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%.