Stereochemie der Ringöffnung von Aziridinonen (α‐Lactamen)

Stereochemistry of Ring Opening of Aziridinones (α‐Lactams) The chiral, non‐racemic aziridinone ( R )‐ 4 (e.e. 92%) reacts with magnesium halides to afford the α‐halo amides ( S )‐ 3a (e.e. 88.8%), ( S )‐ 3b (e.e. 89.0%), and ( S )‐ 3c (e.e. 88.2%) in high yields. Acid‐catalysed hydrolysis of ( R )‐4 in aqueous acetone yields 74% of the α‐hydroxy amide ( S )‐3d (e.e. 88.0%). Methanolysis of ( R )‐ 4 in [D 4 ]methanol at 60°C followed the first‐order rate law with k = 1.53 ṁ 10 –5 s –1 yielding quantitatively a 82:18 mixture of the α‐methoxy amide ( S )‐ 3e (e.e. 89%) and the α‐amino ester ( R )‐ 14 (e.e. 87%). The latter is obtained exclusively (e.e. 87%) when ( R )‐ 4 reacts with sodium methoxide and methanol in ether while only the former is formed (e.e. 88.2%) by slow methanolysis in the presence of a catalytic amount of 4 ‐toluenesulfonic acid. The absolute configurations of the major enantiomers derived from ( R )‐ 4 are based on the retention on a Chirasil‐L‐Val capillary gas chromatography column, CD spectra, and the comparison with authentic samples of ( S )‐ 3a , obtained from ( S )‐ tert ‐leucine [( S )‐ 1 ] and ( S )‐ 3d . The results demonstrate that the N – C(3) bond of the aziridinone ( R )‐ 4 is cleaved by nucleophiles with a high degree of stereospecificity and inversion of configuration. This stereochemical course is at variance with that inferred from the methanolysis of the similar aziridinone ( R )‐ 7 . – Treatment of ( R )‐ 4 in [D 4 ]methanol with one equivalent of 3‐chloroperbenzoic acid ( 15 ) containing 5% of 3‐chlorobenzoic acid ( 16 ) affords carbon monoxide and the racemic oxaziridine 18 in quantitative yield, which is also obtained from the imine 19 in a very fast reaction. The acid 16 effects slow decomposition of ( R,S )‐ 4 into carbon monoxide and imine 19 , probably by general acid catalysis. The stereochemical result obtained from ( R )‐ 4 as well as the reaction conditions and differences in rate for formation and epoxidation of 19 suggest that in the peracid oxidation of an aziridinone the sequence of events consists of a rate‐limiting, acid‐catalysed decomposition into carbon monoxide and an imine, followed by very fast epoxidation of the latter. The previous mechanism, invoking as intermediates alleged aziridinone N ‐oxides, e.g. 17 , is not supported by the present study.