Asymmetric electrophilic functionalization of amino-substituted heteroaromatic compounds: a convenient tool for the enantioselective synthesis of nitrogen heterocycles.

Abstract

The catalytic asymmetric electrophilic functionalization of the less reactive N-heteroaromatic compounds has been reported using the approach of the introduction of an exocyclic amino substituent. This strategy has allowed the enantioselective Friedel-Crafts alkylation in pyrazoles, isoxazoles or isothiazoles, as well as in aminoindoles, aminobenzofurans and aminobenzothiophenes. Several stereoselective methods have been used for the 1,4-addition or 1,2-addition of these heteroaromatic compounds to different electrophiles emploing organocatalysts or chiral metal complexes. The presence of the activating exocyclic amino subtituent has been used as well as nucleophile for tandem reactions describing formal cycloadditions ([3+2] and [3+3]) for the synthesis of highly funtionalized chiral nitrogen heterocycles.