Development and applications of amino acid derived organometallics

This Account describes the discovery and development of a family of organometallic reagents derived from naturally occurring alpha-amino acids that have found widespread use in the stereocontrolled synthesis of non-natural analogues of proteinogenic amino acids. The general approach that we have taken involves the conversion of the side chain of enantiomerically pure naturally occurring, amino acids, such as serine, aspartic acid and glutamic acid, into the corresponding primary alkyl iodide, followed by conversion into the corresponding organozinc reagents. Subsequent palladium- or copper-catalysed reactions of these reagents allow the synthesis of a wide variety of functionalised alpha-, beta- and gamma-amino acid derivatives, without loss of stereochemical integrity. Insights gained from spectroscopic and kinetic studies into the stability of functionalised organozinc reagents are included.