friendly solution that could be carried out under mild
reaction conditions.
Tr a n sester ifica tion /Acyla tion of Secon d a r y
Alcoh ols Med ia ted by N-Heter ocyclic
Ca r ben e Ca ta lysts
The N-heterocyclic carbenes (NHC) have been shown
to act as excellent phosphine mimics.9 Not only do they
possess comparable or better donating properties9,12c than
most phosphines, but NHCs are neither toxic nor pyro-
phoric. NHCs were first discovered by Wanzlick10 in the
1960s, while the isolation and utilization of stable NHCs
by Arduengo occurred some 20 years later.11 In terms of
reactivity, NHCs behave as nucleophiles owing to their
lone electron pair.12 The versatility of NHCs has been
established in reports demonstrating their role as ef-
ficient catalysts in the ring-opening polymerization of
lactones,13 in mediating the benzoin condensation,14 and
in multicomponent reactions.15 Recent work has estab-
lished the vast scope of NHCs and their derivatives in
terms of their stabilizing effect in organometallic sys-
tems.16
Rohit Singh, Rebecca M. Kissling,
Marie-Anne Letellier,† and Steven P. Nolan*
Department of Chemistry, University of New Orleans,
New Orleans, Louisiana 7014
snolan@uno.edu
Received September 30, 2003
Abstr a ct: N-Heterocyclic carbenes (NHC) are efficient
catalysts for transesterification/acylation reactions involving
secondary alcohols. The catalytic transformations are carried
out employing low catalyst loadings in convenient reaction
times at room temperature.
We and the Hedrick group, simultaneously, reported
the use of various alkyl- and aryl-substituted imidazol-
2-ylidene carbenes as efficient transesterification/acyla-
tion reaction catalysts.17 Here, we wish to report the use
of the same imidazolium-based system for the transes-
terification/acylation of a variety of secondary alcohols,
further establishing the versatility and utility of NHCs
for such transformations.
The acylation of commercially available alcohols with
varied electronic and steric properties was carried out
using a simple protocol (Table 1). All entries in Table 1
reached completion in 1 h, and reported isolated yields
are for reactions reaching complete conversion. The
reaction of 2-propanol with methyl acetate yields the
The ester moiety is a common functional group in
polymers, drugs, and biologically relevant compounds. In
addition, the ester functionality serves as a protecting
group for alcohols.1 Preparation of esters may be achieved
through reactions of alcohols with carboxylic acids or
more effectively by ester interchange2 or by transesteri-
fication,3 where generally a methyl ester reacts with an
alcohol to form a new ester and methanol.
Lewis acidic or basic catalysts have been used as either
catalysts or promoters to mediate this reaction. However,
Lewis acid catalysts2 exhibit low substrate selectivity and
can cleave sensitive functional groups such as acetals,
dienes, and epoxides. They may also lead to formation of
side products and deterioration of primary products
during the prolonged reaction times.4 Utilizing strongly
basic catalysts such as sodium hydride and potassium
tert-butoxide leads to high conversions, but the use of
such species is problematic for base-sensitive sub-
strates,2,3 while the weaker tertiary phosphine bases are
toxic and expensive. Therefore, with either acidic or basic
conditions, such transesterification reactions do not prove
to proceed efficiently under mild reaction conditions.5
(9) Green, J . C.; Scurr, R. G.; Arnold, P. L.; Cloke, G. N. Chem.
Commun. 1997, 20, 1963-1964.
(10) (a) Wanzlick, H.-W.; Schikoro, E. Angew. Chem. 1960, 72, 494.
(b) Wanzlick, H.-W. Angew. Chem. 1962, 1, 129-134. (c) Wanzlick,
H.-W.; Schonherr, H.-J . Angew. Chem. 1968, 7, 141-142. (d) Wanzlick,
H.-W.; Schonherr, H.-J . Liebigs. Ann. Chem. 1970, 731, 176-179.
(11) Arduengo, A. J ., III; Harlow, R. L.; Kline, M. K. J . Am. Chem.
Soc. 1991, 113, 361-363.
(12) For comprehensive reviews see: (a) Herrmann, W. A. Angew.
Chem., Int. Ed. 2002, 41, 1290-1309. (b) Bourissou, D.; Guerret, O.;
Gabba¨ı, F. P.; Bertrand, G. Chem. Rev. 2000, 100, 39-91. (c) Regitz,
M. Angew. Chem., Int. Ed. Engl. 1996, 35, 725-728. (d) Arduengo, A.
J ., III; Krafczyk, R. Chem. Z. 1998, 32, 6-14.
6
Organometallic catalysts such as Cp*2Sm(thf)2 and
distannoxanes,7 or the basic iminophosphoranes8 require
high catalyst loadings and long reaction times to achieve
this transformation. There have been continued efforts
to find efficient metal-free catalysts to mediate this
transformation in order to provide an environmentally
(13) Connor, E. F.; Nyce, G. W.; Meyers, M.; Mock, A.; Hedrick, J .
L. J . Am. Chem. Soc. 2002, 124, 914-915.
(14) (a) Enders, D.; Kallfass, U. Angew. Chem., Int. Ed. 2002, 41,
1743-1745. (b) Kerr, M. S.; Read de Alaniz, J .; Rovis, T. J . Am. Chem.
Soc. 2002, 124, 10298-10299.
(15) Nair, V.; Bindu, S.; Sreekumar, V.; Rath, N. P. Org. Lett. 2003,
5, 665-667.
* Corresponding author.
(16) (a) Ref 12. (b) Bohm, V. P. W.; Gstottmayr, C. W. K.; Weskamp,
T.; Herrmann, W. A. J . Organomet. Chem. 2000, 595, 186-190. (c)
Huang, J .; Schanz, H.-J .; Stevens, E. D.; Nolan, S. P. Organometallics
1999, 18, 2370-2375. (d) Huang, J .; Stevens, E. D.; Nolan, S. P.;
Petersen, J . L. J . Am. Chem. Soc. 1999, 121, 2674-2678. (e) Stauffer,
S. R.; Lee, S.; Stambuli, J . P.; Hauck, S. I.; Hartwig, J . F. Org. Lett.
2000, 2, 1423-1426. (f) Scholl, M.; Trnka, T. M.; Morgan, J . P.; Grubbs,
R. H. Tetrahedron Lett. 1999, 40, 2247-2250. (g) Weskamp, T.;
Schattenmann, W. C.; Spiegler, M.; Herrmann, W. A. Angew. Chem.,
Int. Ed. 1998, 37, 2490-2493. (h) Littke, A. F.; Fu, G. C. Angew. Chem.,
Int. Ed. 2002, 41, 4176-4211.
† Visiting student from the Universite´ Pierre et Marie Curie, Paris,
France.
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Chemistry; J ohn Wiley and Sons Inc.: New York, 1991.
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(3) Otera, J . Chem. Rev. 1993, 93, 1449-1470.
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(17) (a) Grasa, G. A.; Kissling, R. M.; Nolan, S. P Org. Lett. 2002, 4,
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10.1021/jo035431p CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/05/2003
J . Org. Chem. 2004, 69, 209-212
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