Total Synthesis of Sesquiterpenes via Intramolecular Ketene Cycloadditions: Isocomene and α-cis- and α-trans-Bergamotenes, an Approach to Seychellene

Article abstract of DOI:10.1021/jo00254a017

Cyclobutanone 2, a late intermediate in Wenkert's isocomene synthesis, was prepared by six-step sequence in 10percent overall yield.Carrol rearrangement of acetoacetate 9 gave ketone 10.Peterson olefination with ethyl (trimethylsilyl)propionate followed by hydrolysis gave acid 12 as a mixture of double bond position isomers.Addition of the corresponding acid chlorides 13 to Et3N in toluene at reflux gave cyclobutanone 4.Isomerization of the double bond of 4 with hydriodic acid gave 2.Isomerization of β-bergamotenes with hydriodic acid in benzene provided an effective route to the α-bergamotenes.Tricyclic ketone 28 was prepared by oxy-Cope rearrangement of allylic alcohol 27.Oxy-Cope rearrangement of propargylic alcohol 32 gave cyclooctadienone 33.Under some reaction conditions 33 was converted to cyclooctatrienolate 35, which was protonated to give 36 and underwent electrocyclic ring opening to give 38.