijames, W. W. Smith, B. Zhao, C. A. Janson, S. Abdel-Meguid, K. J. D’Alessio, M. S. McQueeney and D. F. Veber, Bioorg. Med. Chem., 1999, 7, 581. 2 (a) T. N. Sorrell and W. E. Allen, J. Org. Chem., 1994, 59, 1589; (b) P. Langer and A. Bodtke, Tetrahedron Lett., 2003, 44, 5965; (c) D. E. Frantz, L. Morency, A. Soheili, J. A. Murry, E. J. J. Grabowski and R. D. Tillyer, Org. Lett., 2004, 6, 843. 3 For reviews on the utility and synthesis of 1,2-amino alcohols from a-amino ketones, see: (a) D. J. Ager, I. Prakash and D. R. Schaad, Chem. Rev., 1996, 96, 835; (b) M. T. Reetz, Angew. Chem., Int. Ed., 1991, 30, 1531. 4 L. E. Fisher and J. M. Muchowski, Org. Prep. Proced. Int., 1990, 22, 399. 5 (a) E. Erdik, Tetrahedron, 2004, 60, 8747; (b) P. Selig, Angew. Chem., Int. Ed., 2013, 52, 7080; (c) A. M. R. Smith and K. K. Hii, Chem. Rev., 2011, 111, 1637. 6 (a) T. Xiong, Y. Li, L. Mao, Q. Zhang and Q. Zhang, Chem. Commun., 2012, 48, 2246; (b) Z. Ni, Q. Zhang, T. Xiong, Y. Zheng, Y. Li, H. Zhang, J. Zhang and Q. Liu, Angew. Chem., Int. Ed., 2012, 51, 1244; (c) K. Sun, Y. Li, T. Xiong, J. Zhang and Q. Zhang, J. Am. Chem. Soc., 2011, 133, 1694; (d) T. Xiong, Y. Li, Y. Lv and Q. Zhang, Chem. Commun., 2010, 46, 6831; (e) Y. Lv, Y. Li, T. Xiong, W. Pu, H. Zhang, K. Sun, Q. Liu and Q. Zhang, Chem. Commun., 2013, 49, 6439; ( f ) L. Mao, Y. Li, T. Xiong, K. Sun and Q. Zhang, J. Org. Chem., 2013, 78, 733; (g) H. Zhang, W. Pu, T. Xiong, Y. Li, X. Zhou, K. Sun, Q. Liu and Q. Zhang, Angew. Chem., Int. Ed., 2013, 52, 2529. 7 G. B. Boursalian, M.-Y. Ngai, K. N. Hojczyk and T. Ritter, J. Am. Chem. Soc., 2013, 136, 13278. 8 Selected examples for generation of imidyl radicals from saccharin and phthalimide, see: (a) H. Togo, Y. Hoshina, T. Muraki, H. Nakayama and M. Yokoyama, J. Org. Chem., 1998, 63, 5193; (b) H. Hettler, Adv. Heterocycl. ´nchez-Sa ´nchez, E. Pe ´rez-Inestrosa, R. Garcı´aChem., 1973, 15, 233; (c) C. Sa Segura and R. Suau, Tetrahedron, 2002, 58, 7267. 9 (a) M. Uyanik, H. Okamoto, T. Yasui and K. Ishihara, Science, 2010, 328, 1376; (b) M. Uyanik, D. Suzuki, T. Yasui and K. Ishihara, Angew. Chem., Int. Ed., 2011, 50, 5331. 10 Intramolecular oxidative amination using stoichiometric amount of hypervalent iodine(III) species: (a) Y. Ye, H. Wang and R. Fan, Org. Lett., 2010, 12, 2802; (b) Y. Sun and R. Fan, Chem. Commun., 2010, 46, 6834; amination of ketones with nitrogen sources containing a N–I(III) bond: ˜iz, Angew. Chem., Int. Ed., (c) J. A. Souto, C. Martı´nez, I. Velilla and K. Mun 2013, 52, 1324; (d) L. Hadjiarapoglou, S. Spyroudis and A. Varvoglis, Synthesis, 1983, 207; (e) M. Papadopoulou and A. Varvoglis, J. Chem. Res., Synop., 1984, 166. 11 (a) J. L. G. Coronado, E. Martı´n, L. A. Montero, J. L. G. Fierro and J. M. Garcı´a de la Vega, J. Phys. Chem. A, 2007, 111, 9724; (b) M. K. Hargreaves, J. G. Pritchard and H. R. Dave, Chem. Rev., 1970, 70, 439; (c) S. Banerjee, E. B. Veale, C. M. Phelan, S. A. Murphy, G. M. Tocci, L. J. Gillespie, D. O. Frimannsson, J. M. Kelly and T. Gunnlaugsson, Chem. Soc. Rev., 2013, 42, 1601. 12 R. A. Lynch, S. P. Vincenti, Y. T. Lin, L. D. Smucker and S. C. Subba Rao, J. Am. Chem. Soc., 1972, 94, 8351. 13 C. Zhu and Y. Wei, ChemSusChem, 2011, 4, 1082. 14 J.-S. Tian, K. W. J. Ng, J.-R. Wong and T.-P. Loh, Angew. Chem., Int. Ed., 2012, 51, 9105. 15 (a) M. Lamani and K. R. Prabhu, Chem.–Eur. J., 2012, 18, 14638; (b) X. Zhang and L. Wang, Green Chem., 2012, 14, 2141; (c) W. Wei, Y. Shao, H. Y. Hu, F. Zhang, C. Zhang, Y. Xu and X. Wan, J. Org. Chem., 2012, 77, 7157. 16 (a) M. Uyanik and K. Ishihara, ChemCatChem, 2012, 4, 177; (b) P. Finkbeiner and B. J. Nachtsheim, Synthesis, 2013, 979; (c) Z. J. Liu, J. Zhang, S. L. Chen, E. Shi, Y. Xu and X. B. Wan, Angew. Chem., Int. Ed., 2012, 51, 3231; (d) B. Tan, N. Toda and C. F. Barbas III, Angew. Chem., Int. Ed., 2012, 51, 12538; (e) W. Mai, H. Wang, Z. Li, J. Yuan, Y. Xiao, L. Yang, P. Mao and L. Qu, Chem. Commun., 2012, 48, 10117.
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