A TOTAL SYNTHESIS OF 1-OXYGENATED STEROIDS¹

Designing Total Syntheses

“…The first of these (BC -» ABC -» ABCD), discussed in Chapter 9, is illustrated by the conversion of 25 (Scheme 1-3) to the pregnane derivative 28 [43]. Annelation of 25 to 29 followed by a second annelation to 30 constitutes the reverse route (BC -> BCD -> ABCD) [44] (Chapter 10).…”

“…* In the synthesis of 11-oxosteroids, 61 (Scheme 1-6), was alkylated with 3-benzyloxy-l-butyl bromide; the benzyloxy group is a potential car-* Cyclization of a-haloketals is a new annelation procedure subject to remarkable steric control: G. Stork bonyl, but in this case the protective group is more cumbersome to remove than are ketal groups. A second alkylation step employed methyl iodide to provide the angular methyl group, producing 63 and its C-10 epimer in about equal amounts [44]. The dichlorophenyl ether 64 and the chlorophenyl thioether 65 also have been developed as annelating agents [11].…”

“…The 13-methyl homolog, 101, of 87 (Scheme 1-8) reacted with 4-penten-l-ylmagnesium bromide to produce a 90% yield of the eis and trans isomers 102 [90]. The lactone 103 (prepared by ozonolysis of the tricyclic ketone 61) (Scheme 1-6) reacted with 4-methyl-4penten-1-ylmagnesium bromide to give the secosteroid 104 [44]. The naphthalene Grignard reagent 105 reacted with the isobutyl enol ether of 2-methylcyclopentane-l,3-dione to give a good yield of the ABD intermediate 106 [91].…”

Bc → BCD → Abcd

“…A remarkably short and flexible route to 11-oxygenated steroids was developed by Stork and co-workers [114] (Scheme 10-12). 6-Methoxy-ltetralone (156, R = H) was first converted via the hydroxymethylene ketone to the 2-methyl derivative 157 (R = H).…”

Cd → BCD → Abcd

“…The precise amount of ß-methyl product obtained was not determined, but was considered to be at least 46% based on the 38% conversion of 163 into 166 [116,118]. This latter figure was a considerable improvement over the previous method; however, the attractiveness of the overall scheme was lessened by the poor yields and the difficulty in handling some of the prior intermediates obtained when working with tricyclic materials substituted with the carboxyethyl function in place of the methyl group.…”