A three-carbon (n+1+2) ring expansion method for the synthesis of macrocyclic enones. Application to muscone synthesis.
The three-carbon ring expansion methodology commences with the preparation of a cyclic allene (C9, C11, C13), readily available from the corresponding cycloalkene via dibromocarbene addition and subsequent treatment with methyllithium. Dichloroketene addition to the cyclic allene regioselectively provides the [2+2] cycloadduct which is reductively dechlorinated with zinc in methanol. The resulting cyclobutanone is then catalytically hydrogenated; cyclobutanone ring opening is affected with trimethylsilyl iodide; immediate dehydroiodination of the resulting beta-iodocycloalkanone with diazabicycloundecane (DBU) provides the corresponding macrocyclic enone. The 15-membered enone was converted to dl,-muscone with (CH(3))(2)CuLi.
San Francisco State University, Department of Chemistry and Biochemistry, 1600 Holloway Avenue, San Francisco, CA 94132, USA.
Ihsan
I
Erden
Weiguo
W
Cao
Mary
M
Price
Michael
M
Colton