COMMUNICATION
DOI: 10.1002/asia.201200076
N-Heterocyclic Carbene-Catalyzed Aerobic Oxidative Direct Esterification
of Aldehydes with Organoboronic Acids
Jing-Jing Meng, Min Gao, Yu-Ping Wei,* and Wen-Qin Zhang[a]
The ubiquitous nature of the ester functionality in the
structures of natural and synthetic molecules makes esterifi-
cation reactions very important. Numerous methods are
available for this transformation, such as nucleophilic reac-
tions of carboxylic acid derivatives with alcohols or phenols,
transesterification reactions, as well as Baeyer–Villiger oxi-
dation reactions.[1] Out of those traditional protocols, an oxi-
dative esterification of aldehydes catalyzed by N-heterocy-
clic carbenes (NHCs) is beginning to emerge as a powerful
method in organic synthesis nowadays.[2]
tion between arylboronic acids and aldehydes has been re-
ported herein. This reaction proceeded rapidly and provided
rate accelerations of up to 48-fold over Anandꢀs protocol.
Moreover, to understand this process, a mechanism involv-
ing a nucleophilic substitution reaction between B(OR)3 and
an acyl azolium species has been proposed.
We used anisaldehyde (0.37 mmol) and phenylboronic
acid (0.25 mmol) in the presence of saturated imidazolium
1 in benzene (Table 1) as the initial reaction model. As
a result, the reaction was completed in 1 hour and gave 3aa
in 42% isolated yield (Table 1, entry 1). Next, to optimize
the reaction conditions, several variables such as, solvent,
base, catalyst/base ratios, and reaction temperatures were in-
vestigated. Notably, in dimethyl sulfoxide (DMSO), the re-
action gave the target product 3aa in 67% isolated yield
after 0.5 hours at 808C under air (Table 1, entry 9). The se-
lection of the base plays a pivotal role in the reaction effi-
NHCs, first isolated by Arduengo in 1991,[3] have been
indeed widely used as versatile ligands in transition-metal
catalysis[4] and organocatalysts[5] in organic synthesis. As it is
well documented, the esterification of aldehydes is complet-
ed via the active Breslow intermediate, resulting from an in-
ternal redox reaction[6] or an external oxidation process.[7]
Recently, NHC-catalyzed esterification reactions of alde-
hydes with several nucleophillic reagents, such as hydroxy
compounds,[6a,b] aziridines,[8] and alkyl halides,[9] were report-
ed. In particular, for boronic acids several related prece-
dents were established. In 2008, Cheng et al. reported an ar-
omatic esterification reaction of aldehydes and arylboronic
acids with 5.0 mol% of a palladium–NHC complex at 1208C
under air, which tolerated many functional groups and gave
aryl benzoate derivatives with modest yields.[10] Later, Gois
et al. improved the process by using 20.0 mol% of iron–
NHC complexes, where equimolar amounts of the aldehyde
and the boronic acid gave benzoates in yields up to 97% at
908C after 24 hours.[11] However, these results indicated that
those procedures are remarkably dependent on the metal
components. Most recently, Anand and co-workers reported
an identical NHC-catalyzed reaction, which furnished prod-
ucts in up to 99% isolated yields, and proposed a concerted
mechanism.[12] However, further investigations into this pro-
tocol disclosed that long reaction times and elevated tem-
peratures (i.e., 24 h at 608C) were often required. To ad-
dress this problem, an optimized NHC-catalyzed esterifica-
ciency. DiazabicycloACHTUNRGTNE[NUG 5.4.0]undecene (DBU) was superior to
anionic oxygen bases such as K2CO3, Na2CO3, K3PO4, and
KF (Table 1, compare entry 9 with entries 10, 11, 13, and
17).[13] The stronger base, tBuOK, and the weaker organic
bases, triethylamine (TEA) and pyridine (Py), turned out to
be ineffective (Table 1; entries 14–16). The 1/base ratio also
affected the results and a ratio of 20:200 gave the best re-
sults, furnishing the product 3aa in 77% isolated yield
(Table 1; entry 21). A higher (Table 1, entry 20) or lower
(Table 1, entries 18 and 19) 1/base ratio is unfavorable for
enhancing the yield of 3aa. The screening of different
NHCs indicated that catalysts 3–7 were ineffective (Table 1,
entry 22). However, catalyst 2 (Table 1, entry 23), which is
analogous to 1, produced 3aa albeit in a diminished yield
(66%). The fine tuning of the proportions of anisaldehyde
and phenylboronic acid also greatly improved the yield of
3aa and a 2:1 ratio gave an isolated yield of 99% (Table 1,
entry 25).[14] A lower 1/base ratio (10:200) required up to
6 hours for completion and afforded 3aa in 89% yield
(Table 1, entry 27). Decreasing the temperature resulted in
no product formation, whereas elevating the temperature
did not significantly affect the efficiency (Table 1, entries 28
and 29). Therefore, the optimized conditions were deter-
mined to be: phenylboronic acid (0.25 mmol), anisaldehyde
(0.5 mmol), DBU (0.5 mmol), catalyst 1 (0.05 mmol) in
DMSO (4 mL) at 808C for about 30 min under air. Once
the optimal reaction conditions had been established, vari-
ous arylboronic acids were employed to evaluate the gener-
ality of this method. As shown in Table 2, reactions between
[a] Dr. J.-J. Meng, M. Gao, Y.-P. Wei, Prof. W.-Q. Zhang
Department of Chemistry
School of Science Tianjin University
No. 92, Weijin Road, Nan kai District, Tianjin, 300072 (China)
Fax : (+86)22-27403475
Supporting information for this article is available on the WWW
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Chem. Asian J. 2012, 7, 872 – 875