Cembranolides. total synthesis

Marshall, J.A., and DeHoff. B.S.. Cembranolide total synthesis. Anisomelic acid, Tetrahedron, 43, 4849, 1987. 

The reaction was also applied in a more complicated case during the total synthesis of the cembranolide ( )-anisomelic acid74. 

Other applications of this method include, e.g. the synthesis of the antibiotic A26771B (5i) [118] and the marine cembranolide isolobophytolide [119], Trost and Warner [120] reported that a-sulfonyl sulfones can also serve as the substrates of ir-allylpalladium complexes for macrocyclization. Furthermore, an a-hydroxy-carbonyl ketone was alkylated intramolecularly by a a-allylpalladium complex in the total synthesis of the macrocyclic sesquiterpene humulene [121]. 

The first asymmetric total synthesis of ( )-trany-cembranolide (295) was reported by Taber and Song in 1997 (Scheme 6-39). The key step in the synthesis is the diastereoselective Rh-mediated cyclization of the enantiomerically pure diazo ester 288 to the tetrahydrofuran 289. 

Marshall, (.A. and Andrews, R.C. (1986) Stereoselective total synthesis of ( )-isolobophytolide, a marine cembranolide natural product Tetrahedron Lett., 27, 5197-5200. 

Marshall, J.A., Andrews, R.C., and Lebioda, L. (1987) Synthetic studies on cembranolides stereoselective total synthesis of isolobophytolide. J. Org. Chem., 52, 2378-2388. 

Marshall, (.A. and Gung, W.Y (1988) Stereoselective total synthesis of cembranolides through cydization of a homochiral (a-alkoxyallyl) stannane precursor. Tetrahedron Lett., 29, 3899-3902. 

Nishitani, K., Konomi, T, Mimaki, Y, Tsimoda, T, and Yamakawa, K. (1993) Total synthesis of ( )-cembranolide via Cr(ll) mediated intramolecular macrocydization of p-alkoxycarbonylallyl halide. Heterocydes, 36,1957-1960. 

Other applications of carbanions a to a sulfone in total syntheses have recently been reported. Most of them used allylic sulfones or allylic halides. Two examples are reported here. In the synthesis of a precursor of cembranolides, a sulfone derived from geranyl bromide was coupled with an allylic alcohol epoxide (Scheme 65). An interesting point was that the coupling reaction gave high yields only when the lithiated sulfone was allowed to react with the epoxymagnesio alkoxide (the lithium salt of the epoxy alcohol did not react at all with the lithiated sulfone). 

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