Synlett 2004(8): 1387-1393  
DOI: 10.1055/s-2004-825613
LETTER
© Georg Thieme Verlag Stuttgart · New York

Scope and Limitations of the Thionium Ion-Initiated Prins-Pinacol Synthesis of Carbocycles

Brenda J. Burke, Alec D. Lebsack, Larry E. Overman*
Department of Chemistry, University of California, 516 Rowland Hall, Irvine, CA 92697-2025, USA
Fax: +1(949)8243866; e-Mail: leoverma@uci.edu;
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Publikationsverlauf

Received 19 October 2003
Publikationsdatum:
18. Mai 2004 (online)

Abstract

cis-Bicyclo[5.3.0]decanones and cis-bicyclo[6.3.0]undecanones containing two side chains in their five-membered rings can be prepared from cyclohexanone and cycloheptanone precursors, respectively. The structural features required for these thio-Prins-pinacol reactions are delineated.

1

Current address: Merck & Co., Inc., 3535 General Atomics Court, MRLSDB2, San Diego, CA 92121-1140, USA.

5

These reactivity trends are also seen in cyclizations of congeneric substrates having 1-alkynyl substituents, see ref. [4b]

12

The trimethylsilyl congeners of propargyl alcohols 13b and 14b were found to be labile under the thio-Prins-pinacol reaction conditions, therefore the TBDMS ethers were used instead.

14

Attempted silylation of these allylic alcohols with(trimethylsilyl)imidazole at 120 °C surprisingly resulted in partial ZE isomerization of the double bond.

15

It was crucial to rigorously exclude water from these hydride reductions to prevent competing reduction of the diphenylthio acetal to the corresponding phenylsulfide, a transformation likely catalyzed by trivalent aluminum species resulting from reaction of Red-Al® with trace amounts of water.

16

Attempts to derivatize 13a and 14a to obtain a crystalline product were unsuccessful. Similarly, NMR studies to establish the relative configurations of these epimers were inconclusive because of the lack of conformational rigidity in these molecules.

19

cis-Fused lactone 20 likely exists in two low energy chair conformations. Molecular mechanics calculations show that these substituents are 4.1-4.6 Å apart in these conformations, whereas they are separated by 6.7 Å in 18.

21

Crystallographic data for this compound was deposited at the Cambridge Crystallographic Data Centre: CCDC 221821.

23

Cyclohexanones 27 were identified by 1H NMR, COSY NMR, and mass spectrometry.

24

These two trace hydroazulenone products were identified by mass spectrometry and 1H NMR analysis. Neither of these products was hydroazulenone 26.

25

An isomer of 31 with uncertain structure was also isolated in 7% yield; it was not a stereoisomer of 31.

26

Trace amounts of alkene-containing products were detected in 1H NMR spectra of the crude reaction mixtures.

28

Doublets in the 1H NMR spectra of the crude reaction mixture attributable to the methyl substituent of hydroazulenone 36, or a stereoisomer, were not observed.