Preparation of pure enantiomeric 3-oxa-2,7-diazabicyclo[3.3.0]octanes and their conversion to other bicyclic ring-systems

Pure Enantiomeric (S)-N-benzylalaninol (R-1 = Me) and (S)-N-benzylvalinol ( R-1 = i-Pr) were allylated with Br-CH2-CH=(CRR3)-R-2 (R-2 = R-3 = H; R-2 = Ph, R-3 = H; R-2 = R-3 = Ph). Swern oxidation followed by treatment with me thylhydroxylamine afforded nitrones 6 (Me-N(O)=CH-CHR1-N(CH2Ph)CH2-CH=(CRR3 )-R-2) which underwent an intramolecular 1,3-dipolar cycloaddition providin g 3-oxa-2,7-diazabicyclo[3.3.0]octanes, e. g. (1R,5R,8S)-7-benzyl-2,8-dimet hyl-3-oxa-2,7-diazabicyclo[3.3.0]octane 7a (R-1 = Me, R-2 = R-3 = H) and (1 R,4R,5R,8S)-7-benzyl-2,8-dimethyl-4-phenyl-3-oxa-2,7-[3.3.0]-octane 7b (R-1 = Me, R-2 = Ph, R-3 = H). Reductive ring opening of 7a and 7b afforded the corresponding alpha-hydrox yalkylated pyrrolidines (9a: R-2 = H or 9b: R-2 = Ph, resp.). Condensation of these compounds with benzaldehyde yielded a mixture of diastereomeric 4- oxa-2,8-diazabicycla[4.3.0]-nonanes: 10a/11a (1R,3S,6R,9S)/(1R,3R,6R,9S) R- 1 = Me, R-2 = Ph, R-3 = H and 10b /11b (1R,3S,5R,6R,9S)/(1R,3R,5R,6R,9S) R- 1 = Me, R-2 = Ph, R-3 = H. Pyrrolidine 9b was converted to the mesylate whi ch formed (1R,4S,5R,7S)-3-benzyl-4,6-dimethyl-7-phenyl-3,6-diazabicyclo[3.2 .0]heptane 13 along with (4R,5S)-1-benzyl-3,5-dimethyl-4-styryl-imidazolidi ne 15 upon treatment with sodium hydroxide.