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 features a benzannulation reaction of a Fischer carbene complex in the assembly of the tricyclic core of the molecule containing the acyclic carbohydrate side chain and the phenol functions differentiated. In this work, a synthesis 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 alkyne begins with the exclusively syn selective Mukaiyama aldol reaction of 2-trimethylsiloxyfuran with the 2S,3R-dihydroxybutanal protected as its acetonide. Conjugate addition of a vinyl cuprate to the butenolide obtained from this reaction gives a single stereoisomer of an intermediate that has all of the chiral centers of the acyclic carbohydrate side chain. The final carbon in the alkyne is introduced by a Corey-Fuchs reaction which is used to 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 alkyne 45 and carbene complex 44 which demonstrates the viability of a synthetic strategy that employs the reaction of an aryl Fischer carbene complex with a complex alkyne containing the functionality needed for the synthesis of olivin. (C) 1999 Elsevier Science Ltd. All rights reserved.