Vanadium(<scp>II</scp>)‐ and Niobium(<scp>III</scp>)‐Induced, Diastereoselective Pinacol Coupling of Peptide Aldehydes to Give a <i>C</i>₂‐Symmetrical HIV Protease Inhibitor

Abstract

Abstract Peptide aldehydes 15 a–c are prepared without epimerization from enantiomerically pure ( S )‐α‐amino acids (Scheme 3). Reductive pinacol homocoupling of 15 a–c , induced by vanadium complex 11 or niobium complex 16 in refluxing THF, yields C 2 ‐symmetrical ( S,R,R,S )‐configurated 6a , 6b and 2 , respectively, with moderate to high stereoselectivity (Scheme 4). In a novel protocol for the preparation and utilization of THF solutions of 11 , the isolation of air‐sensitive intermediates can be avoided and the potent HIV protease inhibitor 2 prepared in enantio‐ and diastereomerically pure form on a kilogram scale without chromatographic purification. The ( S,R,R,S ) selectivity of the pinacol homocouplings is confirmed by means of an independent, stereochemically unequivocal synthesis of 6 a and 2 from D ‐mannitol 4 (Scheme 1).