Organocatalytic Asymmetric Tandem Conjugate Addition–Protonation of Azlactones to N-Itaconimides

Abstract

An unprecedented catalytic asymmetric reaction between azlactones and N-itaconimides has been developed. In the presence of an l-tert-leucine-based urea–tertiary amine Brønsted base catalyst, the tandem conjugate addition–protonation products could be attained in moderate yields with excellent enantio- and diastereoselectivities (up to 99% ee and >20:1 dr). The method provides an efficient approach to access valuable chiral γ-tertiary amine substituted succinimides containing nonadjacent stereocenters.

Key words

asymmetric organocatalysis - azlactones - N-itaconimides - succinimides - nonadjacent stereocenters - chiral Brønsted bases

• References and Notes

• 1a Katritzky AR, Yao J, Qi M, Chou Y, Sikora DJ, Davis S. Heterocycles 1998; 48: 2677-2677
• 1b Ballini R, Bosica G, Cioci G, Fiorini D, Petrini M. Tetrahedron 2003; 59: 3603-3603

For selected examples of N-maleimides in asymmetric synthesis, see:
• 2a Bartoli G, Bosco M, Carlone A, Cavalli A, Locatelli M, Mazzanti A, Ricci P, Sambri L, Melchiorre P. Angew. Chem. Int. Ed. 2006; 45: 4966-4966
• 2b Shen J, Nguyen TT, Goh Y.-P, Ye W, Fu X, Xu J, Tan C.-H. J. Am. Chem. Soc. 2006; 128: 13692-13692
• 2c Ye W, Jiang Z, Zhao Y, Goh LM. S, Leow D, Soh Y.-T, Tan C.-H. Adv. Synth. Catal. 2007; 349: 2454-2454
• 2d Zu L, Xie H, Li H, Wang J, Jiang W, Wang W. Adv. Synth. Catal. 2007; 349: 1882-1882
• 2e Jiang Z, Pan Y, Zhao Y, Ma T, Lee R, Yang Y, Huang K.-W, Wong MW, Tan C.-H. Angew. Chem. Int. Ed. 2009; 48: 3627-3627
• 2f Soh JY.-T, Tan C.-H. J. Am. Chem. Soc. 2009; 131: 6904-6904
• 2g Li X, Hu S, Xi Z, Zhang L, Luo S, Cheng J.-P. J. Org. Chem. 2010; 75: 8697-8697
• 2h Liao Y.-H, Liu X.-L, Wu Z.-J, Cun L.-F, Zhang X.-M, Yuan W.-C. Org. Lett. 2010; 12: 2896-2896
• 2i Liao Y.-H, Liu X.-L, Wu Z.-J, Du X.-L, Zhang X.-M, Yuan W.-C. Adv. Synth. Catal. 2011; 353: 1720-1720
• 2j Li L, Chen W, Yang W, Pan Y, Liu H, Tan C.-H, Jiang Z. Chem. Commun. 2012; 48: 5124-5124
• 2k Yang X, Wang C, Ni Q, Enders D. Synthesis 2012; 44: 2601-2601
• 2l Manna MS, Mukherjee S. Chem. Eur. J. 2012; 18: 15277-15277
• 2m Avila A, Chinchilla R, Najera C. Tetrahedron: Asymmetry 2012; 23: 1625-1625
• 2n Guo Y.-L, Jia L.-N, Peng L, Qi L.-W, Zhou J, Tian F, Xu X.-Y, Wang L.-X. RSC Adv. 2013; 3: 16973-16973
• 2o Wu L, Wang Y, Song H, Tang L, Zhou Z, Tang C. ChemCatChem 2014; 6: 649-649
• 2p Qiu S, Lee R, Zhu B, Coote ML, Zhao X, Jiang Z. J. Org. Chem. 2016; 81: 8061-8061
• 2q Li J, Qiu S, Ye X, Zhu B, Liu H, Jiang Z. J. Org. Chem. 2016; 81: 11916-11916
• 3a Wang J, Liu H, Fan Y, Yang Y, Jiang Z, Tan C.-H. Chem. Eur. J. 2010; 16: 12534-12534
• 3b Yang W, Tan D, Li L, Han Z, Yan L, Huang K.-W, Tan C.-H, Jiang Z. J. Org. Chem. 2012; 77: 6600-6600
• 4a Leow D, Lin S, Chittimalla SK, Fu X, Tan C.-H. Angew. Chem. Int. Ed. 2008; 47: 5641-5641
• 4b Liu Y, Zhang W. Angew. Chem. Int. Ed. 2013; 52: 2203-2203
• 4c Liu X, Ye X, Bureš F, Liu H, Jiang Z. Angew. Chem. Int. Ed. 2015; 54: 11443-11443
• 4d Zhu B, Lee R, Li J, Ye X, Hong S.-N, Qiu S, Coote ML, Jiang Z. Angew. Chem. Int. Ed. 2016; 55: 1299-1299
• 4e Qiu S, Tan C.-H, Jiang Z. Beilstein J. Org. Chem. 2016; 12: 2293-2293
• 5 Yan L, Yang W, Li L, Shen Y, Jiang Z. Chin. J. Chem. 2011; 29: 1906-1906

For selected examples of building nonadjacent stereocenters in asymmetric catalysis, see:
• 6a Wang B, Wu F, Wang Y, Liu X, Deng L. J. Am. Chem. Soc. 2007; 129: 768-768
• 6b Li X, Luo S, Cheng J.-P. Chem. Eur. J. 2010; 16: 14290-14290
• 6c Repka LM, Ni J, Reisman SE. J. Am. Chem. Soc. 2010; 132: 14418-14418
• 6d Duan S.-W, An J, Chen J.-R, Xiao W.-J. Org. Lett. 2011; 13: 2290-2290
• 6e Kieffer ME, Repka LM, Reisman SE. J. Am. Chem. Soc. 2012; 134: 5131-5131

For selected reviews, see:
• 7a Fisk JS, Mosey RA, Tepe JJ. Chem. Soc. Rev. 2007; 36: 1432-1432
• 7b Alba A.-NR, Rios R. Chem. Asian J. 2011; 6: 720-720
• 7c Piperno A, Scala A, Risitano F, Grassi G. Curr. Org. Chem. 2014; 18: 2691-2691
• 7d de Castro PP, Carpanez AG, Amarante GW. Chem. Eur. J. 2016; 22: 10294-10294
• 7e Hosamani B, Ribeiro MF, da Silva Júnior EN, Namboothiri IN. N. Org. Biomol. Chem. 2016; 14: 6913-6913

For selected examples, see:
• 7f Uraguchi D, Ueki Y, Ooi T. J. Am. Chem. Soc. 2008; 130: 14088-14088
• 7g Terada M, Tanaka H, Sorimachi K. J. Am. Chem. Soc. 2009; 131: 3430-3430
• 7h Trost BM, Czabaniuk LC. J. Am. Chem. Soc. 2012; 134: 5778-5778
• 7i Geng Z.-C, Chen X, Zhang J.-X, Li N, Chen J, Huang X.-F, Zhang S.-Y, Tao J.-C, Wang X.-W. Eur. J. Org. Chem. 2013; 4738-4738
• 7j Zhang S.-Y, Ruan G.-Y, Geng Z.-C, Li N.-K, Lv M, Wang Y, Wang X.-W. Org. Biomol. Chem. 2015; 13: 5698-5698
• 8a Zhu Z, McKittrick B, Sun Z.-Y, Ye YC, Voigt JH, Strickland C, Smith EM, Stamford A, Greenlee WJ. Jr, Mazzola RD, Caldwell J, Cumming JN, Wang L, Wu Y, Iserloh U, Liu X, Huang Y, Li G, Pan J, Misiaszek JA, Guo T, Le TX. H, Saionz KW, Babu SD, Hunter RC, Morris ML, Gu H, Qian G, Tadesse D, Lai G, Guo J, Qu C, Shao Y. WO 2008103351, 2008
• 8b Zhu Z, McKittrick B, Sun Z.-Y, Ye YC, Voigt JH, Strickland CO, Smith EM, Stamford A, Greenlee WJ, Mazzola RD, Caldwell JP, Cumming JN, Wang L, Wu Y, Iserloh U, Liu X, Guo T, Le TX. E, Saionz KW, Babu SD, Hunter RC, Morris ML, Gu H, Qian G, Tadesse D, Huang Y, Li G, Pan J, Misiaszek JA, Lai G, Duo J, Qu C, Shao Y. US 20080200445, 2008
• 9 Mohr JT, Hong AY, Stoltz BM. Nat. Chem. 2009; 1: 359-359
• 10a Han Z, Chen W, Dong S, Yang C, Liu H, Pan Y, Yan L, Jiang Z. Org. Lett. 2012; 14: 4670-4670
• 10b Zhang W, Tan D, Lee R, Tong G, Chen W, Qi B, Huang K.-W, Tan C.-H, Jiang Z. Angew. Chem. Int. Ed. 2012; 51: 10069-10069
• 10c Yang Y, Moinodeen F, Chin W, Ma T, Jiang Z, Tan C.-H. Org. Lett. 2012; 14: 4762-4762
• 10d Han Z, Yang W, Tan C.-H, Jiang Z. Adv. Synth. Catal. 2013; 355: 1505-1505
• 10e Zhu B, Zhang W, Lee R, Han Z, Yang W, Tan D, Huang K.-W, Jiang Z. Angew. Chem. Int. Ed. 2013; 52: 6666-6666
• 10f Qiao B, An Y, Liu Q, Yang W, Liu H, Shen J, Yan L, Jiang Z. Org. Lett. 2013; 15: 2358-2358
• 10g Chen W, Jing Z, Chin KF, Qiao B, Zhao Y, Yan L, Tan C.-H, Jiang Z. Adv. Synth. Catal. 2014; 356: 1292-1292
• 10h Qiao B, Liu X, Duan S, Yan L, Jiang Z. Org. Lett. 2014; 16: 672-672
• 10i Liu Q, Qiao B, Chin KF, Tan C.-H, Jiang Z. Adv. Synth. Catal. 2014; 356: 3777-3777
• 10j Xu M, Qiao B, Duan S, Liu H, Jiang Z. Tetrahedron 2014; 70: 8696-8696
• 10k Huang L, Li J, Zhao Y, Ye X, Liu Y, Yan L, Tan C.-H, Liu H, Jiang Z. J. Org. Chem. 2015; 80: 8933-8933
• 10l Duan S, Li S, Ye X, Du N.-N, Tan C.-H, Jiang Z. J. Org. Chem. 2015; 80: 7770-7770
• 10m Bai X, Jing Z, Liu Q, Ye X, Zhang G, Zhao X, Jiang Z. J. Org. Chem. 2015; 80: 12686-12686
• 10n Jiao L, Zhao X, Liu H, Ye X, Li Y, Jiang Z. Org. Chem. Front. 2016; 3: 470-470
• 10o Jing Z, Bai X, Chen W, Zhang G, Zhu B, Jiang Z. Org. Lett. 2016; 18: 260-260
• 10p Hou X, Jing Z, Bai X, Jiang Z. Molecules 2016; 21: 842-842
• 10q Zhu B, Qiu S, Li J, Coote ML, Lee R, Jiang Z. Chem. Sci. 2016; 7: 6060-6060
• 10r Bai X, Zeng G, Shao T, Jiang Z. Angew. Chem. Int. Ed. 2017; 56-56 : in press; DOI: 10.1002/anie.201700190
• 10s See also refs. 2p,q and 4d,e.
• 11 Andrés JM, Manzano R, Pedrosa R. Chem. Eur. J. 2008; 14: 5116-5116
• 12a Gao Y, Ren Q, Wang L, Wang J. Chem. Eur. J. 2010; 16: 13068-13068
• 12b Du Z, Siau W.-Y, Wang J. Tetrahedron Lett. 2011; 52: 6137-6137
• 12c Han X, Kwiatkowski J, Xue F, Huang K.-W, Lu Y. Angew. Chem. Int. Ed. 2009; 48: 7604-7604
• 12d Luo J, Wang H, Han X, Xu L.-W, Kwiatkowski J, Huang K.-W, Lu Y. Angew. Chem. Int. Ed. 2011; 50: 1861-1861
• 12e Manzano R, Andrés JM, Álvarez R, Muruzábal MD, de Lera ÁR, Pedrosa R. Chem. Eur. J. 2011; 17: 5931-5931
• 12f See also refs. 2q, 10b,e,f.
• 13 Zhao X, Zhu B, Jiang Z. Synlett 2015; 26: 2216-2216
• 14 CCDC 1523943 (3a) and CCDC 1524124 (4a) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 15 General Procedure for the Synthesis of 3 Azlactone 1 (0.20 mmol, 2.0 equiv), catalyst CAT-4 (0.01 mmol, 0.1 equiv), and CaCl₂ (0.15 mmol, 1.5 equiv) were dissolved in CH₂Cl₂ (2.0 mL) and stirred at 25 °C for 10 min. Then N-itaconimide 2 (0.2 mmol, 2 equiv) was added. The reaction mixture was stirred at 25 °C and monitored by TLC. Upon complete consumption of itaconimide 2, the reaction mixture was loaded onto a short silica gel column, followed by separation with flash chromatography using gradient elution with PE–EtOAc mixtures (15:1 to 3:1). Removal of the solvent in vacuo afforded product 3. (R)-3-{[(S)-4-Methyl-5-oxo-2-phenyl-4,5-dihydrooxazol-4-yl]-methyl}-1-phenylpyrrolidine-2,5-dione (3a) White solid; 68% yield; 96% ee; >20:1 dr. ¹H NMR (300 MHz, CDCl₃): δ = 8.00 (d, J = 7.5 Hz, 2 H), 7.62–7.47 (m, 6 H), 7.13 (d, J = 7.8 Hz, 2 H), 2.93–2.86 (m, 2 H), 2.76–2.69 (m, 2 H), 2.25–2.18 (m, 1 H), 1.59 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 179.7, 177.1, 174.5, 160.7, 133.2, 132.4, 130.6, 129.0, 128.0, 127.8, 125.5, 122.5, 68.6, 39.4, 37.2, 35.6, 33.9. ESI-HRMS: m/z calcd for C₂₁H₁₉N₂O₄ 363.1345; found: 363.1350 [M + H]⁺. The ee was determined by HPLC analysis. CHIRALPAK AD-H (4.6 mm i.d. × 250 mm); hexane–2-PrOH, 80:20; flow rate 1.0 mL/min; 25 °C; 254 nm; t _R = 18.7 min (major) and 27.0 min (minor).