Enantioselective Friedel-Crafts Alkylation of Indoles with Nitroalkenes

Significance

Friedel-Crafts alkylation with trans-β-nitrostyrene afforded product 4 in excellent yield and enantioselectivity. Although 5 mol% was considered optimal, using 1 mol% catalyst gave satisfactory yields and enantioselectivities (94%, 90% ee). The bifunctional tridentate bis(oxazoline) ligand 3 sets a new standard for indoles bearing an N-methyl substituent, as enantio­selectivity was enhanced by 40% compared with previous reports. Also, the reaction could be easily extended to aliphatic nitroalkenes with neither a reduction in reaction rate nor in enantioselectivity. This is the first system that works equally well with aromatic, heteroaromatic, and aliphatic nitroalkenes (previous related report: Y.-X. Jia et al. J. Org. Chem. 2006, 71, 75-80). Ortho-substitution on the aromatic moiety of nitrostyrenes lowered the ee value regardless of electronic effects.