The stereocontrolled synthesis of the water mold hormone (Z)-24(28)-dehydro-oogoniol and the Luche reduction of acyclic and cyclic alpha, beta-epoxy ketones.

(Z)-24(28)-Dehydro-oogoniol, a steroid sex hormone isolated from the water mold Achyla (a primitive eukaryote), has been synthesized from dehydroadrenosterone in 24 steps with an overall yield of 8.1%. The reactions involved in this synthesis are highly regio- and stereoselective. The key steps include: (1) the CuCN-catalyzed addition of CH$\sb2$=CHMgBr onto a steroidal allylic epoxide, (E)-$3{\beta},11\alpha$a-bis(t-butyldimethyl-silyloxy)-$15{\beta},16\beta$-epoxypregna-5,17(20)-diene, obtained from adrenosterone in 13 steps in 40% overall yield and (2) the CuI-catalyzed alkylation of the alkenyl Grignard reagent generated by the highly stereoselective hydromagnesiation of 4-methyl-2-pentyn-1-ol with the 23-steroidal iodide derivatized from the epoxide opening product. The Luche reduction of both acyclic and cyclic $\alpha,\ \beta$-epoxy ketones has also been studied. Reduction of acyclic $\alpha,\ \beta$-epoxy ketones with sodium borohydride in methanol gives only modest diastereoselectivity. However, in the presence of one equivalent of cerium chloride, this same reducing reagent provides anti- (or erythro-) $\alpha,\ \beta$-epoxy alcohols with extremely high diasteroselectivity, as has been observed for Zn(BH$\sb4)\sb2$-reductions. A chelated transition state similar to that of Zn(BH$\sb4)\sb2$-reduction has been proposed. The Luche reduction of cyclic $\alpha,\ \beta$-epoxycyclohexanones gives predominantly ($>$19/1) the corresponding trans-$\alpha,\ \beta$-epoxy alcohols with the exception of those which have 2-alkyl and/or 5-cis-alkyl/alkenyl groups. A pull-push type of reaction mechanism has been proposed for the reduction of the cyclic $\alpha,\ \beta$-epoxy ketones.PhDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/104167/1/9500984.pdfDescription of 9500984.pdf : Restricted to UM users only