Pyrrole-Protected β-Aminoalkylzinc Reagents for the Enantioselective Synthesis of Amino-Derivatives

Abstract

Chiral beta-aminoalkylzinc halides were prepared starting from optically pure commercial beta-amino-alcohols. These amino-alcohols were converted to the correspondingN-pyrrolyl-protected alkyl iodides which undergo a zinc insertion in the presence of LiCl (THF, 25 degrees C, 10-90 min). Subsequent Negishi cross-coupling or acylation reactions with acid chlorides produced amino-derivatives with retention of chirality. Diastereoselective CBS-reductions of some preparedN-pyrrolyl-ketones provided 1,3-subsitutedN-pyrrolyl-alcohols with high diastereoselectivity. Additionally, a deprotection procedure involving an ozonolysis allowed the conversion of the pyrrole-ring into a formamide without loss of optical purity.