α-Chloronitroso compounds derived from carbohydrate ketones: cycloadditions with cyclic dienes, a synthesis of (–)-physoperuvine and a formal synthesis of (+)-epibatidine

Abstract

1,2-O-Isopropylidene-α-D-xylofuranose 9 was converted into 5-O-(tert-butyldiphenylsilyl)-3-chloro-3-deoxy-1,2-O-isopropylidene-3-C-nitroso-α-D-xylofuranose 17 in four steps, and a similar α-chloronitroso compound 8 was synthesised from 1,2∶5,6-di-O-isopropylidene-α-D-glucofuranose 6, the structures of 8 and 17 being confirmed by X-ray crystallography. Reaction of 8 or 17 with cyclohexa-1,3-diene in the presence of small amounts of water gave the cycloadduct (1S,4R)-3-aza-2-oxabicyclo[2.2.2]oct-5-ene, as its hydrochloride (–)-2, in ≥96% ee. Reactions of either 8 or 17 with cyclohepta-1,3-diene similarly gave (1R,5S)-7-aza-6-oxabicyclo[3.2.2]non-8-ene hydrochloride (–)-25 with ≥96% ee, but reactions with cyclopentadiene proceeded differently, with 17 giving the nitrone (E)-(3R,5R)-3-[5′-O-(tert-butyldiphenylsilyl)-3′-deoxy-1′,2′-O-isopropylidene-α-D-erythro-pentofuranos-3′-ylideneamino]-5-chlorocyclopentene N-oxide 19, the structure of which was determined by X-ray crystallography. The dihydrooxazines (–)-25 and (–)-2 were used in syntheses of (–)-physoperuvine (–)-34 and (+)-epibatidine (+)-40, respectively. A pseudoenantiomeric α-chloronitroso compound 51 was also prepared from 2,3-O-isopropylidene-α-L-sorbofuranose 44, and reaction of 51 with cyclohexa-1,3-diene gave (+)-2 with 97% ee.