Preparation of a 6a-substituted optically pure steroid with thiophene as the A ring via asymmetric induction. A circular dichroism study

A.A. Macco, H.M. Buck

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

A number of asymmetrically induced cyclization reactions are described, furnishing specifically substituted steroid-like systems with thiophene as the A ring. Ring closure of achiral compounds gives two enantiomeric trans-anti-fused products, containing three chiral carbon atoms each. The presence of a nonepimerizable chirality in the cyclization precursor favors production of one ring-closed diastereomer over the other. A comparable example of an in vivo ring closure is found in the conversion of 2,3-epoxysqualene to various steroids. A chiral center far removed from the cyclization initiator also influences the stereochemical outcome of such cyclizations. A deuterium at pro-C-6 (steroid numbering) causes no measurable asymmetrically induced ring closure because of the deuterium's comparable size to a hydrogen atom. A methyl group at pro-C-6, however, will cause ring closure to proceed in 97% yield to a 6a-substituted steroid. A 100% asymmetrically induced ring closure in favor of the 6a-substituted products is brought about by a t-Bu group. Aforementioned stereospecificities are believed to stem from 1,3-diaxial interactions between the substituent at the chiral carbon atom and the pro-C-8 and pro-C-10 hydrogen atoms. This gives rise to a model description of the ring closure in terms of "precoiling". The ring closure of the optically pure tert-butyl-substituted alkene gives an optically pure steroid, since the reaction proceeds with 100% asymmetric induction. Hereby, a significant yield increase is observed (50% --+ 80%). The absolute configurations of the precursors and the cyclized products are determined by circular dichroism.
Original languageEnglish
Pages (from-to)2655-2660
Number of pages6
JournalJournal of Organic Chemistry
Volume46
Issue number13
DOIs
Publication statusPublished - 1981

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