with nucleophiles, thus including epoxidation of olefins, enolate-
mediated hydroxylation of carbonyl compounds and oxidation
of sulfides to sulfoxides.4
trans-(()-2-tert-Butyl-3-phenyloxaziridine: A
Unique Reagent for the Oxidation of Thiolates
into Sulfenates
Ce´dric Boudou,† Matthieu Berge`s,† Charle`ne Sagnes,†
Jana Sopkova´-de Oliveira Santos,‡ Ste´phane Perrio,*,† and
Patrick Metzner†
Laboratoire de Chimie Mole´culaire et Thio-organique,
ENSICAEN, UniVersite´ de Caen Basse-Normandie, CNRS, 6
BouleVard du Mare´chal Juin, 14050 Caen, France, and Centre
d’Etudes et de Recherche sur le Me´dicament de Normandie,
UniVersite´ de Caen Basse-Normandie, 5 Rue Vaube´nard,
14032 Caen, France
A few years ago, an original5 synthetic utility involving
lithium thiolates (R1S-) as substrates was reported by our group6
which allowed an efficient and straightforward7 access to the
corresponding sulfenate salts (R1SO-) (Scheme 1). The unusual
N-sulfonyloxaziridine 1a derived from pinacolone was thus
introduced as the ideal reagent. Treatment in situ with aliphatic
halides led to sulfoxides 3 in good to excellent yields. The scope
of the reaction sequence is broad with successful applications
toward aryl, 1-alkenyl, and 1-alkynyl species. In contrast,
extension of the protocol with the more nucleophilic alkanethi-
olates (R1 ) alkyl) failed. Instead of the desired monooxidation
product, the sulfinate salt (R1SO2Li) was isolated as a conse-
quence of an unwanted double oxidation reaction. Similar
disappointing results were also obtained with a screening of a
range of milder N-sulfonyl derivatives,8 thus exemplifying the
difficulty to control the sulfenate oxidation stage.9
ReceiVed April 6, 2007
Aliphatic thiolates were efficiently converted into the cor-
responding sulfenates by smooth oxidation with trans-(()-
2-tert-butyl-3-phenyloxaziridine at room temperature (five
examples). Subsequent electrophilic quench with benzyl
bromide led to sulfoxides (S-alkylation) in good to moderate
yields. Application of the protocol to an aromatic substrate
was also successful. This work represents the first valuable
example of the use of this poorly active oxidizing agent in
synthetic organic chemistry without the need for activating
conditions.
(3) Perfluorinated oxaziridines: (a) Petrov, V. A.; Resnati, G. Chem.
ReV. 1996, 96, 1809-1824. Alkoxysulfonyl oxaziridines: (b) Brodsky, B.
H.; Du Bois, J. J. Am. Chem. Soc. 2005, 127, 15391-15393. Related
oxaziridinium salts: (c) Poisson, D.; Cure, G.; Solladie´, G.; Hanquet, G.
Tetrahedron Lett. 2001, 42, 3745-3748. (d) Lacour, J.; Monchaud, D.;
Marsol, C. Tetrahedron Lett. 2002, 43, 8257-8260. (e) Page, P. C. B.;
Rassias, G. A.; Barros, D.; Ardakani, A.; Buckley, B.; Bethell, D.; Smith,
T. A. D.; Slawin, A. M. Z. J. Org. Chem. 2001, 66, 6926-6931.
(4) (a) Davis, F. A. J. Org. Chem. 2006, 71, 8993-9003. (b) Davis, F.
A.; Haque, M. S. Oxygen-Transfer Reactions of Oxaziridines. In AdVances
in Oxygenated Processes; Baumstark, A. L., Ed.; JAI Press, Inc.: Greenwich
1990; Vol. 2, pp 61-116. (c) Ishimaru, T.; Shibata, N.; Nagai, J.; Nakamura,
S.; Toru, T.; Kanemasa, S. J. Am. Chem. Soc. 2006, 128, 16488-16489.
(5) The oxidation of thiolates into sulfenates is not a common reaction
in organic synthesis: (a) O’Donnell, J. S.; Schwan, A. L. J. Sulfur Chem.
2004, 25, 183-211. In contrast, this reaction is more encountered in biology,
especially with processes involving cysteine residues: (b) Forman, H. J.;
Fukuto, J. M.; Torres, M. Am. J. Physiol. Cell. Physiol. 2004, 287, C246-
C256. (c) Nagahara, N.; Katayama, A. J. Biol. Chem. 2005, 280, 34569-
34576.
Since their discovery 50 years ago, oxaziridines 1, character-
ized by a reactive strained C, N, O three-membered ring, have
been widely investigated in organic synthesis as both aminating
and oxygenating agents.1 The predominance of one process over
another is significantly affected by varying the substitution
pattern on the nitrogen atom. It has been established that the
amino group transfer is the normal pathway for N-H, N-alkyl,
N-acyl, and N-alkoxycarbonyl systems.2 In contrast, a shift of
reactivity toward the oxygen center3 is observed with structures
possessing bulky or electron-withdrawing groups, from which
N-sulfonyl derivatives have particularly emerged. These reagents
have been extensively used in various oxygen transfer reactions
(6) (a) Sandrinelli, F.; Perrio, S.; Beslin, P. J. Org. Chem. 1997, 62,
8626-8627. (b) Sandrinelli, F.; Perrio, S.; Averbuch-Pouchot, M.-T. Org.
Lett. 2002, 4, 3619-3622. (c) Sandrinelli, F.; Fontaine, G.; Perrio, S.; Beslin,
P. J. Org. Chem. 2004, 69, 6916-6919. (d) Sandrinelli, F.; Boudou, C.;
Caupe`ne, C.; Averbuch-Pouchot, M.-T.; Perrio, S.; Metzner, P. Synlett 2006,
3289-3293.
(7) Alternative routes to sulfenate species consist of manipulation of
sulfoxides possessing an appropriate functionality, the most relevant
contributions being the oxidative cleavage of 1-alkynyl sulfoxides with a
Pd(0)-catalyst followed by transmetalation with Et2Zn, an addition/
elimination methodology with â-sulfinylacrylates, a retro-Michael reaction
initiated by a base from â-sulfinyl esters, and finally, the fluoride-mediated
deprotection of 2-(trimethylsilyl)ethyl sulfoxides. See ref 5a and: (a)
Caupe`ne, C.; Boudou, C.; Perrio, S.; Metzner, P. J. Org. Chem. 2005, 70,
2812-2815. (b) Maitro, G.; Prestat, G.; Madec, D.; Poli, G. J. Org. Chem.
2006, 71, 7449-7454. (c) Maitro, G.; Vogel, S.; Prestat, G.; Madec, D.;
Poli, G. Org. Lett. 2006, 8, 5951-5954. (d) Foucoin, F.; Caupe`ne, C.;
Lohier, J.-F.; Sopkova´-de Oliveira Santos, J.; Perrio, S.; Metzner, P.
Synthesis 2007, 1315-1324.
* To whom correspondence should be addressed. Phone: Int. code +23145-
2884. Fax: Int. code +23145-2877.
† Laboratoire de Chimie Mole´culaire et Thio-organique.
‡ Centre d’Etudes et de Recherche sur le Me´dicament de Normandie.
(1) (a) Mishra, J. K. Synlett 2005, 543-544. (b) Davis, F. A.; Sheppard,
A. C. Tetrahedron 1989, 45, 5703-5742.
(2) (a) Page, P. C. B.; Limousin, C.; Murrell, V. L. J. Org. Chem. 2002,
67, 7787-7796. (b) Armstrong, A.; Challinor, L.; Cooke, R. S.; Moir, J.
H.; Treweeke, N. R. J. Org. Chem. 2006, 71, 4028-4030. (c) Choong, I.
C.; Ellman, J. A. J. Org. Chem. 1999, 64, 6528-6529. (d) Vidal, J.;
Damestoy, S.; Guy, L.; Hannachi, J.-C.; Aubry, A.; Collet, A. Chem. Eur.
J. 1997, 3, 1691-1709. (e) Armstrong, A.; Edmonds, I. D.; Swarbrick, M.
E.; Treweeke, N. R. Tetrahedron 2005, 61, 8423-8442.
10.1021/jo070700n CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/09/2007
J. Org. Chem. 2007, 72, 5403-5406
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