SCHEME 1
Oxaziridine-Mediated Amination of Branched
Allylic Sulfides: Stereospecific Formation of
Allylic Amine Derivatives via [2,3]-Sigmatropic
Rearrangement
Alan Armstrong,*,† Lee Challinor,† Richard S. Cooke,†
Jennifer H. Moir,‡ and Nigel R. Treweeke†
Department of Chemistry, Imperial College London,
South Kensington, London SW7 2AZ, U.K., and
Organon Newhouse, Lanarkshire ML1 5SH, Scotland
bearing radical-stabilizing groups (e.g., R2 ) CO2Me) due to
competing homolytic cleavage of the allylic C-S bond.4
Pleasingly, these substrates gave good results with oxaziridine
1.1a Bach also made interesting stereochemical observations
when using branched allylic sulfides (2, R1 * H). While the
[2,3]-sigmatropic rearrangement would be expected to proceed
with a high degree of chirality transfer,5 as has been observed
with N-sulfonylallylic sulfimides,6 Bach obtained products of
eroded ee when enantiomerically pure branched allylic sulfides
were used in his BocN3/FeCl2 system (Scheme 1). While the
poor ee of 3a could be rationalized by possible product
epimerization, this explanation is unlikely for 3b; furthermore,
it was discovered that recovered starting material 2b had a
deteriorated enantiopurity (75% ee). In addition to partial
substrate racemization, Bach postulated that the stereogenic
center at sulfur in the intermediate N-Boc-allylic sulfimides may
influence the stereochemical outcome of the reactions. As our
oxaziridine system is mechanistically distinct to Bach’s Fe-
catalyzed chemistry, we were interested in testing these more
demanding branched substrates in order to determine whether
efficient and stereocontrolled rearrangement would be possible.
Our initial studies focused on reactions of racemic R-branched
phenyl sulfides 2a and 2b. In view of the high chemoselectivity
observed earlier with unbranched phenylsulfides 2 (R1 ) H)
with 1,1a we were initially surprised that attempted amination-
rearrangement of rac-2a led not only to the expected allylic
amine derivative rac-3a (30%), but also to large quantities of
sulfoxide (60%, mixture of diastereomers). A relatively low
yield (55%) was also obtained for amination/rearrangement of
rac-2b. The low level of chemoselectivity is most likely due to
steric factors: Collet has demonstrated that increasing the size
of the oxaziridine N-substituent generally leads to higher levels
of oxidation versus amination,7 and it is reasonable to expect
that steric hindrance in the substrate would have the same effect.
In line with this idea, we found that while phenyl ethyl sulfide
ReceiVed February 22, 2006
Reaction of branched allylic sulfides with the N-Boc-
oxaziridine 1 results in [2,3]-sigmatropic rearrangement of
the intermediate allylic N-Boc-sulfimides with a high level
of chirality transfer. The first example of formation of a
quaternary stereocenter using this transformation is reported.
We have recently developed the novel oxaziridine reagent 1
and demonstrated that it will effect efficient conversion of
sulfides to N-Boc-sulfimides under metal-free conditions.1,2
Reagents which, like 1, efficiently transfer electrophilic nitrogen
with a carbamate protecting group are rare.3 We have also shown
that this reagent will effect amination of allylic sulfides, leading
to allylic amine products via [2,3]-sigmatropic rearrangement
of the intermediate allylic sulfimide (Scheme 1).1a These results
extended the scope of the rearrangement since the only prior
report of the N-carbamate variant of this chemistry, from Bach’s
group and using BocN3/FeCl2, gave poor yields with substrates
(3) For reviews of electrophilic amination, see: (a) Erdik, E.; Ay, M.
Chem. ReV. 1989, 89, 1947. (b) Greck, C.; Genet, J. P. Synlett. 1997, 741.
(c) Mulzer, J.; Altenbach, H. J. In Organic Synthesis Highlights; VCH:
Weinheim, 1991; p 45. (d) Dembach, P.; Seconi, G.; Ricci, A. Chem. Eur.
J. 2000, 6, 1281. (e) Modern Amination Methods; Ricci, A., Ed.; Wiley-
VCH: Weinheim, 2000. (f) Erdik, E. Tetrahedron 2004, 60, 8747. (g) Greck
C, Drouillat B, Thomassigny, C. Eur. J. Org. Chem. 2004, 7, 1377. For a
recently reported catalytic method for preparing N-(trifluoroacetyl)sulfim-
ides, see: (e) Tomooka, C. S.; LeCloux, D. D.; Sasaki, H.; Carreira, E. M.
Org. Lett. 1999, 1, 149.
(4) (a) Bach, T.; Ko¨rber, C. Eur. J. Org. Chem. 1999, 1033. (b) Bach,
T.; Ko¨rber, C. J. J. Org. Chem. 2000, 65, 2358.
(5) (a) Bravermann, S. Int. J. Sulfur Chem. 1971, C6, 149. (b) Hoffmann,
R. W. Angew. Chem., Int. Ed. Engl. 1979, 18, 563.
* To whom correspondence should be addressed. Fax: +44 (0) 20 75945804.
Tel: +44 (0) 20 75945876.
† Imperial College London.
‡ Organon Newhouse.
(1) (a) Armstrong, A.; Cooke, R. S. Chem. Commun. 2002, 904. (b)
Armstrong, A.; Cooke, R. S.; Shanahan, S. E. Org. Biomol. Chem. 2003,
1, 3142. (c) Armstrong, A.; Jones, L. H.; Knight, J. D.; Kelsey, R. D. Org.
Lett. 2005, 7, 713.
(2) For reviews of sulfimide chemistry, see: (a) Taylor, P. C. Sulfur
Rep. 1999, 21, 241. (b) Gilchrist, T. L.; Moody, C. J. Chem. ReV. 1977,
77, 409. For some recent examples of sulfimidation, see: (c) Marzinzik,
A. L.; Sharpless, J. Org. Chem. 2001, 66, 594 and references therein. (d)
Takada, H.; Nishibashi, Y.; Ohe, K.; Uemura, S.; Baird, C. P.; Sparey, T.
J.; Taylor, P. C. J. Org. Chem. 1997, 62, 6512.
(6) (a) Dolle, R. E.; Osifo, K. I.; Li, C.-S. Tetrahedron Lett. 1991, 32,
5029. (b) Dolle, R. E.; Li, C.-S.; Novelli, R.; Kruse, L. I.; Eggleston, D. J.
Org. Chem. 1992, 57, 128.
(7) Vidal, J.; Damestoy, S.; Guy, L.; Hannachi, J.-C.; Aubry, A.; Collet,
A. Chem. Eur. J. 1997, 3, 1691.
10.1021/jo060369s CCC: $33.50 © 2006 American Chemical Society
Published on Web 03/28/2006
4028
J. Org. Chem. 2006, 71, 4028-4030