Enantiomerically pure 3-Oxa-2.7-diazabicyclo[3.3.0]octanes: Preparation, analysis of conformation and test for enantioselective catalysis

Abstract

Amino alcohols 5 were prepared by various methods starting from (S)-(+)-alanine and (S)-(+)-valine. Swern oxidation of S afforded aldehydes 6 which were treated without isolation with N-alkylhydroxylamines to give nitrones 7A, B. These underwent spontaneously an intramolecular cycloaddition yielding 3-oxa-2.7-diazabicyclo[3.3.0]octanes 9A, B. The oximes 8C obtained by reaction of 6 with hydroxylamine were converted to compounds 9C in toluene at 110°C. Products 9 were obtained enantiomerically pure. X-ray analyses were performed with 9Ac and Bc. The NMR coupling constants of 9Ac and Bc are in good agreement with those calculated from the torsional angles detected by the X-ray analyses. Thus, their conformation in solution resembles the conformation in the crystalline state. The majority of compounds 9 exists in a similar conformation as the NMR data indicate. On the other hand, substituent: at position 4 or 5 in compounds 9 give rise to an inversion of conformation. In compounds 10 and 11 two 3-oxa-2.7-diazabicyclo[3.3.0]octane units are connected by an ethylene bridge. Reduction of compounds 9 yielded pyrrolidines 12. 2.7-Diazabicyclo[3.3.0]octane 14 was obtained via 13 by reduction starting from 9Ag. Compounds 9-12 and 14 were tested as catalysts for the reaction of diethylzinc with benzaldehyde. This reaction was catalyzed effectively by all compounds, however, the enantiomeric excesses did not exceed 61%. © 1995 Elsevier Science Ltd.