Photolysis of α-Peracetoxynitriles. 2.1A Comparison of Two Synthetic Approaches to 18-Cyano-20-ketosteroids

Robert W. Freerksen, W. Edward Pabst, Michael L. Raggio, Steven A. Sherman, Randall R. Wroble, David S. Watt

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40 Scopus citations

Abstract

A new photochemical reaction was utilized to functionalize unactivated carbon-hydrogen bonds in the C-18 angular methyl group in steroids. The photolysis of 20-peracetoxy-20-cyanosteroids derived from 17-ketosteroids furnished 18-cyano-20-ketosteroids. For example, the following sequence of reactions was applied to 3Β-hydroxyandrost-5-en-17-one (11): (1) protection of the hydroxyl group in 11 using isobutylene-sulfuric acid to furnish 3Β-tert-butoxyandrost-5-en-l7-one (12), 73% yield; (2) condensation of 12 with the anion of 2-(diethylphosphono)propionitrile to afford 3Β-tert-butoxy-20-carboni-trilepregna-5,17(20)-diene (13), 74% yield; (3) magnesium in methanol reduction of 13 to provide 3Β-tert-butoxy-20-carboni-trilepregn-5-ene (14), 85% yield; (4) sequential treatment of 14 with lithium diisopropylamide, oxygen gas, and acetyl chloride to obtain 3Β-tert-butoxy-20-carbonitrile-20-peracetoxypregn-5-ene (15), 62% yield; and (5) the photolysis of 15 to furnish 3Β-tert-butoxy-18-carbonitrilepregn-5-en-20-one (16), 46% yield. In the same manner, 20-carbonitrile-20-peracetoxypregn-5-en-3-one ethylene ketal (22) afforded 18-carbonitrilepregn-5-ene-3,20-dione 3-ethylene ketal (23) in 21% yield, and 20-car-bonitrile-3-methoxy-20-peracetoxy-19-norpregna-1,3,5(10)-triene (31) furnished 18-carbonitrile-3-methoxy-19-norpregna-l,3,5(10)-trien-20-one (33) in 39% yield. Finally, the new photochemical approach to 18-cyano-20-ketosteroids was contrasted with the cyanohydrin-ketonitrile reaction developed by Kalvoda.

Original languageEnglish
Pages (from-to)1536-1542
Number of pages7
JournalJournal of the American Chemical Society
Volume99
Issue number5
DOIs
StatePublished - 1977

ASJC Scopus subject areas

  • Catalysis
  • Chemistry (all)
  • Biochemistry
  • Colloid and Surface Chemistry

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