β-Aminosulfonamide-Catalyzed Direct Asymmetric Aldol Reaction in Brine

Abstract

Direct asymmetric aldol reactions of aldehydes with ketones in the presence of a catalytic amount of β-aminosulfonamide 2 and trifluoroacetic acid in brine results in the formation of the corresponding anti-aldol products in high yields with up to 96% enantiomeric excess. The anti-aldol products obtained by using organocatalyst 2 have the opposite absolute configuration to those obtained using the similar sulfonamide catalyst 1, which was reported previously by us.

Key words

organocatalyst - aldol reaction - sulfonamide - brine - asymmetric

References and Notes

• For selected reviews on organocatalysis, see:
• 1a Dalko PI. Moisan L. Angew. Chem. Int. Ed.  2004,  43:  5138 
• 1b Pellissier H. Tetrahedron  2007,  63:  9267 
• 1c Mukherjee S. Yang JW. Hoffmann S. List B. Chem. Rev.  2007,  107:  5471 
• 1d Dondoni A. Massi A. Angew. Chem. Int. Ed.  2008,  47:  4638 
• 1e Lattanzi A. Chem. Commun.  2009,  1452 
• 1f Liu X. Lin L. Feng X. Chem. Commun.  2009,  6145 
• 2 Modern Aldol Reactions   Vol. 1 and 2:  Mahrwald R. Wiley-VCH; Weinheim: 2004. 
• For selected reviews on organocatalysis in water, see:
• 3a Gruttadauria M. Giacalone F. Noto R. Adv. Synth. Catal.  2009,  351:  33 
• 3b Paradowska J. Stodulski M. Mlynarski J. Angew. Chem. Int. Ed.  2009,  48:  4288 
• 3c Raj M. Singh K. Chem. Commun.  2009,  6687 
• For selected recent examples of organocatalyzed aldol reactions in water, see:
• 3d An Y.-J. Zhang Y.-X. Wu Y. Liu Z.-M. Pi C. Tao J.-C. Tetrahedron: Asymmetry  2010,  21:  688 
• 3e Zhang S.-P. Fu X.-K. Fu S.-D. Tetrahedron Lett.  2009,  50:  1173 
• 3f Zhou H. Xie Y. Ren L. Wang K. Adv. Synth. Catal.  2009,  351:  1284 
• 3g Ma X. Da C S. Yi L. Jia Y.-N. Guo Q.-P. Che L.-P. Wu F.-C. Wang J.-R. Li W.-P. Tetrahedron: Asymmetry  2009,  20:  1419 
• 3h Chimni SS. Singh S. Kumar A. Tetrahedron: Asymmetry  2009,  20:  1722 
• 3i Fu S.-D. Fu X.-K. Zhang S.-P. Zou X.-C. Wu X.-J. Tetrahedron: Asymmetry  2009,  20:  2390 
• 3j Vishnumaya MR. Singh VK. J. Org. Chem.  2009,  74:  4289 
• 3k Nisco MD. Pedatella S. Ullah H. Zaidi JH. Naviglio D. Ozdamar O. Caputo R. J. Org. Chem.  2009,  74:  9562 
• 3l Vishnumaya MR. Singh VK. J. Org. Chem.  2009,  74:  4289 
• 3m Mase N. Noshiro N. Mokuya A. Takabe K. Adv. Synth. Catal.  2009,  351:  2791 
• 3n Tea Y.-C. Lee PP. Synth. Commun.  2009,  39:  3081 
• 3o Jia Y.-N. Wu F.-C. Ma X. Zhu G.-J. Da C S. Tetrahedron Lett.  2009,  50:  3059 
• 3p Ramasastry SSV. Albertshofer K. Utsumi N. Barbas CF. Org. Lett.  2008,  10:  1621 
• 3q Zhu M.-K. Xu X.-Y. Gong L.-Z. Adv. Synth. Catal.  2008,  350:  1390 
• 3r Zu L. Xie H. Li H. Wang J. Wang W. Org. Lett.  2008,  10:  1211 
• 3s Gandhi S. Singh VK. J. Org. Chem.  2008,  73:  9411 
• 3t Zhao J.-F. He L. Jiang J. Tang Z. Cun L.-F. Gong L.-Z. Tetrahedron Lett.  2008,  49:  3372 
• 3u Huang W.-P. Chen J.-R. Li X.-Y. Cao Y.-J. Xiao W.-J. Can. J. Chem.  2007,  85:  208 
• 3v Huang J. Zhang X. Armstrong DW. Angew. Chem. Int. Ed.  2007,  46:  9073 
• 3w Gryko D. Saletra WJ. Org. Biomol. Chem.  2007,  5:  2148 
• 3x Hayashi Y. Sumiya T. Takahashi J. Gotoh H. Urushima T. Shoji M. Angew. Chem. Int. Ed.  2006,  45:  958 
• 3y Mase N. Nakai Y. Ohara N. Yoda H. Takabe K. Tanaka F. Barbas CF. J. Am. Chem. Soc.  2006,  128:  734 
• 4 Nakayama K. Maruoka K. J. Am. Chem. Soc.  2008,  130:  17666 
• 5 Miura T. Yasaku Y. Koyata N. Murakami Y. Imai N. Tetrahedron Lett.  2009,  50:  2632 
• 6 Miura T. Imai K. Ina M. Tada N. Imai N. Itoh A. Org. Lett.  2010,  12:  1620 
• 7 Imai N. Nokami J. Nomura T. Ninomiya Y. Shinobe A. Matsushiro S. Bull. Okayama Univ. Sci.  2002,  47 
• 9a Bassan A. Zou W. Reues E. Himo F. Córdova A. Angew. Chem. Int. Ed.  2005,  44:  7028 
• 9b Dziedzic P. Zou W. Háfren J. Córdova A. Org. Biomol. Chem.  2006,  4:  38 
• 10 Mase N. Watanabe K. Yoda H. Takabe K. Tanaka F. Barbas CF. J. Am. Chem. Soc.  2006,  128:  4966 
• 11 We assume that the aldol reactions are accelerated by the use of brine (salting-out effect),^¹0 see: Maya V. Singh VK. Org. Lett.  2007,  9:  1117 

8

A typical procedure for the aldol condensation using 2 and 6a is as follows: To a colorless suspension of p-nitro-benzaldehyde (6a; 90.7 mg, 0.600 mmol) and the organo-catalyst 2 (33.9 mg, 0.120 mmol) in brine (1.2 mL), were added cyclohexanone (0.62 mL, 6.00 mmol) and TFA (2.2 µL, 0.030 mmol) at r.t. The reaction mixture was stirred at r.t. for 36 h, and extracted three times with EtOAc. The organic layers were combined, washed with brine, dried over anhydrous MgSO₄, and evaporated. The residue was purified by flash column chromatography on silica gel (toluene-EtOAc, 4:1) to afford pure 8a (121.3 mg, 81%) as a colorless solid.