A New General Approach to Enantiomerically Pure Cyclic and Open‐Chain (<i>R</i>)‐ and (<i>S</i>)‐α,α‐Disubstituted α‐Amino Acids

Abstract

Abstract A wide range of cyclic and open‐chain α,α‐disubstituted α‐amino acids 1a‐p were prepared. The racemic N ‐acylated α,α‐disubstituted amino acids were resolved by coupling to chiral amines 15‐18 derived from ( S )‐phenylalanine to form diastereoisomers 19/20 or 21/22 that could be separated by crystallization and/or flash chromatography on silica gel ( Scheme 3 ). Selective cleavage via the 1,3‐oxazol‐5(4 H )‐ones 10a‐p gave the corresponding optically pure α,α‐disubstituted amino‐acid derivatives 11 or 12 in high yield ( Scheme 3 ). The absolute configurations of the α,α‐disubstituted amino acids were determined from X‐ray structures of the diastereoisomers 20, 21g′, 22d .