Transition-Metal-Catalyzed Alkyne Cyclizations. A Cobalt-Mediated Total Synthesis of dl-Estrone

Raymond Lee Funk, K. Peter C. Vollhardt

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Abstract

A cobalt-catalyzed total synthesis of racemic steroids (including estrone 1) is described based on the cooligomerization of substituted 1,5-hexadiyne 3 with monoalkynes. An unsuccessful strategy for the synthesis of starting material 3 via chloroethyl derivative 18 was abandoned in favor of a convergent synthesis via 3-(2-iodoethyl)- 1,5-hexadiyne (19) on one hand and enol ether 20 on the other. Compound 3 reacted with BTMSA in the presence of CpCo(CO)2 to give racemic 2,3-bis(trimethylsilyl) estratrienone (24a) via benzocyclobutenes 23. Similarly, 3 cyclized with trimethylsilyl(methoxy)ethyne to furnish in low yield (via benzocyclobutene intermediates) steroids 24c,d, the former providing -estrone methyl ether on protodesilylation. Estrone could be obtained with poor regiochemical control from ketal 33 by bromination, followed by conversion of the bromine moiety to a hydroxyl group. However, selective protodesilylation of 24a at low temperatures to 3-trimethylsilylestratrienone (24g) followed by oxidative cleavage of the phenyl-silicon bond with Pb(OOCCF3)4 gave 1: five steps from 2-methylcyclopentenone (21.5%) and six steps from 1,5-hexadiyne (15.1%). A slight improvement of yields is realized via cyclization of the ethylene ketal 29 (23.1 and 16.2%, respectively).

Original languageEnglish (US)
Pages (from-to)5253-5261
Number of pages9
JournalJournal of the American Chemical Society
Volume102
Issue number16
DOIs
StatePublished - Jan 1 1980

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All Science Journal Classification (ASJC) codes

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

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