Direct Asymmetric Mannich Reaction Catalyzed by a d-Glucosamine-Derived Organocatalyst

Abstract

Sugar-based primary amines have been employed as organocatalysts for the direct asymmetric Mannich reaction. By catalyst-screening experiments, we observed that catalysts bearing a hydroxy function at C-3 actively participated in the reaction, possibly through hydrogen bonding with the imine generated in situ, to provide β-amino carbonyl compounds with better diastereoselectivity and enantioselectivity. All the products were obtained in good to excellent enantiomeric excess.

Key words

aldimines - sugar amines - asymmetric catalysis - organocatalysis - amino carbonyl compounds - Mannich reaction

• References and Notes

• 1a Boons G.-J. Hale K. Organic Synthesis with Carbohydrates . Sheffield Academic Press; 2000
• 1b Carbohydrate Synthons in Natural Product Chemistry . Witczak ZJ. Tatsuta K. ACS Symposium Series 841; Washington: 2002
• 1c Bowen ML. Orvig C. Chem. Commun. 2008; 5077
• 1d Ernst B. Magnani JL. Nat. Rev. Drug Discov. 2009; 8: 661
• 1e Mastsuo I. Ito Y. US 7879766, 2011
• 2a Coll M. Pàmies O. Diéguez M. Adv. Synth. Catal. 2014; 356: 2293
• 2b Minuth T. Boysen MM. K. Beilstein J. Org. Chem. 2010; 6: 23
• 2c D’Onofrio A. Copey L. Jean-Gérard L. Goux-Henry C. Pilet G. Andrioletti B. Framery E. Org. Biomol. Chem. 2015; 13: 9029
• 2d Nishioka T. Shibata T. Kinoshita I. Organometallics 2007; 11: 1126
• 2e Benessere V. Lega M. Silipo A. Ruffo F. Tetrahedron 2011; 67: 4826
• 2f Mata Y. Claver C. Diéguez M. Pàmies O. Tetrahedron: Asymmetry 2006; 17: 3282
• 2g Shen C. Xia H. Zheng H. Zhang P. Chen X. Tetrahedron: Asymmetry 2010; 21: 1936
• 2h Goyard D. Telligmann SM. Goux-Henry C. Boysen MM. K. Framery E. Gueyrard D. Vidal S. Tetrahedron Lett. 2010; 51: 374
• 3a De Nisco M. Pedatella S. Bektaş S. Nucci A. Caputo R. Carbohydr. Res. 2012; 356: 273
• 3b Singh N. Pandey J. Tripathi RP. Catal. Commun. 2008; 9: 743
• 3c Shen C. Liao H. Shen F. Zhang P. Catal. Commun. 2013; 41: 106
• 3d Agarwal J. Peddinti RK. J. Org. Chem. 2011; 76: 3502
• 3e Otsuka Y. Sasaki A. Teshima T. Yamada K. Yamamoto T. Org. Lett. 2016; 18: 1338
• 3f Han X. Wang Y. Gai X. Zeng X. Synlett 2015; 2858
• 3g Agarwal J. Org. Biomol. Chem. 2016; 14: 10747
• 4a Agarwal J. Peddinti RK. Tetrahedron: Asymmetry 2010; 21: 1906
• 4b Shen C. Shen F. Xia H. Zhang P. Chen X. Tetrahedron: Asymmetry 2011; 22: 708
• 5 Liu K. Cui H.-F. Nie J. Dong K.-Y. Li X.-J. Ma J.-A. Org. Lett. 2007; 9: 923
• 6 Pu X.-W. Peng F.-Z. Zhang H.-B. Shao Z.-H. Tetrahedron 2010; 66: 3655
• 7 Emmerson DP. G. Hems P. Davis BG. Tetrahedron: Asymmetry 2005; 16: 213
• 8 Robak J. Kryczka B. Świerczyńska B. Zawisza A. Porwański S. Carbohydr. Res. 2015; 404: 83
• 9a Wouters AD. Trossini GH. G. Stefani HA. Lüdtke DS. Eur. J. Org. Chem. 2010; 2351
• 9b Appelt HR. Limberger JB. Weber M. Rodrigues OE. D. Oliveira JS. Lüdtke DS. Braga AL. Tetrahedron Lett. 2008; 49: 4956
• 9c Kong S. Fan W. Wu G. Miao Z. Angew. Chem. Int. Ed. 2012; 51: 8864
• 10a Puglisi A. Benaglia M. Raimondi L. Poletti L. Org. Biomol. Chem. 2011; 3295
• 10b Pinheiro DL. J. Batista GM. F. Gonçalves JR. Duarte TN. Amarante GW. Eur. J. Org. Chem. 2016; 459
• 10c Bauer T. Smoliński S. Appl. Catal. A. 2010; 375: 247
• 10d Shen C. Shen F. Zhou G. Xia H. Chen X. Liu X. Zhang P. Catal. Commun. 2012; 26: 6
• 10e Del Litto R. Benessere V. Ruffo F. Moberg C. Eur. J. Org. Chem. 2009; 1352
• 10f Ge X. Qian C. Chen Y. Chen X. Tetrahedron: Asymmetry 2014; 25: 596
• 10g Sawada D. Sasayama S. Takahashi H. Ikegami S. Tetrahedron 2008; 64: 8780
• 11a Bauer T. Tarasiuk J. Paśniczek K. Tetrahedron: Asymmetry 2002; 13: 77
• 11b Volkmann RA. In Comprehensive Organic Synthesis . Vol. 1, Chap. 1.12. Trost BM. Fleming I. Pergamon; Oxford: 1991. 355
• 11c Enders D. Reinhold U. Tetrahedron: Asymmetry 1997; 8: 1895
• 11d Bloch R. Chem. Rev. 1998; 98: 1407
• 11e Kobayashi S. Ishitani H. Chem. Rev. 1999; 99: 1069
• 12 Kobayashi S. Ueno M. In Comprehensive Asymmetric Catalysis . Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Berlin: 2004. Suppl. 1, Chap. 29.5 143
• 13 Agarwal J. Peddinti RK. Eur. J. Org. Chem. 2012; 6390
• 14 Zheng X. Qian Y.-B. Wang Y. Eur. J. Org. Chem. 2010; 515
• 15 Mannich Adducts 8a–n; General Procedure To a stirred solution of the appropriate benzaldehyde derivative 6 (0.2 mmol) and aniline derivative 7 (0.22 mmol) in dry CH₂Cl₂ were added, sequentially, cyclohexanone (5; 0.4 mmol), catalyst 1 (20 mol%), and BzOH (20 mol%). The resulting mixture was stirred at 20 °C for 48 h until the reaction was complete (TLC). The mixture was then concentrated, and the product was purified by column chromatography [silica gel, EtOAc–hexanes (10–25%)]. (2S)-2-[(S)-(4-Nitrophenyl)(phenylamino)methyl]cyclohexanone (8a) Reaction time: 48 h. Pale-yellow solid; yield: 50 mg (77%); mp 119–120 °C, [α]_D ²⁰ –62.7 (c = 0.20, CHCl₃). IR (KBr): 3360, 2926, 1698, 1599, 1513, 1344, 747, 693 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 8.14 (d, J = 8.5 Hz, 2 H), 7.56 (d, J = 8.5 Hz, 2 H), 7.08 (t, J = 7.5 Hz, 2 H), 6.71 (t, J = 7.0 Hz, 1 H), 6.54 (d, J = 7.0 Hz, 2 H), 4.86 (d, J = 4.0 Hz, 1 H), 2.93–2.83 (m, 1 H), 2.44 (d, J = 13.5 Hz, 1 H), 2.38–2.28 (m, 1 H), 2.15–2.05 (m, 2 H), 1.95–1.88 (m, 1 H), 1.70–1.55 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 210.6, 149.4, 147.0, 146.5, 129.1, 128.5, 123.6, 118.4, 114.0, 57.2, 56.1, 42.4, 29.0, 27.0, 24.9.
• 16a Gu Q. Jiang L.-X. Yuan K. Zhang L. Wu X.-Y. Synth. Commun. 2008; 38: 4198
• 16b Takech S. Kumagai N. Shibasaki M. Org. Lett. 2013; 15: 2632
• 16c Rachwalski M. Leenders T. Kaczmarczyk S. Kiełbasiński P. Leśniak S. Rutjes FP. J. T. Org. Biomol. Chem. 2013; 11: 4207