ORGANIC
LETTERS
2012
Vol. 14, No. 3
942–945
Electrochemical Cleavage of
Sulfonamides: An Efficient and Tunable
Strategy to Prevent β-Fragmentation and
Epimerization
Pierre Viaud, Vincent Coeffard, Christine Thobie-Gautier, Isabelle Beaudet,
Nicolas Galland, Jean-Paul Quintard,* and Erwan Le Grognec*
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Universite de Nantes, CNRS, Chimie Et Interdisciplinarite: Synthese, Analyse et
Modelisation (CEISAM), UMR CNRS 6230, Faculte des Sciences et des Techniques,
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2, rue de la Houssiniere, BP 92208, 44322 Nantes Cedex 3, France
jean-paul.quintard@univ-nantes.fr; erwan.legrognec@univ-nantes.fr
Received January 3, 2012
ABSTRACT
The electrochemical reduction of sensitive sulfonamides is described. The addition of a benzoyl group on the nitrogen atom facilitates the
reductive cleavage of sulfonamides preventing β-fragmentation and epimerization. This strategy was successfully applied to the
cyclopropylamine and to R-amino stannanes.
Sulfonamides play a pivotal role in amine chemistry, not
only as a class of nitrogen protecting groups but also as
activatinggroupsor derivatization reagents.1 Inparticular,
N-arenesulfonyl groups are highly valued in synthetic
chemistry for their ease of introduction, robustness,
unreactivity toward a large range of nucleophiles, and
the high crystallinity of the corresponding amino com-
pounds. However, their major drawback lies in their
removal which often requires harsh conditions thus low-
ering their synthetic appeal. Although several chemical
deprotection methods of amines bearing an arenesulfonyl
group have been reported,2 the selective deprotection of
functionalized molecules still remains a challenge. Be-
sides chemical methods, electrochemical reduction
has also emerged as a mild and tunable alternative
for the cleavage of arenesulfonamides.3 For instance, we
have recently applied an electrochemical reduction for the
(1) (a) Wuts, P. G. M.; Greene, T. W. Greene’s Protective Groups in
Organic Synthesis, 4th ed.; Wiley-Interscience: New York, 2006. (b)
Kocienski, P. J. Protecting Groups, 3rd ed.; Georg Thieme Verlag: New
York, 2005.
(2) For selected examples, see: SmI2: (a) Vedejs, E.; Lin, S. J. Org.
Chem. 1994, 59, 1602–1603. (b) Kuriyama, M.; Soeta, T.; Hao, X.; Chen, Q.;
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Moussa, Z.; Romo, D. Synlett 2006, 3294–3298. (g) Kong, K.; Romo, D.;
Lee, C. Angew. Chem., Int. Ed. 2009, 48, 7402–7405. Bu3SnH/AIBN:
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(i)Knowles, H. S.; Parsons, A. F.;Pettifer, R. M.; Rickling, S.Tetrahedron
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Olivero, S. New. J. Chem. 2006, 30, 1534–1548. (b) Yoshida, J.-i.;
Kataoka, K.; Horcajada, R.; Nagaki, A. Chem. Rev. 2008, 108, 2265–
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Vasquez-Medrano, R. Green Chem. 2010, 2099–2119. For selected
examples on electrochemical desulfonylation, see: (a) Horner, L.; Neumann,
H. Chem. Ber. 1965, 98, 3462–3469. (b) Mairanovsky, V. G. Angew.
Chem., Int. Ed. Engl. 1976, 15, 281–291. (c) Lebouc, A.; Martigny, P.;
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E. R.; Rapoport, H. J. Org. Chem. 1992, 57, 834–840. (e) Lund, H.;
Hammerich, O. Organic Electrochemistry, 4th ed.; Marcel Dekker: New
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435–438.
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10.1021/ol300003f
Published on Web 01/24/2012
2012 American Chemical Society