Synthetic studies towards the total synthesis of olivin: Synthesis of a fully functionalized alkyne appropriate for the benzannulation reaction

A synthetic strategy for the synthesis of olivin has been developed which f eatures a benzannulation reaction of a Fischer carbene complex in the assem bly of the tricyclic core of the molecule containing the acyclic carbohydra te side chain and the phenol functions differentiated. In this work, a synt hesis of a key alkyne is developed to be used in a benzannulation reaction that constructs the B-ring of olivin. This alkyne incorporates four of the five asymmetric centers in the aglycone of olivin. The synthesis of this al kyne begins with the exclusively syn selective Mukaiyama aldol reaction of 2-trimethylsiloxyfuran with the 2S,3R-dihydroxybutanal protected as its ace tonide. Conjugate addition of a vinyl cuprate to the butenolide obtained fr om this reaction gives a single stereoisomer of an intermediate that has al l of the chiral centers of the acyclic carbohydrate side chain. The final c arbon in the alkyne is introduced by a Corey-Fuchs reaction which is used t o install the alkyne function. The synthesis of the alkyne is accomplished in 15 steps (6 % overall yield) and can provide gram quantities of material . Initial evaluation of the key benzannulation step was performed with alky ne 45 and carbene complex 44 which demonstrates the viability of a syntheti c strategy that employs the reaction of an aryl Fischer carbene complex wit h a complex alkyne containing the functionality needed for the synthesis of olivin. (C) 1999 Elsevier Science Ltd. All rights reserved.