Synthesis of C-Protected α-Amino Aldehydes of High Enantiomeric Excess from Highly Epimerizable N-Protected α-Amino Aldehydes

A new procedure for the preparation of C-protected alpha-amino aldehydes of high enantiomeric excess is illustrated using five differently substituted alpha-(N-Fmoc)amino aldehydes as starting materials. Highly epimerization-prone substrates were converted to the corresponding morpholino nitrile-protected alpha-amino aldehydes with minimal racemization (products >/= 89% ee). Morpholino nitrile derivatives of phenylglycinal were crystallized and subjected to X-ray structural analysis, allowing for definitive determination of the stereochemistry of amino nitrile formation. A rationale for the stereoselectivity of amino nitrile formation is presented.