ORGANIC
LETTERS
2001
Vol. 3, No. 20
3121-3124
Use of Odorless Thiols: Formal
Asymmetric Michael Addition of
Hydrogen Sulfide to r-Substituted
r,â-Unsaturated Carbonyl Compounds
Kiyoharu Nishide, Shin-ichi Ohsugi, Hiroaki Shiraki, Hirokazu Tamakita, and
Manabu Node*
Department of Pharmaceutical Manufacturing Chemistry,
Kyoto Pharmaceutical UniVersity, Misasagi, Yamashina, Kyoto 607-8414, Japan
Received July 9, 2001
ABSTRACT
The Michael addition to r-substituted r,â-unsaturated esters and amides using complex A containing a chiral odorless thiol proceeded
diastereoselectively. The Michael adducts were converted to â-mercapto esters and amides via a Wagner−Meerwein rearrangement with boron
trifluoride etherate and a thiol exchange reaction using odorless 1-dodecanethiol. This conversion constitutes a formal asymmetric Michael
addition of hydrogen sulfide to r,â-unsaturated carbonyl compounds using odorless thiols instead of the toxic hydrogen sulfide.
The Michael addition of a thiol to R,â-unsaturated carbonyl
compounds is a fundamental reaction in organic chemistry.1
From the standpoint of asymmetric synthesis, this reaction
essentially consists of an asymmetric 1,4-addition and an
asymmetric protonation. Excellent diastereoselective2 and
enantioselective3 Michael additions of thiols to R,â-unsatur-
ated carbonyl compounds have been extensively studied.
However, the enantioselective protonation of enolates and
enols has only recently been recognized as a promising
method for the construction of a tertiary carbon center in
asymmetric synthesis.4 Therefore, much effort has been
focused on the enantioselective protonation of the enolates
derived from the parent carbonyl compounds.4 Only a few
studies have been reported on the reaction of the enolates
generated by 1,4-addition of a thiolate anion to R,â-
unsaturated carbonyl compounds.3g,h,5 Thiophosphonates of
1,1′-binaphthol as chiral equivalents of hydrogen sulfide were
used in radical additions to strained alkenes but with low
diastereoselectivity.6a Recently, Palomo et al. reported an
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(4) (a) Fehr, C. Angew. Chem., Int. Ed. Engl. 1996, 35, 2566-2587. (b)
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see the references therein.
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319, 219-229. (b) Kobayashi, N.; Iwai, K. J. Am. Chem. Soc. 1978, 100,
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Chem. Soc., Chem. Commun. 1991, 485-486. (d) Miyata, O.; Shinada, T.;
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10.1021/ol016406d CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/31/2001