ChemComm View Article Online
Published on 08 April 2014. Downloaded by FLORIDA ATLANTIC UNIVERSITY on 22/10/2014 17:40:37.
COMMUNICATION
Cite this: Chem. Commun., 2014, 50, 5760 Received 11th March 2014, Accepted 4th April 2014
View Journal | View Issue
Novel tartrate-derived guanidine-catalyzed highly enantio- and diastereoselective Michael addition of 3-substituted oxindoles to nitroolefins† Liwei Zou, Xiaoze Bao, Yuanyuan Ma, Yuming Song, Jingping Qu and Baomin Wang*
DOI: 10.1039/c4cc01817f www.rsc.org/chemcomm
The Michael addition of 3-substituted oxindoles to nitroolefins was catalyzed by a novel tartrate-derived guanidine in high yield with excellent diastereo- and enantioselectivity. This method showed an extraordinarily broad substrate scope in terms of both reaction partners.
The frequent occurrence of the 3,3-disubstituted oxindole scaffold in alkaloid natural products and pharmaceutically relevant compounds has stimulated significant synthetic effort toward the construction of this privileged structural motif.1 In this regard, a variety of strategies have been developed depending on the varying starting materials used, which generally include anilides,2 isatins,3 3-alkylidene oxindoles4 and 3-substituted oxindoles.5–8 Among these methods, those with 3-substituted oxindoles have garnered intense recent interest since they have proven to be extremely straightforward and versatile, particularly in terms of the catalytic asymmetric assembly of C3 quaternary oxindoles. Since the initial report by Barbas III and co-workers on the catalytic asymmetric Michael addition of 3-sustituted oxindoles to nitroolefins by a chiral thiourea organocatalyst,7a a handful of catalyst systems have been evaluated with this reaction.7,8 The challenge and advantage of this process involves the simultaneous creation of vicinal tertiary and all-carbon quaternary stereocenters, and the incorporation of a nitro group in the product as a versatile synthetic handle for further elaboration.9 Aside from thiourea-based chiral organocatalysts as the majority of the promoters,7a,c,d,g,h,l,m other catalysts reported include cinchona alkaloids,7e, j a phase-transfer catalyst,7b an indane-based aminoalcohol,7f and a proline-derived secondary amine.7i In addition, two reports concerning chiral Lewis acid catalysis were also documented.8 Despite these achievements, few catalyst systems can afford both a broad substrate scope and an excellent stereocontrol. Therefore, given the significant value of this conjugate addition, State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024, P. R. China. E-mail: [email protected] † Electronic supplementary information (ESI) available. CCDC 990860. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4cc01817f
5760 | Chem. Commun., 2014, 50, 5760--5762
the introduction of more efficient catalysts demonstrating broad substrate generality with excellent stereoselectivity is still highly desirable. Chiral guanidines represent a prominent catalyst class in the field of organocatalysis, which have enabled a broad array of asymmetric transformations.10 Despite various chiral guanidine catalysts introduced thus far, the development in this area is still hampered by the lack of a skeleton that is both synthetically easily accessible and readily tunable in terms of steric and electronic properties. Given the abundant availability and ready diversification of tartaric acid and derivatives thereof, very recently we developed a novel library of chiral guanidines featuring a tartaric acid skeleton, which showed remarkable catalytic activity toward the enantioselective a-hydroxylation of b-dicarbonyl compounds.11 To further expand the utility of this library of guanidines, herein we report the conjugate addition of 3-substituted oxindoles to nitroolefins by the tartrate-based guanidine with a broad substrate scope and excellent stereocontrol (Fig. 1). Initial experiments were focused on the identification of optimal reaction conditions (Table 1). Thus, guanidine catalysts were evaluated with the Michael addition of N-Boc 3-benzyloxindole 9a to b-nitrostyrene 10a as the model reaction. The tartrate-based
Fig. 1
The guanidine catalysts used in this work.
This journal is © The Royal Society of Chemistry 2014
View Article Online
Published on 08 April 2014. Downloaded by FLORIDA ATLANTIC UNIVERSITY on 22/10/2014 17:40:37.
Communication
ChemComm
Table 1
Optimization of the reaction conditionsa
Entry
Cat.
Solvent
t (h)
Yieldb (%)
drc
1 2 3 4 5 6 7 8 9 10 11 12 13 14d 15e 16 f
1 2 3 4 5 6 7 8 4 4 4 4 4 4 4 4
Tol Tol Tol Tol Tol Tol Tol Tol CH2Cl2 EA THF MTBE Et2O Et2O Et2O Et2O
1 1 17 16 3 2 5 min 5 min 23 7 7 5 4 6 12 41
72 77 70 72 73 87 81 79 92 95 74 89 93 97 99 99
89/11 88/12 95/5 95/5 66/34 94/6 41/59 44/56 77/23 91/9 89/11 92/8 94/6 96/4 98/2 99/1
Table 2
eed (%) 37 33 16 77 61 48 1 22 47 51 16 79 81 87 91 94
a
Unless otherwise noted, reactions were conducted with 3-substitued oxindole 9a (0.1 mmol), catalyst (10 mol%) and nitroalkene 10a (1.2 equiv.) in solvent (1 mL) at 25 1C. b Isolated yield. c Determined by chiral HPLC analysis (Chiralcel AD-H). d 0 1C. e 20 1C. f 40 1C.
guanidine 1 displaying a benzyl group afforded the product in good yield with good diastereoselectivity and modest enantioselectivity for the major diastereomer (entry 1). Comparable results were observed with guanidine 2 bearing a 4-tert-butyl benzyl group (entry 2). While 2,6-diisopropyl aniline-derived guanidine 3 exhibited respectable dr but poor enantioselectivity, its 3,5-di-tert-butyl congener 4 afforded a very promising ee of 77% with the same diastereoselectivity (entries 3 and 4). Although a modest dr of 66 : 34 was observed with guanidine 5 derived from a chiral aminoalcohol, it is interesting to note that a reversal in the sense of the enantioselectivity for the major diastereomer occurred (entry 5). The ketal moiety of the guanidine catalyst was also found to markedly influence the stereoselectivity, as can be seen from the fact that guanidine 6 displaying a cyclohexanone ketal afforded a drastically decreased ee of 48% compared to 4 (entry 6). Furthermore, two known guanidines, the widely used bicyclic guanidine 7 introduced by Tan12 and the easily accessible proline-based guanidine 8 developed by Feng,13 were also investigated, but both afforded poor diastereo- and enantioselectivities (entries 7 and 8). With guanidine 4 as the catalyst of choice, the reaction media were screened (entries 9–13), which led to the identification of diethyl ether as the optimum solvent, affording 93% yield, 96 : 4 dr and 81% ee in 4 hours at room temperature. The stereoselectivity was found to be sensitive to the reaction temperature (entries 14–16), thus by lowering the temperature to 40 1C an excellent stereocontrol of 99 : 1 dr and 94% ee was achieved. With the optimal reaction conditions established, the substrate generality with respect to nitroolefins was then explored (Table 2). Initially, nitrostyrene derivatives displaying electronically diverse phenyl rings with varying substitution patterns were
This journal is © The Royal Society of Chemistry 2014
Substrate generality for nitroolefinsa
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14
10a 10b 10c 10d 10e 10f 10g 10h 10i 10j 10k 10l 10m 10n
R
t (h)
Yieldb (%)
drc
eec (%)
Ph p-FC6H4 p-ClC6H4 p-BrC6H4 p-CF3C6H4 o-ClC6H4 3,4-Cl2C6H3 p-MeC6H4 p-iPrC6H4 p-MeOC6H4 2-Furanyl 2-Thiophenyl C6H5CH2 n-Pr
41 47 47 50 24 47 24 49 48 71 40 36 216 240
99 93 89 98 91 94 93 96 99 92 92 97 91 82
99/1 98/2 98/2 98/2 97/3 92/8 99/1 499/1 97/3 99/1 99/1 99/1 499/1 499/1
94 93 93 92 93 91 97 95 94 94 90 499 97 98
a
Unless otherwise noted, reactions were conducted with 3-substitued oxindole 9a (0.2 mmol), catalyst 4 (10 mol%) and nitroalkene 10 (1.2 equiv.) in diethyl ether (2 mL). b Isolated yield. c Determined by chiral HPLC analysis.
subjected to the reaction conditions. Gratifyingly, all these Michael acceptors afforded uniformly high product yields with excellent diastereo- and enantioselectivities. Moreover, heteroaryl nitroolefins also performed well, with 2-thiophenyl nitroolefin delivering virtually pure stereoisomers (entry 12). Notably, alkyl nitroolefins also participated in this reaction with excellent stereocontrol although much longer reaction times were needed to maintain high yields (entries 13 and 14). The absolute configuration of product 11ad was determined to be R at the quaternary carbon and S at the other one by X-ray crystallographic analysis (entry 4, for details see the ESI†), and those of others were assigned by analogy. Following the establishment of the broad generality of nitroolefins, the substrate scope with respect to 3-substituted oxindoles was next investigated (Table 3). Similarly, a wide array of oxindoles were proved to be suitable substrates. Various 3-benzyl and heterobenzyl oxindoles reacted smoothly with a selection of aryl nitroolefins, affording the adducts in high yields with excellent diastereo- and enantioselectivities. 3-Phenyl oxindole was also accommodated albeit with a marginally decreased enantioselectivity. Furthermore, 3-alkyl oxindoles underwent the Michael addition with the same levels of efficiency and stereoselectivity. Hence, the tartrate-based guanidine catalyst exhibits extraordinarily broad substrate generality with respect to both 3-substituted oxindoles and nitroolefins, which stands in sharp contrast to the catalyst systems reported so far. In summary, a novel tartrate-derived guanidine was demonstrated to be a highly competent organocatalyst for the asymmetric conjugate addition of 3-substituted oxindoles to nitroolefins. The Michael adduct was obtained in high yield with excellent diastereoand enantioselectivities. This catalyst system revealed very broad generality in terms of both 3-substituted oxindole and
Chem. Commun., 2014, 50, 5760--5762 | 5761
View Article Online
ChemComm
Published on 08 April 2014. Downloaded by FLORIDA ATLANTIC UNIVERSITY on 22/10/2014 17:40:37.
Table 3
Substrate generality for 3-substitued oxindolesa
a
Unless otherwise noted, reactions were conducted with 3-substitued oxindole 9 (0.2 mmol), catalyst 4 (10 mol%) and nitroalkene 10 (1.2 equiv.) in diethyl ether (2 mL). b Isolated yield. c Determined by chiral HPLC analysis. d The absolute configuration of 11ia was determined by comparison of the optical rotation and retention time with literature data (ref. 7b).
nitroolefin substrates, as a broad array of aryl, alkyl, and benzyl substituents on both components were well accommodated. Studies toward further expanding the catalytic applications of the tartrate-derived guanidines for other asymmetric transformations are currently underway in our laboratory. We thank the National Natural Science Foundation of China (No. 21076035, 20972022), the Program for New Century Excellent Talents in University (NCET-11-0053), the Fundamental Research Funds for the Central Universities (DUT13ZD202), and the Science and Technology Department of Liaoning Province (No. 20102032) for support of this work.
Notes and references 1 For reviews, see: (a) C. Marti and E. M. Carreira, Eur. J. Org. Chem., 2003, 2209; (b) A. B. Dounay and L. E. Overman, Chem. Rev., 2003, 103, 2945; (c) C. V. Galliford and K. A. Scheidt, Angew. Chem., Int. Ed., 2007, 46, 8748; (d) F. Zhou, Y.-L. Liu and J. Zhou, Adv. Synth. Catal., 2010, 352, 1381; (e) J. E. M. N. Klein and R. J. K. Taylor, Eur. J. Org. Chem., 2011, 6821; ( f ) G. S. Singh and Z. Y. Desta, Chem. Rev., 2012, 112, 6104; ( g) K. Shen, X. Liu, L. Lin and X. Feng, Chem. Sci., 2012, 3, 327; (h) R. Dalpozzo, G. Bartoli and G. Bencivenni, Chem. Soc. Rev., 2012, 41, 7247.
5762 | Chem. Commun., 2014, 50, 5760--5762
Communication 2 (a) A. Perry and R. J. K. Taylor, Chem. Commun., 2009, 3249; (b) J. E. M. N. Klein, A. Perry, D. S. Pugh and R. J. K. Taylor, Org. Lett., 2010, 12, 3446; (c) W. Fu, F. Xu, Y. Fu, M. Zhu, J. Yu, C. Xu and D. Zou, J. Org. Chem., 2013, 78, 12202; (d) S.-L. Zhou, L.-N. Guo, H. Wang and X.-H. Duan, Chem. – Eur. J., 2013, 19, 12970. 3 (a) G. Luppi, P. G. Cozzi, M. Monari, B. Kaptein, Q. B. Broxterman and C. Tomasini, J. Org. Chem., 2005, 70, 7418; (b) L. Liu, S. Zhang, F. Xue, G. Lou, H. Zhang, S. Ma, W. Duan and W. Wang, Chem. – Eur. J., 2011, 17, 7791; (c) Q. Ren, J. Huang, L. Wang, W. Li, H. Liu, X. Jiang and J. Wang, ACS Catal., 2012, 2, 2622; (d) I. Saidalimu, X. Fang, X.-P. He, J. Liang, X. Yang and F. Wu, Angew. Chem., Int. Ed., 2013, 52, 5566; (e) B. Zhu, W. Zhang, R. Lee, Z. Han, W. Yang, D. Tan, K.-W. Huang and Z. Jiang, Angew. Chem., Int. Ed., 2013, 52, 6666; ( f ) D. Monge, A. M. ´lvarez, R. Ferna ˜a, E. Martı´n-Zamora, E. A ´ndez and J. M. Crespo-Pen Lassaletta, Chem. – Eur. J., 2013, 19, 8421; (g) Z. Duan, J. Han, P. Qian, Z. Zhang, Y. Wang and Y. Pan, Org. Biomol. Chem., 2013, 11, 6456; (h) A. Kumar and S. S. Chimni, Tetrahedron, 2013, 69, 5197. 4 (a) F. Pesciaioli, P. Righi, A. Mazzanti, G. Bartoli and G. Bencivenni, Chem. – Eur. J., 2011, 17, 2842; (b) C. Curti, G. Rassu, V. Zambrano, L. Pinna, G. Pelosi, A. Sartori, L. Battistini, F. Zanardi and G. Casiraghi, Angew. Chem., Int. Ed., 2012, 51, 6200. 5 (a) T. Ishimaru, N. Shibata, J. Nagai, S. Nakamura, T. Toru and S. Kanemasa, J. Am. Chem. Soc., 2006, 128, 16488; (b) D. Sano, K. Nagata and T. Itoh, Org. Lett., 2008, 10, 1593; (c) T. Bui, N. R. Candeias and C. F. Barbas III, J. Am. Chem. Soc., 2010, 132, 5574; (d) Z. Zhang, W. Zheng and J. C. Antilla, Angew. Chem., Int. Ed., 2011, 50, 1135; (e) Y. Yang, F. Moinodeen, W. Chin, T. Ma, Z. Jiang and C.-H. Tan, Org. Lett., 2012, 14, 4762. 6 (a) T. Zhang, L. Cheng, S. Hameed, L. Liu, D. Wang and Y.-J. Chen, Chem. Commun., 2011, 47, 6644; (b) L. Li, W. Chen, W. Yang, Y. Pan, H. Liu, C.-H. Tan and Z. Jiang, Chem. Commun., 2012, 48, 5124; (c) Y.-H. Liao, X.-L. Liu, Z.-J. Wu, X.-L. Du, X.-M. Zhang and W.-C. Yuan, Chem. – Eur. J., 2012, 18, 6679; (d) F. Zhong, X. Dou, X. Han, W. Yao, Q. Zhu, Y. Meng and Y. Lu, Angew. Chem., Int. Ed., 2013, 52, 943. 7 (a) T. Bui, S. Syed and C. F. Barbas III, J. Am. Chem. Soc., 2009, 131, 8758; (b) R. He, S. Shirakawa and K. Maruoka, J. Am. Chem. Soc., 2009, 131, 16620; (c) X. Li, B. Zhang, Z.-G. Xi, S. Luo and J.-P. Cheng, Adv. Synth. Catal., 2010, 352, 416; (d) M. Ding, F. Zhou, Z.-Q. Qian and J. Zhou, Org. Biomol. Chem., 2010, 8, 2912; (e) M. Ding, F. Zhou, Y.-L. Liu, C.-H. Wang, X.-L. Zhao and J. Zhou, Chem. Sci., 2011, 2, 2035; ( f ) X.-L. Liu, Z.-J. Wu, X.-L. Du, X.-M. Zhang and W.-C. Yuan, J. Org. Chem., 2011, 76, 4008; (g) X. Li, Y.-M. Li, F.-Z. Peng, S.-T. Wu, Z.-Q. Li, Z.-W. Sun, H.-B. Zhang and Z.-H. Shao, Org. Lett., 2011, 13, 6160; (h) Y.-M. Li, X. Li, F.-Z. Peng, Z.-Q. Li, S.-T. Wu, Z.-W. Sun, H.-B. Zhang and Z.-H. Shao, Org. Lett., 2011, 13, 6200; (i) C. Wang, X. Yang and D. Enders, Chem. – Eur. J., 2012, 18, 4832; ( j) K. Albertshofer, B. Tan and C. F. Barbas III, Org. Lett., 2012, 14, 1834; (k) W. Yang, J. Wang and D.-M. Du, Tetrahedron: Asymmetry, 2012, 23, 972; (l) B.-D. Cui, W.-Y. Han, Z.-J. Wu, X.-M. Zhang and W.-C. Yuan, J. Org. Chem., 2013, 78, 8833; (m) X. Dou, B. Zhou, W. Yao, F. Zhong, C. Jiang and Y. Lu, Org. Lett., 2013, 15, 4920. 8 (a) Y. Kato, M. Furutachi, Z. Chen, H. Mitsunuma, S. Matsunaga and M. Shibasaki, J. Am. Chem. Soc., 2009, 131, 9168; (b) Y.-Y. Han, Z.-J. Wu, W.-B. Chen, X.-L. Du, X.-M. Zhang and W.-C. Yuan, Org. Lett., 2011, 13, 5064. 9 O. M. Berner, L. Tedeschi and D. Enders, Eur. J. Org. Chem., 2002, 1877. 10 For recent reviews, see: (a) T. Ishikawa and T. Kumamoto, Synthesis, 2006, 737; (b) D. Leow and C.-H. Tan, Chem. – Asian J., 2009, 4, 488; (c) M. P. Coles, Chem. Commun., 2009, 3659; (d) Y. Sohtome and K. Nagasawa, Synlett, 2010, 1; (e) D. Leow and C.-H. Tan, Synlett, 2010, 1589; ( f ) T. Ishikawa, Chem. Pharm. Bull., 2010, 58, 1555; ( g) P. Selig, Synthesis, 2013, 703. 11 L. Zou, B. Wang, H. Mu, H. Zhang, Y. Song and J. Qu, Org. Lett., 2013, 15, 3106. 12 W. Ye, D. Leow, S. L. M. Goh, C.-T. Tan, C.-H. Chian and C.-H. Tan, Tetrahedron Lett., 2006, 47, 1007. 13 Z. Yu, X. Liu, L. Zhou, L. Lin and X. Feng, Angew. Chem., Int. Ed., 2009, 48, 5195.
This journal is © The Royal Society of Chemistry 2014
Published on 08 April 2014. Downloaded by FLORIDA ATLANTIC UNIVERSITY on 22/10/2014 17:40:37.
COMMUNICATION
Cite this: Chem. Commun., 2014, 50, 5760 Received 11th March 2014, Accepted 4th April 2014
View Journal | View Issue
Novel tartrate-derived guanidine-catalyzed highly enantio- and diastereoselective Michael addition of 3-substituted oxindoles to nitroolefins† Liwei Zou, Xiaoze Bao, Yuanyuan Ma, Yuming Song, Jingping Qu and Baomin Wang*
DOI: 10.1039/c4cc01817f www.rsc.org/chemcomm
The Michael addition of 3-substituted oxindoles to nitroolefins was catalyzed by a novel tartrate-derived guanidine in high yield with excellent diastereo- and enantioselectivity. This method showed an extraordinarily broad substrate scope in terms of both reaction partners.
The frequent occurrence of the 3,3-disubstituted oxindole scaffold in alkaloid natural products and pharmaceutically relevant compounds has stimulated significant synthetic effort toward the construction of this privileged structural motif.1 In this regard, a variety of strategies have been developed depending on the varying starting materials used, which generally include anilides,2 isatins,3 3-alkylidene oxindoles4 and 3-substituted oxindoles.5–8 Among these methods, those with 3-substituted oxindoles have garnered intense recent interest since they have proven to be extremely straightforward and versatile, particularly in terms of the catalytic asymmetric assembly of C3 quaternary oxindoles. Since the initial report by Barbas III and co-workers on the catalytic asymmetric Michael addition of 3-sustituted oxindoles to nitroolefins by a chiral thiourea organocatalyst,7a a handful of catalyst systems have been evaluated with this reaction.7,8 The challenge and advantage of this process involves the simultaneous creation of vicinal tertiary and all-carbon quaternary stereocenters, and the incorporation of a nitro group in the product as a versatile synthetic handle for further elaboration.9 Aside from thiourea-based chiral organocatalysts as the majority of the promoters,7a,c,d,g,h,l,m other catalysts reported include cinchona alkaloids,7e, j a phase-transfer catalyst,7b an indane-based aminoalcohol,7f and a proline-derived secondary amine.7i In addition, two reports concerning chiral Lewis acid catalysis were also documented.8 Despite these achievements, few catalyst systems can afford both a broad substrate scope and an excellent stereocontrol. Therefore, given the significant value of this conjugate addition, State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 116024, P. R. China. E-mail: [email protected] † Electronic supplementary information (ESI) available. CCDC 990860. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4cc01817f
5760 | Chem. Commun., 2014, 50, 5760--5762
the introduction of more efficient catalysts demonstrating broad substrate generality with excellent stereoselectivity is still highly desirable. Chiral guanidines represent a prominent catalyst class in the field of organocatalysis, which have enabled a broad array of asymmetric transformations.10 Despite various chiral guanidine catalysts introduced thus far, the development in this area is still hampered by the lack of a skeleton that is both synthetically easily accessible and readily tunable in terms of steric and electronic properties. Given the abundant availability and ready diversification of tartaric acid and derivatives thereof, very recently we developed a novel library of chiral guanidines featuring a tartaric acid skeleton, which showed remarkable catalytic activity toward the enantioselective a-hydroxylation of b-dicarbonyl compounds.11 To further expand the utility of this library of guanidines, herein we report the conjugate addition of 3-substituted oxindoles to nitroolefins by the tartrate-based guanidine with a broad substrate scope and excellent stereocontrol (Fig. 1). Initial experiments were focused on the identification of optimal reaction conditions (Table 1). Thus, guanidine catalysts were evaluated with the Michael addition of N-Boc 3-benzyloxindole 9a to b-nitrostyrene 10a as the model reaction. The tartrate-based
Fig. 1
The guanidine catalysts used in this work.
This journal is © The Royal Society of Chemistry 2014
View Article Online
Published on 08 April 2014. Downloaded by FLORIDA ATLANTIC UNIVERSITY on 22/10/2014 17:40:37.
Communication
ChemComm
Table 1
Optimization of the reaction conditionsa
Entry
Cat.
Solvent
t (h)
Yieldb (%)
drc
1 2 3 4 5 6 7 8 9 10 11 12 13 14d 15e 16 f
1 2 3 4 5 6 7 8 4 4 4 4 4 4 4 4
Tol Tol Tol Tol Tol Tol Tol Tol CH2Cl2 EA THF MTBE Et2O Et2O Et2O Et2O
1 1 17 16 3 2 5 min 5 min 23 7 7 5 4 6 12 41
72 77 70 72 73 87 81 79 92 95 74 89 93 97 99 99
89/11 88/12 95/5 95/5 66/34 94/6 41/59 44/56 77/23 91/9 89/11 92/8 94/6 96/4 98/2 99/1
Table 2
eed (%) 37 33 16 77 61 48 1 22 47 51 16 79 81 87 91 94
a
Unless otherwise noted, reactions were conducted with 3-substitued oxindole 9a (0.1 mmol), catalyst (10 mol%) and nitroalkene 10a (1.2 equiv.) in solvent (1 mL) at 25 1C. b Isolated yield. c Determined by chiral HPLC analysis (Chiralcel AD-H). d 0 1C. e 20 1C. f 40 1C.
guanidine 1 displaying a benzyl group afforded the product in good yield with good diastereoselectivity and modest enantioselectivity for the major diastereomer (entry 1). Comparable results were observed with guanidine 2 bearing a 4-tert-butyl benzyl group (entry 2). While 2,6-diisopropyl aniline-derived guanidine 3 exhibited respectable dr but poor enantioselectivity, its 3,5-di-tert-butyl congener 4 afforded a very promising ee of 77% with the same diastereoselectivity (entries 3 and 4). Although a modest dr of 66 : 34 was observed with guanidine 5 derived from a chiral aminoalcohol, it is interesting to note that a reversal in the sense of the enantioselectivity for the major diastereomer occurred (entry 5). The ketal moiety of the guanidine catalyst was also found to markedly influence the stereoselectivity, as can be seen from the fact that guanidine 6 displaying a cyclohexanone ketal afforded a drastically decreased ee of 48% compared to 4 (entry 6). Furthermore, two known guanidines, the widely used bicyclic guanidine 7 introduced by Tan12 and the easily accessible proline-based guanidine 8 developed by Feng,13 were also investigated, but both afforded poor diastereo- and enantioselectivities (entries 7 and 8). With guanidine 4 as the catalyst of choice, the reaction media were screened (entries 9–13), which led to the identification of diethyl ether as the optimum solvent, affording 93% yield, 96 : 4 dr and 81% ee in 4 hours at room temperature. The stereoselectivity was found to be sensitive to the reaction temperature (entries 14–16), thus by lowering the temperature to 40 1C an excellent stereocontrol of 99 : 1 dr and 94% ee was achieved. With the optimal reaction conditions established, the substrate generality with respect to nitroolefins was then explored (Table 2). Initially, nitrostyrene derivatives displaying electronically diverse phenyl rings with varying substitution patterns were
This journal is © The Royal Society of Chemistry 2014
Substrate generality for nitroolefinsa
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14
10a 10b 10c 10d 10e 10f 10g 10h 10i 10j 10k 10l 10m 10n
R
t (h)
Yieldb (%)
drc
eec (%)
Ph p-FC6H4 p-ClC6H4 p-BrC6H4 p-CF3C6H4 o-ClC6H4 3,4-Cl2C6H3 p-MeC6H4 p-iPrC6H4 p-MeOC6H4 2-Furanyl 2-Thiophenyl C6H5CH2 n-Pr
41 47 47 50 24 47 24 49 48 71 40 36 216 240
99 93 89 98 91 94 93 96 99 92 92 97 91 82
99/1 98/2 98/2 98/2 97/3 92/8 99/1 499/1 97/3 99/1 99/1 99/1 499/1 499/1
94 93 93 92 93 91 97 95 94 94 90 499 97 98
a
Unless otherwise noted, reactions were conducted with 3-substitued oxindole 9a (0.2 mmol), catalyst 4 (10 mol%) and nitroalkene 10 (1.2 equiv.) in diethyl ether (2 mL). b Isolated yield. c Determined by chiral HPLC analysis.
subjected to the reaction conditions. Gratifyingly, all these Michael acceptors afforded uniformly high product yields with excellent diastereo- and enantioselectivities. Moreover, heteroaryl nitroolefins also performed well, with 2-thiophenyl nitroolefin delivering virtually pure stereoisomers (entry 12). Notably, alkyl nitroolefins also participated in this reaction with excellent stereocontrol although much longer reaction times were needed to maintain high yields (entries 13 and 14). The absolute configuration of product 11ad was determined to be R at the quaternary carbon and S at the other one by X-ray crystallographic analysis (entry 4, for details see the ESI†), and those of others were assigned by analogy. Following the establishment of the broad generality of nitroolefins, the substrate scope with respect to 3-substituted oxindoles was next investigated (Table 3). Similarly, a wide array of oxindoles were proved to be suitable substrates. Various 3-benzyl and heterobenzyl oxindoles reacted smoothly with a selection of aryl nitroolefins, affording the adducts in high yields with excellent diastereo- and enantioselectivities. 3-Phenyl oxindole was also accommodated albeit with a marginally decreased enantioselectivity. Furthermore, 3-alkyl oxindoles underwent the Michael addition with the same levels of efficiency and stereoselectivity. Hence, the tartrate-based guanidine catalyst exhibits extraordinarily broad substrate generality with respect to both 3-substituted oxindoles and nitroolefins, which stands in sharp contrast to the catalyst systems reported so far. In summary, a novel tartrate-derived guanidine was demonstrated to be a highly competent organocatalyst for the asymmetric conjugate addition of 3-substituted oxindoles to nitroolefins. The Michael adduct was obtained in high yield with excellent diastereoand enantioselectivities. This catalyst system revealed very broad generality in terms of both 3-substituted oxindole and
Chem. Commun., 2014, 50, 5760--5762 | 5761
View Article Online
ChemComm
Published on 08 April 2014. Downloaded by FLORIDA ATLANTIC UNIVERSITY on 22/10/2014 17:40:37.
Table 3
Substrate generality for 3-substitued oxindolesa
a
Unless otherwise noted, reactions were conducted with 3-substitued oxindole 9 (0.2 mmol), catalyst 4 (10 mol%) and nitroalkene 10 (1.2 equiv.) in diethyl ether (2 mL). b Isolated yield. c Determined by chiral HPLC analysis. d The absolute configuration of 11ia was determined by comparison of the optical rotation and retention time with literature data (ref. 7b).
nitroolefin substrates, as a broad array of aryl, alkyl, and benzyl substituents on both components were well accommodated. Studies toward further expanding the catalytic applications of the tartrate-derived guanidines for other asymmetric transformations are currently underway in our laboratory. We thank the National Natural Science Foundation of China (No. 21076035, 20972022), the Program for New Century Excellent Talents in University (NCET-11-0053), the Fundamental Research Funds for the Central Universities (DUT13ZD202), and the Science and Technology Department of Liaoning Province (No. 20102032) for support of this work.
Notes and references 1 For reviews, see: (a) C. Marti and E. M. Carreira, Eur. J. Org. Chem., 2003, 2209; (b) A. B. Dounay and L. E. Overman, Chem. Rev., 2003, 103, 2945; (c) C. V. Galliford and K. A. Scheidt, Angew. Chem., Int. Ed., 2007, 46, 8748; (d) F. Zhou, Y.-L. Liu and J. Zhou, Adv. Synth. Catal., 2010, 352, 1381; (e) J. E. M. N. Klein and R. J. K. Taylor, Eur. J. Org. Chem., 2011, 6821; ( f ) G. S. Singh and Z. Y. Desta, Chem. Rev., 2012, 112, 6104; ( g) K. Shen, X. Liu, L. Lin and X. Feng, Chem. Sci., 2012, 3, 327; (h) R. Dalpozzo, G. Bartoli and G. Bencivenni, Chem. Soc. Rev., 2012, 41, 7247.
5762 | Chem. Commun., 2014, 50, 5760--5762
Communication 2 (a) A. Perry and R. J. K. Taylor, Chem. Commun., 2009, 3249; (b) J. E. M. N. Klein, A. Perry, D. S. Pugh and R. J. K. Taylor, Org. Lett., 2010, 12, 3446; (c) W. Fu, F. Xu, Y. Fu, M. Zhu, J. Yu, C. Xu and D. Zou, J. Org. Chem., 2013, 78, 12202; (d) S.-L. Zhou, L.-N. Guo, H. Wang and X.-H. Duan, Chem. – Eur. J., 2013, 19, 12970. 3 (a) G. Luppi, P. G. Cozzi, M. Monari, B. Kaptein, Q. B. Broxterman and C. Tomasini, J. Org. Chem., 2005, 70, 7418; (b) L. Liu, S. Zhang, F. Xue, G. Lou, H. Zhang, S. Ma, W. Duan and W. Wang, Chem. – Eur. J., 2011, 17, 7791; (c) Q. Ren, J. Huang, L. Wang, W. Li, H. Liu, X. Jiang and J. Wang, ACS Catal., 2012, 2, 2622; (d) I. Saidalimu, X. Fang, X.-P. He, J. Liang, X. Yang and F. Wu, Angew. Chem., Int. Ed., 2013, 52, 5566; (e) B. Zhu, W. Zhang, R. Lee, Z. Han, W. Yang, D. Tan, K.-W. Huang and Z. Jiang, Angew. Chem., Int. Ed., 2013, 52, 6666; ( f ) D. Monge, A. M. ´lvarez, R. Ferna ˜a, E. Martı´n-Zamora, E. A ´ndez and J. M. Crespo-Pen Lassaletta, Chem. – Eur. J., 2013, 19, 8421; (g) Z. Duan, J. Han, P. Qian, Z. Zhang, Y. Wang and Y. Pan, Org. Biomol. Chem., 2013, 11, 6456; (h) A. Kumar and S. S. Chimni, Tetrahedron, 2013, 69, 5197. 4 (a) F. Pesciaioli, P. Righi, A. Mazzanti, G. Bartoli and G. Bencivenni, Chem. – Eur. J., 2011, 17, 2842; (b) C. Curti, G. Rassu, V. Zambrano, L. Pinna, G. Pelosi, A. Sartori, L. Battistini, F. Zanardi and G. Casiraghi, Angew. Chem., Int. Ed., 2012, 51, 6200. 5 (a) T. Ishimaru, N. Shibata, J. Nagai, S. Nakamura, T. Toru and S. Kanemasa, J. Am. Chem. Soc., 2006, 128, 16488; (b) D. Sano, K. Nagata and T. Itoh, Org. Lett., 2008, 10, 1593; (c) T. Bui, N. R. Candeias and C. F. Barbas III, J. Am. Chem. Soc., 2010, 132, 5574; (d) Z. Zhang, W. Zheng and J. C. Antilla, Angew. Chem., Int. Ed., 2011, 50, 1135; (e) Y. Yang, F. Moinodeen, W. Chin, T. Ma, Z. Jiang and C.-H. Tan, Org. Lett., 2012, 14, 4762. 6 (a) T. Zhang, L. Cheng, S. Hameed, L. Liu, D. Wang and Y.-J. Chen, Chem. Commun., 2011, 47, 6644; (b) L. Li, W. Chen, W. Yang, Y. Pan, H. Liu, C.-H. Tan and Z. Jiang, Chem. Commun., 2012, 48, 5124; (c) Y.-H. Liao, X.-L. Liu, Z.-J. Wu, X.-L. Du, X.-M. Zhang and W.-C. Yuan, Chem. – Eur. J., 2012, 18, 6679; (d) F. Zhong, X. Dou, X. Han, W. Yao, Q. Zhu, Y. Meng and Y. Lu, Angew. Chem., Int. Ed., 2013, 52, 943. 7 (a) T. Bui, S. Syed and C. F. Barbas III, J. Am. Chem. Soc., 2009, 131, 8758; (b) R. He, S. Shirakawa and K. Maruoka, J. Am. Chem. Soc., 2009, 131, 16620; (c) X. Li, B. Zhang, Z.-G. Xi, S. Luo and J.-P. Cheng, Adv. Synth. Catal., 2010, 352, 416; (d) M. Ding, F. Zhou, Z.-Q. Qian and J. Zhou, Org. Biomol. Chem., 2010, 8, 2912; (e) M. Ding, F. Zhou, Y.-L. Liu, C.-H. Wang, X.-L. Zhao and J. Zhou, Chem. Sci., 2011, 2, 2035; ( f ) X.-L. Liu, Z.-J. Wu, X.-L. Du, X.-M. Zhang and W.-C. Yuan, J. Org. Chem., 2011, 76, 4008; (g) X. Li, Y.-M. Li, F.-Z. Peng, S.-T. Wu, Z.-Q. Li, Z.-W. Sun, H.-B. Zhang and Z.-H. Shao, Org. Lett., 2011, 13, 6160; (h) Y.-M. Li, X. Li, F.-Z. Peng, Z.-Q. Li, S.-T. Wu, Z.-W. Sun, H.-B. Zhang and Z.-H. Shao, Org. Lett., 2011, 13, 6200; (i) C. Wang, X. Yang and D. Enders, Chem. – Eur. J., 2012, 18, 4832; ( j) K. Albertshofer, B. Tan and C. F. Barbas III, Org. Lett., 2012, 14, 1834; (k) W. Yang, J. Wang and D.-M. Du, Tetrahedron: Asymmetry, 2012, 23, 972; (l) B.-D. Cui, W.-Y. Han, Z.-J. Wu, X.-M. Zhang and W.-C. Yuan, J. Org. Chem., 2013, 78, 8833; (m) X. Dou, B. Zhou, W. Yao, F. Zhong, C. Jiang and Y. Lu, Org. Lett., 2013, 15, 4920. 8 (a) Y. Kato, M. Furutachi, Z. Chen, H. Mitsunuma, S. Matsunaga and M. Shibasaki, J. Am. Chem. Soc., 2009, 131, 9168; (b) Y.-Y. Han, Z.-J. Wu, W.-B. Chen, X.-L. Du, X.-M. Zhang and W.-C. Yuan, Org. Lett., 2011, 13, 5064. 9 O. M. Berner, L. Tedeschi and D. Enders, Eur. J. Org. Chem., 2002, 1877. 10 For recent reviews, see: (a) T. Ishikawa and T. Kumamoto, Synthesis, 2006, 737; (b) D. Leow and C.-H. Tan, Chem. – Asian J., 2009, 4, 488; (c) M. P. Coles, Chem. Commun., 2009, 3659; (d) Y. Sohtome and K. Nagasawa, Synlett, 2010, 1; (e) D. Leow and C.-H. Tan, Synlett, 2010, 1589; ( f ) T. Ishikawa, Chem. Pharm. Bull., 2010, 58, 1555; ( g) P. Selig, Synthesis, 2013, 703. 11 L. Zou, B. Wang, H. Mu, H. Zhang, Y. Song and J. Qu, Org. Lett., 2013, 15, 3106. 12 W. Ye, D. Leow, S. L. M. Goh, C.-T. Tan, C.-H. Chian and C.-H. Tan, Tetrahedron Lett., 2006, 47, 1007. 13 Z. Yu, X. Liu, L. Zhou, L. Lin and X. Feng, Angew. Chem., Int. Ed., 2009, 48, 5195.
This journal is © The Royal Society of Chemistry 2014
