Approach to Monobactams and Nocardicins via Diastereoselective Kinugasa Reaction

A Kinugasa
reaction between copper­(I) acetylides and cyclic nitrones
derived from chiral amino alcohols and glyoxylic acid is reported.
The stereochemical preferences observed in this reaction are discussed.
The alkyne molecule approaches the nitrone exclusively anti to the large substituent next to the nitrogen atom to provide the cis-substituted β-lactam ring preferentially. The
six-membered oxazinone ring can be opened by reduction with lithium
borohydride. Deprotection of the β-lactam nitrogen atom can
be achieved by lithium in liquid ammonia reduction or by CAN oxidation,
depending on the substituents attached to the four-membered azetidinone
ring. The adducts obtained by the Kinugasa reaction provide an attractive
entry to a variety of monocyclic β-lactam structures related
to monobactams and nocardicins.