DOI: 10.1021/jo101735u Published on Web 11/11/2010 J. Org. Chem. 2010, 75, 8457–8464 8457 r 2010 American Chemical Society pubs.acs.org/joc Chemistry of 2-Nitroglycals: A One-Pot Three-Component Stereoselective Approach toward 2-C-Branched O-Galactosides Pavan K. Kancharla and Yashwant D. Vankar* Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India vankar@iitk.ac.in Received September 5, 2010 A convenient one-pot three-component approach for the synthesis of 2-C-branched O-glycosides has been developed from 2-nitroglycals. These 2-C-branched sugars have been shown to be precursors for a variety of biologically and synthetically relevant molecules. Introduction 2-Nitroglycals are versatile intermediates for the stereo- selective synthesis of various glycosides. 1 Besides being good Michael acceptors, they also permit (2 þ 3) and (2 þ 4) cycloadditions, thus permitting the preparation of a number of other useful carbohydrate derived synthons. Optimized conditions have been developed for the stereoselective addi- tion of a variety of nucleophiles to the 2-nitroglycals, result- ing in the synthesis of several O-glycosides, 2 thioglycosides, 3 glycophosphonates, 4 C-glycosides, 5 and N-glycosides (for the synthesis of nucleosides). 6 Further, the nitro functionality is of enormous importance in organic synthesis, particularly as it can readily be converted into an amino or a hydroxyl- amino 7 group. Also, the nitro groups allow the generation of a reactive radical in the presence of n-Bu 3 SnH-AIBN 8 that could be exploited further. As a result, 2-nitroglycals serve as useful intermediates in the synthesis of 2-deoxy-2-amino glycosides, which are constituents of several nucleoside and aminoglycosidic antibiotics. 9 The base-catalyzed 2-nitrogly- cal concatenation is extensively studied and has also been applied in the synthesis of mucins, 10a a family of highly O-glycosylated glycoproteins that play an important role in various biological processes. 10b,c (1) (a) Schmidt, R. R.; Vankar, Y. D. Acc. Chem. Res. 2008, 41, 1059. (b) Xue, W.; Sun, J.; Yu, B. J. Org. Chem. 2009, 74, 5079. (c) Zhang, Q.; Sun, J.; Zhang, F.; Yu, B. Eur. J. Org. Chem. 2010, 3579. (2) (a) Holzapfel, C. W.; Marais, C. F.; van Dyk, M. S. Synth. Commun. 1988, 18, 97. (b) Das, J.; Schmidt, R. R. Eur. J. Org. Chem. 1998, 1609. (3) Barroca, N.; Schmidt, R. R. Org. Lett. 2004, 6, 1551. (4) Pachamuthu, K.; Figueroa-Perez, I.; Ali, I.; Schmidt, R. R. Eur. J. Org. Chem. 2004, 3959. (5) (a) Pachamuthu, K.; Gupta, A.; Das, J.; Schmidt, R. R.; Vankar, Y. D. Eur. J. Org. Chem. 2002, 9, 1479. (b) Gopal Reddy, B.; Vankar, Y. D. Angew. Chem., Int. Ed. 2005, 44, 2001. (c) Zhang, T; Yu, C.-Y.; Huang, Z.-T.; Jia, Y.-M. Synlett 2010, 14, 2174. (6) Winterfeld, G. A.; Das, J.; Schmidt, R. R. Eur. J. Org. Chem. 2000, 3047. (7) Larock, R. C. Comprehensive Organic Transformations, 2nd ed.; John Wiley and Sons, Inc.: New York, 1999. (8) (a) Ono, N.; Miyake, H.; Kamimura, A. Tetrahedron 1985, 41, 4013. (b) Bowman, W. R.; Crosby, D.; Westlake, P. J. J. Chem. Soc., Perkin Trans. 1 1991, 73. (9) Haddad, J.; Kotra, L.; Mobashery, S. Aminoglycoside Antibiotics: Structures and Mechanisms of Action. In Glycochemistry Principles, Synthe- sis and Applications; Wang, P. G., Bertozzi, C. R., Eds.; Marcel Dekker: New York, 2001; p 307. (10) (a) Geiger, J.; Reddy, B. G.; Winterfeld, G. A.; Weber, R.; Przbylski, M.; Schmidt, R. R. J. Org. Chem. 2007, 72, 4367. (b) Devine, P. L.; McKenzie, I. F. C. Bioessays 1992, 14, 619. (c) Varki, A. Glycobiology 1993, 3, 97.