The Combination of Diallylboration and Ring-Closing Metathesis in the Synthesis of Spiro-β-Amino Alcohols and (±)-Cephalotaxine

A convenient and practical methodology for the preparation of various spiro-beta-amino alcohols has been elaborated. The approach involves allylboration and ring-closing methathesis to prepare spirobicyclic compounds and their subsequent modification to spiro-beta-amino alcohols containing four- to six-membered azacycles. N-Boc-protected azaspirocyclic olefins reacted with NBS in solvent under reflux to give tricyclic bromocyclocarbamates. The structure of one of the bromides was established by single-crystal X-ray analysis. The dehydrobromination of the tricyclic bromides with tBuOK produced olefins in good yields, which underwent allylic-type rearrangement in the presence of MgBr2 center dot Et2O. Alkaline hydrolysis of the rearranged carbamates led to diastereomerically pure spiro-beta-amino alcohols. The structure of the dimethyl-substituted amino alcohol was proved by single-crystal X-ray analysis. rac-(5R*,6S*)-1-Azaspiro vertical bar 4.4 vertical bar non-7-en-6-ol was used in the formal synthesis of cephalotaxine. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)