Enantiospecific synthesis of (+)-retronecine, (+)-crotonecine, and related alkaloids

Reaction of 2,3-O-isopropylidene-D-ribose (8) with diallylzinc gave a triol, which on treatment with periodate was converted into 5,6,7-trideoxy-2,3- O-isopropylidene-L-ribo-hept-6-enofuranose (10) (86%). Reaction with hydroxylamine hydrochloride in pyridine gave an oxime (11), which was treated with methanesulphonyl chloride in pyridine to yield 5,6,7-trideoxy-2,3-O- isopropylidene-4-O-methylsulphonyl-L-ribo-hept-6-enononitrile (12) (87% overall). Reduction with lithium aluminium hydride and cyclisation followed by treatment with benzyl chloroformate gave (2R,3S,4R)-2-allyl-1-benzyloxycarbonyl- 3,4-isopropylidenedioxypyrrolidine (14), which on oxidation and subsequent reaction with diazomethane yielded (2R,3S,4R)-methyl (1-benzyloxycarbonyl-3,4- isopropylidenedioxypyrrolidin-2-yl)acetate (15b) (35%). A higher-yielding route to diester (15b) proceeded from 2,3-O-isopropylidene-D-erythrose (17), which was converted via its oxime into 2,3-O-isopropylidene-4-O-methylsulphonyl-D- erythrononitrile (19) (91%). Reaction with methyl bromoacetate and activated zinc, followed by base-catalysed cyclisation, gave (3S,4R)-methyl (3,4-isopropylidenedioxypyrrolidin-2-ylidene)acetate (21) (78%), which with cyanoborohydride followed by N-acylation produced compound (15b) (87%). Treatment of diester (15b) with acid produced a ?-lactone (23), which was deoxygenated via its O-thiocarbonylimidazolide (24). Hydrogenolysis yielded (1R,5R)-2-oxa-6-azabicyclo[3.3.0]octan-3-one hydrochloride (6) (69% overall), which can be converted by known methods into (+)-retronecine (5) and other pyrrolizidine alkaloids. (1S,5R,8R)-Ethyl 8-hydroxy-3-oxo-2-oxa-6-azabicyclo[3. 3.0]octane-6-carboxylate (28) was converted into its silyl ether (29), which underwent Dieckmann cyclisation to the pyrrolizidine (31), which is convertible by known methods into (+)-crotanecine (7).