ORGANIC
LETTERS
2005
Vol. 7, No. 7
1347-1349
Enantioselective Acylation of Secondary
Alcohols Catalyzed by Chiral
N-Heterocyclic Carbenes
Taichi Kano, Kouji Sasaki, and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo, Kyoto 606-8502, Japan
Received January 27, 2005
ABSTRACT
The synthetic utility of chiral N-heterocyclic carbenes, which have been used mainly in transition metal-catalyzed reactions as a ligand, was
demonstrated by the enantioselective acylation of secondary alcohols.
Efficient organocatalytic transformations that are catalyzed
by small organic molecules have been intensely investigated
in the past few years.1 In this area, thiazolium salts and
triazolium salts have long been known to catalyze the benzoin
condensation2 and the Stetter reaction3 under basic conditions,
and a number of asymmetric variants of these reactions have
been developed recently.1d In these transformations, actual
species as active catalysts are proposed to be nucleophilic
heterocyclic carbenes which are generated by the deproto-
nation of thiazolium salts or triazolium salts. On the other
hand, nucleophilic N-heterocyclic carbenes prepared from
imidazolium salts are used mainly in transition metal-
catalyzed reactions as ligands,4,5 and only a few organocata-
lytic transformations with such carbenes have been reported
to date.6-8 Although Hedrick and Nolan independently found
that the nonchiral nucleophilic N-heterocyclic carbenes
generated from imidazolium salts could catalyze transesteri-
fication reaction between esters and alcohols,6,9 there have
been only a few reports on the application of the chiral
(4) For reviews, see: (a) Herrmann, W. A.; Ofele, K.; von Preysing, D.;
Schneider, S. K. J. Organomet. Chem. 2003, 687, 229. (b) Yong, B. S.;
Nolan, S. P. Chemtracts 2003, 16, 205.
(5) Chiral imidazolium salts 1 and 2 can be readily prepared from
commercially available chiral amines 3 and 4 according to the reported
procedure, See: (a) Herrmann, W. A.; Goossen, L. J.; Artus, G. R.; Kocher,
C. Organometallics 1997, 16, 2472. (b) Sato, Y.; Yoshino, T.; Mori, M.
Org. Lett. 2003, 5, 31. (c) Alexakis, A.; Winn, C. L.; Guillen, F.; Pytkowicz,
J.; Roland, S.; Mangeney, P. AdV. Synth. Catal. 2003, 345, 345.
(6) (a) Connor, E. F.; Nyce, G. W.; Myers, M.; Mo¨ck, A.; Hedrick, J. L.
J. Am. Chem. Soc. 2002, 124, 914. (b) Grasa, G. A.; Kissling, R. M.; Nolan,
S. P. Org. Lett. 2002, 4, 3583. (c) Nyce, G. W.; Lamboy, J. A.; Connor, E.
F.; Waymouth, R. M.; Hedrick, J. L. Org. Lett. 2002, 4, 3587. (d) Grasa,
G. A.; Gu¨veli, T.; Singh, R.; Nolan, S. P. J. Org. Chem. 2003, 68, 2812.
(e) Singh, R.; Kissling, R. M.; Letellier, M.-A.; Nolan, S. P. J. Org. Chem.
2004, 69, 209. (f) Grasa, G. A.; Singh, R.; Nolan, S. P. Synthesis 2004,
971.
(7) N-heterocyclic carbene-catalyzed direct annulations of enals and
aldehydes: (a) Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem. Soc.
2004, 126, 14370. (b) Burstein, C.; Glorius, F. Angew. Chem., Int. Ed. 2004,
43, 6205.
(8) Suzuki, Y.; Toyota, T.; Imada, F.; Sato, M.; Miyashita, A. Chem.
Commun. 2003, 1314.
(1) For reviews, see: (a) Dalko, P. I.; Moisan, L. Angew. Chem., Int.
Ed. 2001, 40, 3727. (b) Jarvo, E. R.; Miller, S. J. Tetrahedron 2002, 58,
2481. (c) France, S.; Guerin, D. J.; Miller, S. J.; Lectka, T. Chem. ReV.
2003, 103, 2985. (d) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37,
534. (e) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138.
(2) (a) Sheehan, J. C.; Hara, T. J. Org. Chem. 1974, 39, 1196. (b) Tagaki,
W.; Tamura, Y.; Yano, Y. Bull. Chem. Soc. Jpn. 1980, 53, 478. (c) Zhao,
C.; Chen, S.; Wu, P.; Wen, Z. Huaxue Xuebao 1988, 46, 784. (d) Mart´ı, J.;
Castells, J.; Lo´pez-Calahorra, F. Tetrahedron Lett. 1993, 34, 521. (e) Enders,
D.; Breuer, K.; Teles, J. H. HelV. Chim. Acta 1996, 79, 1217. (f) Gerhard,
A. U.; Leeper, F. J. Tetrahedron Lett. 1997, 38, 3615. (g) Dvorak, C. A.;
Rawal, V. H. Tetrahedron Lett. 1998, 39, 2925. (h) Knight, R. L.; Leeper,
F. J. J. Chem. Soc., Perkin Trans. 1 1998, 1891. (i) Enders, D.; Kallfass,
U. Angew. Chem., Int. Ed. 2002, 41, 1743.
(3) (a) Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H. HelV. Chim. Acta
1996, 79, 1899. (b) Kerr, M. S.; Read de Alaniz, J.; Rovis, T. J. Am. Chem.
Soc. 2002, 124, 10298. (c) Kerr, M. S.; Rovis, T. Synlett 2003, 1934. (d)
Kerr, M. S.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 8876.
10.1021/ol050174r CCC: $30.25
© 2005 American Chemical Society
Published on Web 03/09/2005