Copper-Catalyzed Three-Component Tandem Reactions for the Synthesis of β-Carboalkoxy-γ-lactams

Abstract

β-Carboalkoxy-γ-lactams were synthesized in high yields via copper-catalyzed three-component reactions of α,β-unsaturated dicarboxylate esters, aldimines, and a silane. The reaction proceeds in a tandem manner via conjugate reduction, Mannich reaction, and a subsequent lactamization. The method is attractive with regard to the flexible combination of easily available reactants, the mild conditions, and the high yields. It provides a concise synthetic route to functionalized lactams with a β-ester group.

Key words

tandem reaction - copper - catalysis - conjugate reduction - aldol addition - lactamization

• References and Notes

• 1 Barrett AG. M, Head J, Smith ML, Stock NS, White AJ. P, Williams DJ. J. Org. Chem. 1999; 64: 6005
• 2 Bergmann R, Gericke R. J. Med. Chem. 1990; 33: 492
• 3 Nájera C, Yus M. Tetrahedron: Asymmetry 1999; 10: 2245
• 4 Tanaka R, Nakatsuka T, Ishiguro M. Bioorg. Med. Chem. Lett. 1993; 3: 2299
• 5 Kar GK, Roy BC, Das Adhikari S, Ray JK, Brahma NK. Bioorg. Med. Chem. 1998; 6: 2397
• 6 Patra P, Kar GK. Tetrahedron Lett. 2014; 55: 326
• 7 Choi MK. W, Yu WY, Che CM. Org. Lett. 2005; 7: 1081
• 8 Chen C, Hu J, Su J, Tong X. Tetrahedron Lett. 2014; 55: 3229
• 9 Craig D, Hyland CJ. T, Ward SE. Chem. Commun. 2005; 3439
• 10 Abbas M, Neuhaus C, Krebs B, Westermann B. Synlett 2005; 473
• 11 Longmire JM, Wang B, Zhang X. J. Am. Chem. Soc. 2002; 124: 13400
• 12 Park J.-H, Ha J.-R, Oh S.-J, Kim J.-A, Shin D.-S, Won T.-J, Lam Y.-F, Ahn C. Tetrahedron Lett. 2005; 46: 1755
• 13 Suto Y, Kanai M, Shibasaki M. J. Am. Chem. Soc. 2007; 129: 500
• 14 Pohmakotr M, Yotapan N, Tuchinda P, Kuhakarn C, Reutrakul V. Tetrahedron 2007; 63: 4328
• 15 Pohmakotr M, Yotapan N, Tuchinda P, Kuhakarn C, Reutrakul V. J. Org. Chem. 2007; 72: 5016
• 16 Le Gall E, Sengmany S, Samb I, Benakrour S, Colin C, Pignon A, Leonel E. Org. Biomol. Chem. 2014; 12: 3423
• 17 Pohmakotr M, Komutkul T, Tuchinda P, Prabpai S, Kongsaeree P, Reutrakul V. Tetrahedron 2005; 61: 5311
• 18 Mori A, Fujita A, Nishihara Y, Hiyama T. Chem. Commun. 1997; 2159
• 19 Zheng A, Shan F, Li Z, Li Z, Jiang L. Chem. Pap. 2013; 67: 1271
• 20 Lipshutz BH, Chrisman W, Noson K, Papa P, Sclafani JA, Vivian RW, Keith JM. Tetrahedron 2000; 56: 2779
• 21 Baker BA, Bokovic ZV, Lipshutz BH. Org. Lett. 2008; 10: 289
• 22 Chiu P, Szeto C.-P, Geng Z, Cheng K.-F. Org. Lett. 2001; 3: 1901
• 23 Ou J, Wong W.-T, Chiu P. Tetrahedron 2012; 68: 3450
• 24 Ou J, Wong W.-T, Chiu P. Org. Biomol. Chem. 2012; 10: 5971
• 25 Lam HW, Joensuu PM. Org. Lett. 2005; 7: 4225
• 26 Lam HW, Murray GJ, Firth JD. Org. Lett. 2005; 7: 5743
• 27 Deschamp J, Hermant T, Riant O. Tetrahedron 2012; 68: 3457
• 28 Deschamp J, Chuzel O, Hannedouche J, Riant O. Angew. Chem. Int. Ed. 2006; 45: 1292
• 29 Welle A, Diez-Gonzalez S, Tinant B, Nolan SP, Riant O. Org. Lett. 2006; 8: 6059
• 30 Du Y, Xu L.-W, Shimizu Y, Oisaki K, Kanai M, Shibasaki M. J. Am. Chem. Soc. 2008; 130: 16146
• 31 Li Z, Zhang Z, Yuan L, Jiang L, Li Z, Li Z. Synlett 2014; 25: 724
• 32 Representative Procedure Under an N₂ atmosphere, a dried Schlenk tube was charged with DPEphos (0.0094 g, 0.017 mmol, 3.5% equiv), [CuF(PPh₃)₃]·2MeOH (0.0141 g, 0.015 mmol, 3% equiv), and toluene (2 mL). Then the solution was stirred for 30 min, followed by addition of PMHS (0.06 mL) and additionally stirred for another 30 min. Solution of imine 1a (0.0912 g, 0.5 mmol) and dimethyl maleate 2a (0.080 mL, 0.64 mmol, 1.28 equiv) in toluene (1 mL) was added slowly to the flask, and the mixture was stirred until nearly complete consumption of 1a as monitored by TLC. Quenching of the reaction was conducted by the addition of ammonium fluoride solution in MeOH–H₂O (3:1; 10 mL, 1.5 mol/L) and stirred for 1 h. The mixture was filtered, the filtrate was separated, and the aqueous solution was extracted with CH₂Cl₂ (3 × 10 mL). The diastereomeric ratio (trans/cis = 81:19) was determined by GC analysis. Column chromatographic separation afforded the diastereomeric mixture of 3aa as colorless solid (0.144 g, 98% yield).
• 33 Stereomers were assigned by comparison the ¹H NMR coupling constants with literature data, see: Pohmakotr M, Yotapan N, Tuchinda P, Kuhakarn C, Reutrakul V. Tetrahedron 2007; 63: 4328
• 34 Chai Y, Hong S.-p, Lindsay HA, McFarland C, McIntosh MC. Tetrahedron 2002; 58: 2905
• 35 Bausch CC, Johnson JS. J. Org. Chem. 2008; 73: 1575