Nucleophilic ring-opening of trans and cis aziridino alcohols 1 (1') and 2 (2') by hydride-and by methyl-transfer reagents has been studied. In general, good to excellent C-2 selectivity was observed (the regioselectivity being betterfor the trans isomers) and the results can be interpreted in terms of directive effects exerted by the C-l hydroxyl group. However, complete C-3 selectivity was observed in the reactions of 1 and 2 with AlMe,, indicating a complexation effect of the C-4 benzyloxy group in those cases.
We have previously described methods for the preparation of optically pure aziridino alcohols, and have used these compounds as starting materials for the enantioselective synthesis of p-lactam antibiotics1s2. Key steps in our routes to (+)-thienamycin and (+)-PS-5 were thus regioselective ring-openings of suitable aziridino alcohols by hydride-l and alkyl-transfer2 reagents, respectively. In this paper, we present the results of a more systematic investigation of the regioselectivity of such ring-opening reactions.
The substrates chosen were the trans and cis aziridino alcohols 1 (I') and 2 (2') which provide variations in both aziridine ring stereochemistry and in the' steric/electronic effects of the C-4 substituents. The N-tosyl protective group activates the aziridme ring towards nucleophilic attack, and also offers advantages in subsequent p-lactam ring-closure 2. The substrates used in the present study were racemic, but materials of high enamiomeric purity are readily available from Sharpless-type epoxides as demonstrated previously1s2 and in the following papes. As in our preliminary study', the hydride-transfer reagents chosen were Red-Al, DIBAL, and LiAlH,, while organocupmtes2 and trimethylaluminium reagents were used to introduce alkyl groups.