Enantioselective process for synthesis of (+)- petromyroxol and its diastereomers

A process for synthesis of (+)-petromyroxol or diastereomers thereof, comprising the steps of:

• a) subjecting the epoxide (3aR,5R,6aR)-2,2-dimethyl-5-((R)-oxiran-2-yl)tetrahydrofuro[2,3-d][1,3]dioxole to ring opening in the presence of n-BuLi to afford alcohol (S)-1-((3aR,5R,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)hexan-1-ol;
• b) benzylating the free —OH group of the alcohol of step (a) in the presence of NaH and benzyl bromide in THF to afford benzylether (3aR,5R,6aR)-5-((S)-1-(benzyloxy)hexyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole;
• c) subjecting the benzylether of step (b) to C-allylation with allyltrimethylsilane in the presence of BF3·Et2O in dichloromethane to afford a mixture of α- and β-C-allylglycosides (2R,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol-α and (2S,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol-β;
• d) subjecting one or the other allylglycosides of step (c) to acetylation to afford the corresponding acetate of (2R,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol-α or (2S,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol-β;
• or
• e) subjecting the (2R,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol-α or (2S,3R,5R)-2-allyl-5-((S)-1-(benzyloxy)hexyl)tetrahydrofuran-3-ol-β of step (c) to a Mitsunobu reaction in the presence of p-nitrobenzoic acid, diisopropylazodicarboxylate, and triphenylphosphine in dichloromethane to afford the corresponding benzoate;
• f) subjecting a benzoate of step (e) or acetate of step (d) to oxidative olefin cleavage in the presence of OsO4 and NaIO4 to afford an intermediate aldehyde, followed by two-carbon Wittig homologation of said aldehyde to afford a corresponding unsaturated ester;
• g) hydrogenating the unsaturated ester of step (f) to afford the corresponding saturated ester;
• and
• h) subjecting the saturated ester of step (g) to saponification using base in solvent to afford (+)-petromyroxol or diastereomers thereof.