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

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.

Key words

carbocations - carbocycles - rearrangements - thioacetals

References

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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 Z→E 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.