Stereochemie der Ringöffnung von Aziridinonen (α‐Lactamen)

Abstract

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 [D4]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 [D4]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.