Pd-catalyzed cross-coupling of allylsilane-vinylcopper species with aryl and vinyl halides: the first total synthesis of (−)-nomadone

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The reaction of allene with a lower order silylcuprate 3 leads to an allylsilane-vinylcopper intermediate 4, which undergoes palladium-catalyzed cross-coupling reaction with both vinyl and aryl halides. The influence of several factors such as the nature of the transition metal used as catalyst, the temperature of the reaction, and the order of addition are studied. This simple methodology allows the synthesis in one step of isoprenylsilanes, which can be conveniently coupled with different isoprenic aldehydes to give several acyclic natural terpenes. Thus, we were able to synthesize, in two steps from allene, the natural monoterpenes (±)-ipsdienol and (±)-ipsenol, which are the principal components of the aggregation pheromone of the bark beetle Ips paraconfusus. On the other hand, the allyl-terminated reaction of isoprenylsilane 7 with the natural monoterpene ( S)-citronellal leads to an intermediate, which is readily converted into the natural sesquiterpene (−)-Nomadone in two almost quantitative steps. The nomadone sesquiterpene is a component of the cephalic gland's secretion of Nomada bees. As far as we know this is the first reported total synthesis of (−)-nomadone.