ORGANIC
LETTERS
2006
Vol. 8, No. 17
3785-3788
Efficient N-Heterocyclic
Carbene-Catalyzed O- to C-Acyl Transfer
Jennifer E. Thomson, Kathryn Rix, and Andrew D. Smith*
EaStChem, School of Chemistry and Centre for Biomolecular Sciences,
UniVersity of St Andrews, North Haugh, St Andrews, KY16 9ST, U.K.
Received June 6, 2006
ABSTRACT
An N-heterocyclic carbene promotes the rearrangement of
r-amino acid derived O-acyl carbonates to their corresponding C-acylated isomers,
generating a C C bond and a quaternary stereocenter with high efficiency, under mild reaction conditions and with low catalyst loadings.
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N-Heterocyclic carbenes (NHCs) have recently been shown
to promote a range of organocatalytic reactions.1 Within this
rapidly expanding field of research, two mechanistically
distinct reaction pathways are widely recognized, involving
the use of NHCs as either acyl anion equivalents or acyl
transfer reagents. The ability of NHCs to generate acyl anion
equivalents for C-C bond-forming applications has been
demonstrated for benzoin- and Stetter-type transformations2
and has been extended to nucleophilic substitution3 and
homoenolate reactions,4 although these reaction protocols
typically require >5 mol % of catalyst. NHCs have been
utilized as catalytic acyl transfer agents to promote trans-
esterification reactions,5-7 and these methods have been
extended to the kinetic resolution of racemic alcohols using
chiral NHCs.8 Although these resolutions proceed with high
levels of stereoselectivity, relatively high catalyst loadings
(typically 5-30 mol %) and long reaction times (up to 48
h) are needed to achieve significant reaction conversion. To
date, applications of NHCs as catalytic acyl transfer reagents
have been limited to acyl transfer to alcohols;9 to the best
of our knowledge, their application in truly catalytically
(4) For selected examples, see: Burstein, C.; Glorius, F. Angew. Chem.,
Int. Ed. 2004, 43, 6205. Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am.
Chem. Soc. 2004, 126, 14370. Chan, A.; Scheidt, K. A. Org. Lett. 2005, 7,
905.
(5) Grasa, G. A.; Kissling, R. M.; Nolan, S. P. Org. Lett. 2002, 4, 3583.
Grasa, G. A.; Gu¨veli, T.; Singh, R.; Nolan, S. P. J. Org. Chem. 2003, 68,
2812.
(6) Connor, E. F.; Nyce, G. W.; Myers, M.; Mo¨ck, A.; Hedrick, J. L. J.
Am. Chem. Soc. 2002, 124, 914. Nyce, G. W.; Lamboy, J. A.; Connor, E.
F.; Waymouth, R. M.; Hedrick, J. L. Org. Lett. 2002, 4, 3587. Nyce, G.
W.; Glauser, T.; Connor, E. F.; Mo¨ck, A.; Waymouth, R. M.; Hedrick, J.
L. J. Am. Chem. Soc. 2003, 125, 3046.
(7) Movassaghi and Schmidt have proposed that NHCs function as
carbon-centred Bronsted bases: Movassaghi, M.; Schmidt, M. A. Org. Lett.
2005, 7, 2453.
(8) Suzuki, Y.; Maramatsu, K.; Yamauchi, K.; Morie, Y.; Sato, M. Chem.
Commun. 2004, 2770. Kano, T.; Sasaki, K.; Maruoka, K. Org. Lett. 2005,
7, 1347. Suzuki, Y.; Maramatsu, K.; Yamauchi, K.; Morie, Y.; Sato, M.
Tetrahedron 2006, 62, 302.
(1) For selected reviews, see: Enders, D.; Balensiefer, T. Acc. Chem.
Res. 2004, 37, 534. Johnson, J. S. Angew. Chem., Int. Ed. 2004, 43, 1326.
(2) Teles, J. H.; Melder, J.-P.; Ebel, K.; Schneider, R.; Gehrer, E.; Harder,
W.; Brode, S.; Enders, D.; Breuer, K.; Raabe, G. HelV. Chim. Acta 1996,
79, 61. Enders, D.; Breuer, K.; Teles, J. H. HelV. Chim. Acta 1996, 79,
1217. Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H. HelV. Chim. Acta
1996, 79, 1899. Enders, D.; Kallfass, U. Angew. Chem., Int. Ed. 2002, 41,
1743. Kerr, M. S.; de Alaniz, J. R.; Rovis, T. J. Am. Chem. Soc. 2002, 124,
10298. Chow, K. Y. K.; Bode, J. W. J. Am. Chem. Soc. 2004, 126, 8216.
Reynold, N. T.; de Alaniz, J. R.; Rovis, T. J. Am. Chem. Soc. 2004, 126,
9518. Myers, M. C.; Bharadwaj, A. R.; Milgram, B. C.; Scheidt, K. A. J.
Am. Chem. Soc. 2005, 127, 14675.
(3) Suzuki, Y.; Toyota, T.; Imada, F.; Sato, M.; Miyashita, A. Chem.
Commun. 2003, 1314.
10.1021/ol061380h CCC: $33.50
© 2006 American Chemical Society
Published on Web 07/15/2006