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 <i>anti</i> to the large substituent next to the nitrogen atom to provide the <i>cis</i>-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

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 <i>anti</i> to the large substituent next to the nitrogen atom to provide the <i>cis</i>-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

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 <i>anti</i> to the large substituent next to the nitrogen atom to provide the <i>cis</i>-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