phines. Our expertise with NHC and the fact that transes-
terification of enol esters can be effected by basic tertiary
phosphines such as PBu32d or iminophosphoranes6 led us to
attempt transesterification utilizing NHC. Indeed, as little as
0.5 mol % of the NHC IMes catalyzes the reaction of benzyl
alcohol with vinyl acetate in THF, with almost quantitative
conversion to benzyl acetate in 5 min at room temperature
(Scheme 2).
Table 1. Transesterification of Methyl Acetate with Benzyl
Alcohol Catalyzed by Various Nucleophiles
entry
catalyst
yielda (%)
1
2
3
IMes
IPr
SIMes
SIPr
93
45
21
Scheme 2. IMes-Catalyzed Acylation of Benzyl Alcohol with
Vinyl Acetate
4
21
5
6
7
8
ICy
ICy
IAd
ItBu
DMAP
DABCO
DBU
NaH
KOtBu
100
84b
100
100
15
45
24
95
95
9
10
11
12
13
a GC yield, average of two runs. b Molecular sieves were not used.
On the basis of this promising result, the acylation of a
commercially available and more challenging substrate,
methyl acetate, was tested with different nucleophiles. To
the best of our knowledge, this is the first report on the use
of methyl acetate as an acylating agent. Two main factors
were identified for biasing the reaction in the desired
direction. First, 4 Å molecular sieves are required to absorb
the liberated methanol. This use leads to quantitative
conversion of benzyl alcohol to benzyl acetate in 1 h with
2.5 mol % of ICy (Table 1, entries 5 and 6). Second, the
nature of the nucleophile also influences the efficacy of
transesterification. Under similar conditions (2.5 mol %
catalyst, 1 mL of methyl acetate, 1 h, molecular sieves), IMes
afforded the product in 93% conversion, while IPr led to
only a moderate conversion (possibly due to its steric bulk)
(Table 1, entries 1 and 2). The corresponding aryl-substituted
imidazolin-2-ylidenes, SIMes and SIPr, afforded the products
in low conversion (Table 1, entries 3 and 4).10 The alkyl-
substituted ICy, ItBu, and IAd performed much better in the
model reaction affording the product quantitatively (Table
1, entries 5, 7, and 8) presumably due to their higher
nucleophilicity.9a,11
of methyl acetate with benzyl alcohol (Table 1, entries
9-11). As expected, the strong inorganic bases NaH and
KOtBu led to high conversions. However, the use of these
bases may be problematic for more sensitive substrates.1,14
Once having established that the NHC represent excellent
catalysts for the transesterification reaction of vinyl acetate/
methyl acetate with benzyl alcohol, we investigated various
substrates (Table 2). Geraniol 5 and cinnamyl alcohol 7 react
rapidly with vinyl acetate in the presence of 1 mol % IMes
to form the desired products quantitatively (Table 2, entries
1 and 2). Alcohols bearing acid-sensitive functional groups
such as 95 led to the corresponding acetate in very short
reaction times and in the presence of only 0.5 mol % catalyst
(Table 2, entry 3). Acrylic esters can be problematic
substrates for the transesterification reaction due to undesir-
able side reactions such as isomerization or polymerization.
Vinyl acrylate effectively acylated benzyl alcohol, albeit
using a higher loading of the more active catalyst ICy (Table
2, entry 12).
The scope and generality of this method was also expanded
to the readily available methyl esters. The use of methyl
acetate effected not only the transesterification of benzyl
alcohol in excellent yield (Table 2, entry 4), but also
performed well in the reaction with the acid-labile alcohol
9, affording the product 10 in 90% isolated yield (Table 2,
entry 5). Ethyl acetate, used commonly as solvent, also
underwent efficient transesterification with benzyl alcohol.
The ethyl alcohol generated in the course of the reaction
was removed from the equilibrium using 5 Å molecular
sieves (Table 2, entry 11).
Strongly basic species such as DMAP,2 DABCO,12 and
DBU13 are not effective catalysts for the transesterification
(6) Ilankumaran, P.; Verkade, J. G. J. Org. Chem. 1999, 64, 9063-9066.
(7) Ranu, B. C.; Dutta, P.; Sarkar, A. J. Org. Chem. 1998, 63, 6027-
6028.
(8) Recent related reports make use of NHC in polymerization of cyclic
esters (Connor, E. F.; Nyce, G. W.; Myers, M.; Mock, A.; Hedrick, J. L. J.
Am. Chem. Soc. 2002, 124, 914-915) and in mediating the asymmetric
benzoin condensation: Enders, D.; Kalfass, U. Angew. Chem., Int. Ed. 2002,
41, 1743-1745.
(9) (a) Huang, J.; Stevens, E. D.; Nolan, S. P.; Petersen, J. L. J. Am.
Chem. Soc. 1999, 121, 2674-2678. (b) Huang, J.; Schanz, H.-J.; Stevens,
E. D.; Nolan, S. P. Organometallics 1999, 18, 2370-2375.
(10) Arduengo, A. J., III; Calabrese, J. C.; Davidson, F.; Rasika Dias,
H. V.; Goerlich, J. R.; Krafczyk, R.; Marshall, W. J.; Tamm, M.; Schmutzler,
R. HelV. Chim. Acta 1999, 82, 2348-2364.
The deprotection of methyl esters usually requires severe
reaction conditions; therefore, their conversion to benzyl
(12) Aggrawal, V. K.; Dean, D. K.; Mereu, A.; Williams, R. J. Org.
Chem. 2002, 67, 510-514.
(13) Aggrawal, V. K.; Mereu, A. Chem. Commun. 1999, 2311-2312.
(14) Stanton, M. G.; Gagne´, M. R. J. Org. Chem. 1997, 62, 8240-8242.
(11) Kim, Y.-J.; Streitwieser, A. J. Am. Chem. Soc. 2002, 124, 5757-
5761.
3584
Org. Lett., Vol. 4, No. 21, 2002