A General and mild catalytic α-alkylation of unactivated esters using Alcohols

Article abstract of DOI:10.1002/anie.201410293

Catalytic α-alkylation of esters with primary alcohols is a desirable process because it uses low-toxicity agents and generates water as the by-product. Reported herein is a NCP pincer/Ir catalyst which is highly efficient for α-alkylation of a broad scope of unactivated esters under mild reaction conditions. For the first time, alcohols alkylate unactivated α-substituted acyclic esters, lactones, and even methyl and ethyl acetates. This method can be applied to the synthesis of carboxylic acid derivatives with diverse structures and functional groups, some of which would be impossible to access by conventional enolate alkylations with alkyl halides. In a pinch: An NCP pincer/iridium catalyst is highly efficient for the α-alkylation of unactivated esters using alcohol under mild reaction conditions. The reaction is simple, clean, and scalable (1-10 mmol), and the scope with respect to the ester is wide.

Full text of DOI:10.1002/anie.201410293

Angewandte
Chemie
DOI: 10.1002/anie.201410293
Homogeneous Catalysis
A General and Mild Catalytic a-Alkylation of Unactivated Esters
Using Alcohols**
Le Guo, Xiaochen Ma, Huaquan Fang, Xiangqing Jia, and Zheng Huang*
Abstract: Catalytic a-alkylation of esters with primary alco-
hols is a desirable process because it uses low-toxicity agents
and generates water as the by-product. Reported herein is
a NCP pincer/Ir catalyst which is highly efficient for a-
alkylation of a broad scope of unactivated esters under mild
reaction conditions. For the first time, alcohols alkylate
unactivated a-substituted acyclic esters, lactones, and even
methyl and ethyl acetates. This method can be applied to the
synthesis of carboxylic acid derivatives with diverse structures
and functional groups, some of which would be impossible to
access by conventional enolate alkylations with alkyl halides.
peting side reactions, such as enolate eliminations and Claisen
condensations, restrict the substrate scope (e.g., the enolates
derived from methyl and ethyl acetates undergo self-con-
densations readily); and 3) the prerequisite formation of ester
enolates typically requires harsh reaction conditions (super-
base and low temperature).[1]
An alternative, but less developed method for a-alkyla-
tion of carbonyl compounds is to use alcohols as the alkylating
agents. Industrially, alcohols are preferred reagents because
they are more environmentally benign and less expensive
than alkyl halides. Moreover, alkylations with alcohols form
water as the only by-product. Over the last decade, alkyla-
tions with primary alcohols using the “borrowing hydrogen”
a-Alkylation of esters is one of the most fundamental
processes for carbon–carbon bond formation.[1] The classical
methods, enolate alkylations, involve the deprotonation of the
esters and the addition of the resulting enolate nucleophiles to
alkyl halide electrophiles (Figure 1a).[2] The noncatalytic SN2
substitution reactions are presented in every introductory
organic chemistry course. However, such methods have
several crucial limitations: 1) the use of toxic alkylating
agents and the formation of inorganic salts as waste; 2) com-
methodology have emerged as powerful and green processes
[3]
À
À
for C C and C N bond formations. Well-developed reac-
tions include N-alkylations of amines and sulfonamides,[3g,4] b-
alkylations of alcohols (Guerbet reactions),[5] a-alkylation of
ketones,[6] etc.[7]
The a-alkylation of unactivated ester with primary
alcohols, however, has remained a challenging and significant
goal. Recently, the group of Ishii reported the only examples
of a-alkylation of unactivated ester with alcohols.[8] The
reactions occurred at 1008C in tBuOH with a combination of
5 mol% [{Ir(cod)Cl}2] and 15 mol% PPh3 in the precense of
2 equivalents of KOtBu. The work represents a breakthrough
in catalytic ester alkylations, but is restricted to reactions with
tert-butyl acetate, and a large excess of this ester (10 equiv
relative to alcohol) was required.[8] tert-Butyl acetate is
relatively easy for alkylation compared to other acetates
containing smaller substituents.[1a] To the best of our knowl-
edge, however, no catalyst systems have been reported for a-
alkylations of unactivated esters other than that of tert-butyl
acetate with alcohols.[9]
Herein we demonstrate that a pincer NCP/Ir catalyst is
remarkably active for ester alkylation with primary alcohols.
Most reactions proceeded to high conversion under mild
reaction conditions using very low catalyst loading with
alcohol to ester ratios of about 1:1 (Figure 1b). More
importantly, the protocol enables the alkylation of a wide
range of esters including challenging substrates such as ethyl
and methyl acetates and a-substituted esters. Furthermore,
the alkylation of g-substituted g-butyrolactones provides cis
a,g-disubstituted isomers which cannot be accessed by con-
ventional means.
Figure 1. Classical method (a) and catalytic method (b) for a-alkyla-
tions of esters.
[*] L. Guo, X. Ma, H. Fang, X. Jia, Prof. Dr. Z. Huang
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
345 Lingling Road, Shanghai 200032 (China)
E-mail: huangzh@sioc.ac.cn
We commenced by investigating iridium catalysts for
alkylation of tert-butyl acetate (2a) with benzylalcohol (1a).
Previous work in our group showed that a PN3P pincer/Ir
complex (5; see Table 1) catalyzes a-alkylation of unactivated
secondary and tertiary acetamides with alcohols.[10] We
envisioned that pincer/Ir complexes with high thermal
[**] We gratefully acknowledge the financial support from the National
Natural Sciences Foundation of China (No. 21422209, 21432011),
and the Science and Technology Commission of Shanghai Munic-
ipality (No. 13A1404200, 13JC1406900).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201410293.
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
stability might be also effective for a-alkylation of unacti-
vated esters. In a preliminary experiment, a 1:10 molar ratio
of 1a/2a, identical to that reported in previous study, was
used.[8] Although the use of tBuOH as a solvent would have
a beneficial effect on the reaction with tert-butyl acetate,[8] the
ester exchange involving the solvent would limit the scope of
the ester to tert-butyl esters. With toluene as a solvent, the
reaction of 1a with 10 equivalents of 2a in the presence of
2 mol% of 5 and 2 equivalents of KOtBu gave the alkylation
product 3a in only 25% yield after 12 hours at 1108C. The
ester interchange between 1a and 2a formed 55% of the
benzyl ester 4 as the side product (entry 1, Table 1). The
to be studied, the replacement of one bulky di-tert-butyl
phosphinite group in 6 with a pyridine moiety creats a steri-
cally less demanding coordination environment around the
iridium center.[13] To our delight, the reaction using 9 at 1108C
gave 3a in 95% yield, and no ester-exchange product (4) was
observed (entry 5). The high activity of 9 allowed this
transformation to occur at 608C, thus furnishing 3a in 99%
yield after 12 h (entry 6).
A practical catalytic alkylation should avoid using esters
in large excess. With the remarkably active catalyst, we found
that the reaction of 1a with 2a in a 1:1.2 ratio using only
0.5 mol% of 9 occurred at 608C in high yield (Table , entry 7).
The run with a lower catalyst loading (0.1 mol%) could still
afford 3a in 68% yield (entry 8). The reactions proceeded
even at room temperature, thus giving 3a in 86% yield after
3 days (entry 9). Our catalyst system is robust towards air and
moisture. The reaction in the presence of air and using
reagents and solvent without dyring occurred smoothly at
608C (entry 10). Thus, the transformation can be performed
without the need of a drybox, and allows the non-expert to
fully utilize this methodology.
Table 1: Evaluation of iridium catalysts for a-alkylation of tert-butyl
acetate (1a) with benzylalcohol (2a).[a]
Entry
Cat.
2a
KOtBu
T [8C]
Yield [%][b]
(mol%)
(equiv)
(equiv)
3a
4
Using the very active NCP/Ir catalyst and optimal
reaction conditions (entry 7, Table 1), the scope of the
reaction was investigated by variying the primary alcohol
(Scheme 1) and ester (Scheme 2). Benzylic alcohols contain-
1
2
3
4
5
6
7
8
5 (2)
6 (2)
7 (2)
8 (2)
9 (2)
9 (2)
9 (0.5)
9 (0.1)
9 (0.5)
9 (0.5)
10
10
10
10
10
10
1.2
1.2
1.2
1.2
2
2
2
2
2
2
1.5
1.5
1.5
1.5
110
110
110
110
110
60
60
60
23
60
25
41
45
78
95
99
89 (87)
68
86
55
39
40
19
–
–
–
18
9
11
9[c]
10[d]
72
[a] Reaction conditions: Ir complex (0.1–2 mol%) in 1.0 mL of toluene
with 1a (1 mmol), 2a (1.2–10 equiv), and KOtBu (1.5–2 equiv) at 60 or
1108C for 12 h. [b] Yields were determined by 1H NMR spectroscopy with
mesitylene as an internal standard. Value within parentheses is the yield
of the isolated product. [c] At 238C for 3 days. [d] Reagents and solvent
were used without drying, and manipulations were carried out under air.
reactions using a related POCOP pincer complex (6) and the
PCP pincer complex 7[11] (2 mol% each) gave 3a in 41 and
45% yields, respectively, but a decent amount of 4 was still
observed (entries 2 and 3). The results indicate that the facile
ester exchange is the main factor causing low conversion to
the alkylation product.[12] To compete with this side reaction,
the rate of iridium-catalyzed alcohol dehydrogenation to an
aldehyde must be enhanced. A decrease in the steric bulk
(tBu groups in 7) to the analogous complex 8 with iPr groups
led to an improved yield of 3a (78%)(entry 4), thus suggest-
ing that a less sterically hindered ligand is important for
generating a more active catalyst. To this end, we investigated
the NCP/Ir complex 9. Though the electronic difference
between the NCP and the classic PCP/Ir complexes remains
Scheme 1. NCP/Ir-catalyzed a-alkylation of tert-butyl acetate (2a) with
various primary alcohols. Yields shown are of isolated products.
ing both electron-donating and electron-withdrawing groups
alkylated 2a efficiently (Scheme 1). A methyl group at all the
positions on the aromatic ring was tolerated (3b–d). Benzylic
alcohols containing para-fluoro, para-chloro, and para-bromo
substituents were compatible (3 f–h). No protodehalogena-
tion products were detected under the reaction conditions.
Heterocyclic alcohols, such as 2-furanmethanol (1j) and 1,3-
benzodioxole-5-methanol (1k) reacted smoothly. Further-
2
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Scheme 2. NCP/Ir-catalyzed a-alkylation of various esters with alco-
hols. Yields shown are those of isolated products. [a] Ester/alco-
hol=1.2:1. [b] Ester/alcohol=3:1. [c] In neat, ester/alcohol=8:1.
Scheme 3. NCP/Ir-catalyzed a-alkylation of lactones with alcohols.
Yields shown are those of isolated products. [a] Isolated as a mixture
of cis and trans isomers.
more, the couplings of nonbenzylic primary alcohols (1m–q)
and 2a formed the desired products 3m–q in useful yields.
More importantly, our catalyst system allows, for the first
time, the a-alkylation of unactivated a-substituted esters with
primary alcohols. These reactions significantly broaden the
synthetic utility of this methodology. As shown in Scheme 2,
the reactions of tert-butyl propionate, tert-butyl caproate, and
tert-butyl valerate with primary alcohols in 1:1.2 ratios
occurred in high yields (10a–d). It is well known that a-
alkylation of acetates with smaller substituents is more
challenging than that with tert-butyl acetate.[1a] Excitingly,
acetates with various substituents, such as n-hexyl, cyclohexyl,
benzyl, and 2-ethoxyethyl groups, underwent alkylation
smoothly (10e–k), albeit with a relatively high ester to
alcohol ratio (3:1). Such reactions constitute the first catalytic
a-alkylation of unactivated acetates other than tert-butyl
acetate.
Ethyl acetate is manufactured on a tremendous scale in
industry for use as a low toxicity solvent. Therefore, the a-
alkylation of ethyl acetate is of special interest. However, the
noncatalyzed alkylation of ethyl acetate with alkyl halides is
a problem because of side reactions such as the Claisen
condensation.[14] Significantly, the iridium-catalyzed reactions
of ethyl acetate with alcohols on a 10 mmol scale in neat
(alcohol/acetate 1:8) afforded the ethyl esters 10l–n in good
yields. The most challenging substrate, methyl acetate, was
alkylated on gram-scale in the same vein (10o and 10p). Note
that the unreacted volatile acetates could be easily separated
from the products through distillation and reused thereafter.
Thus, the protocol provides a simple and clean approach to
ethyl and methyl esters by utilizing the low-cost, low-toxicity,
and readily accessible acetate sources.
The successful a-alkylation of a-substituted acyclic esters
(10a–d; Scheme 2) inspired us to develop procedures for
catalytic the a-alkylation of lactones. As summarized in
Scheme 3, the reactions of the g-butyrolactone (11a;
1.2 equiv) with 1a in the presence of 0.5 mol% 9 and
2 equivalents LiOtBu at 608C afforded the a-alkylation
product 12a in 72% yield.[15] d-Valerolactone (11b) and
dihydrocoumarin (11c), which have six-membered rings, also
underwent a-alkylation smoothly. The alkylation of (R,S)-d-
octalactone (11d) with 1a gives a 40:60 mixture of the cis and
trans diastereomers. The reaction of (R,S)-g-phenyl-g-butyr-
olactone (11e) formed 12e with a 70:30 d.r. Of significance is
the isolation of the cis a,g-disubstituted g-butyrolactone
(52% isolated yield) as the major product because the cis
isomer cannot be prepared by traditional enolate alkylation
with an alkyl halide.[16] For instance, the alkylation of 11e with
benzyl bromide and LDA at À788C formed the thermody-
namically more stable trans isomer exclusively.
A range of benzylic and nonbenzylic alcohols reacted with
g-butyrolactones to give the cis products diastereoselectively
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
(12 f–n; Scheme 3). The incorporation of an ortho substituent
on the benzylalcohols leads to enhanced selectively (81:19 d.r.
for 12g and 12h). The size of the substitutents at the
g position of the g-butyrolactones has a minor impact on the
selectivity (70:30 for 12e versus 64:36 for 12m, and 72:28 for
12n). Although the diastereoselectivity is moderate (up to
81:19 d.r.), this is an effective asymmetric method for the
synthesis of cis a,g-disubstituted butyrolactones.
We attribute the preference for the formation of the
cis diastereomers to the iridium-catalyzed asymmetric hydro-
genation of a,b-unsaturated carbonyl intermediate with
diastereotopic faces. The iridium center would preferably
attack the less sterically demanding face (trans to the g-
substituent), and the subsequent addition of hydrogen to the
C–C double bond in a cis fashion leads to the formation of the
cis products.
Finally, the method was applied to a convenient synthesis
of an important anticonvulsant drug, valoproic acid (13). The
current synthesis of 13 begins with the dialkylation of
cyanoacetate with mutagenic n-propyl bromide, followed by
a multiple-step hydrolysis and decarboxylation (at 140–
1908C) sequence (Scheme 4).[17] The process gives a signifi-
cant amount of inorganic salts as by-products. By comparison,
[1] a) F. A. Carey, R. K. Sundberg in Advanced Organic Chemistry,
5th ed., Part B, Springer, Heidelberg, 2007, pp. 1 – 31; b) J. Hoyle
in The Chemistry of Acid Derivatives, Vol. 2 (Ed.: S. Patai),
Wiley, Chichester, UK, 1992, pp. 615 – 702.
[2] For examples, see: a) S. Danishefsky, K. Vaughan, R. Gadwood,
K. Tsuzuki, J. Am. Chem. Soc. 1981, 103, 4136; b) T. Ling, C.
Chowdhury, B. A. Kramer, B. G. Vong, M. A. Palladino, E. A.
Theodorakis, J. Org. Chem. 2001, 66, 8843; c) A. Zakarian, A.
Batch, R. A. Holton, J. Am. Chem. Soc. 2003, 125, 7822.
[3] For reviews, see: a) C. Gunanathan, D. Milstein, Science 2013,
341, 249; b) R. H. Crabtree, Organometallics 2011, 30, 17; c) S.
Bꢀhn, S. Imm, L. Neubert, M. Zhang, H. Neumann, M. Beller,
ChemCatChem 2011, 3, 1853; d) T. Suzuki, Chem. Rev. 2011, 111,
1825; e) Y. Obora, Y. Ishii, Synlett 2011, 30; f) O. Saidi, J. M. J.
Williams, Iridium Catal. 2011, 34, 77; g) A. J. A. Watson, J. M. J.
Williams, Science 2010, 329, 635; h) G. Guillena, D. J. Ramꢁn, M.
Yus, Chem. Rev. 2010, 110, 1611; i) G. E. Dobereiner, R. H.
Crabtree, Chem. Rev. 2010, 110, 681; j) K.-i. Fujita, R. Yama-
guchi, Synlett 2005, 560.
[4] For examples, see: a) C. Gunanathan, D. Milstein, Angew. Chem.
Int. Ed. 2008, 47, 8661; Angew. Chem. 2008, 120, 8789; b) F. Shi,
M. K. Tse, S. Zhou, M.-M. Pohl, J. Radnik, S. Hꢂbner, K.
Jꢀhnisch, A. Brꢂckner, M. Beller, J. Am. Chem. Soc. 2009, 131,
1775; c) M. H. S. A. Hamid, C. L. Allen, G. W. Lamb, A. C.
Maxwell, H. C. Maytum, A. J. A. Watson, J. M. J. Williams, J.
Am. Chem. Soc. 2009, 131, 1766; d) S. Michlik, R. Kempe, Chem.
Eur. J. 2010, 16, 13193.
[5] For examples, see: a) C. S. Cho, B. T. Kim, H.-S. Kim, T.-J. Kim,
S. C. Shim, Organometallics 2003, 22, 3608; b) T. Matsu-ura, S.
Sakaguchi, Y. Obora, Y. Ishii, J. Org. Chem. 2006, 71, 8306; c) R.
Martꢃnez, D. J. Ramꢁn, M. Yus, Tetrahedron 2006, 62, 8982;
d) L. J. Allen, R. H. Crabtree, Green Chem. 2010, 12, 1362.
[6] For examples, see: a) C. S. Cho, B. T. Kim, T.-J. Kim, S. C. Shim,
Tetrahedron Lett. 2002, 43, 7987; b) K. Taguchi, H. Nakagawa, T.
Hirabayashi, S. Sakaguchi, Y. Ishii, J. Am. Chem. Soc. 2004, 126,
72; c) T. Kuwahara, T. Fukuyama, I. Ryu, Org. Lett. 2012, 14,
4703; d) M. L. Buil, M. A. Esteruelas, J. Herrero, S. Izquierdo,
I. M. Pastor, M. Yus, ACS Catal. 2013, 3, 2072; e) Q. Xu, J. Chen,
H. Tian, X. Yuan, S. Li, C. Zhou, J. Liu, Angew. Chem. Int. Ed.
2014, 53, 225; Angew. Chem. 2014, 126, 229; f) L. K. M. Chan,
D. L. Poole, D. Shen, M. P. Healy, T. J. Donohoe, Angew. Chem.
Int. Ed. 2014, 53, 761; Angew. Chem. 2014, 126, 780; g) S. Ogawa,
Y. Obora, Chem. Commun. 2014, 50, 2491.
Scheme 4. Catalytic and classical methods for synthesis of valoproic
acid (13).
the catalytic method reported herein allows a short, mild, and
clean synthesis of 13 from inexpensive and low-toxicity
reagents. With n-propanol (8 mL) as the alkylating reagent/
solvent, the reaction of methyl valerianate (10 mmol) in the
presence of 0.5 mol% of an iridium catalyst at 608C formed
valoproic esters. Following hydrolysis, 13 was obtained on
a gram-scale in two steps and 70% overall yield (1.0 g), with
H2O and MeOH as the by-products (Scheme 4).
In summary, we have developed an effective method for
a-alkylation of unactivated esters with primary alcohols by
using an NCP/Ir pincer complex. The new method overcomes
several limitations and complements the scope of current
methods for ester alkylation. Featuring mild reaction con-
ditions, environmentally benign reagents, broad substrate
scope, good functional group compatibility, and high atom
economy with water as the by-product, this method is
a simple, practical, and green process for a-alkylation of
esters.
À
À
[7] Selected examples of other types of C C and C N bond
formations by dehydrogenative alcohol activations, see: a) L.
Shi, Y.-Q. Tu, M. Wang, F.-M. Zhang, C.-A. Fan, Y.-M. Zhao, W.-
J. Xia, J. Am. Chem. Soc. 2005, 127, 10836; b) S. Whitney, R.
Grigg, A. Derrick, A. Keep, Org. Lett. 2007, 9, 3299; c) C.
Gunanathan, Y. Ben-David, D. Milstein, Science 2007, 317, 790;
d) J. F. Bower, E. Skucas, R. L. Patman, M. J. Krische, J. Am.
Chem. Soc. 2007, 129, 15134; e) B. Blank, R. Kempe, J. Am.
Chem. Soc. 2010, 132, 924; f) S. Michlik, R. Kempe, Nat. Chem.
2013, 5, 140; g) M. Zhang, H. Neumann, M. Beller, Angew.
Chem. Int. Ed. 2013, 52, 597; Angew. Chem. 2013, 125, 625.
[8] Y. Iuchi, Y. Obora, Y. Ishii, J. Am. Chem. Soc. 2010, 132, 2536.
[9] For examples of the a-alkylation of activated esters, see: a) P. J.
Black, G. Cami-Kobeci, M. G. Edwards, P. A. Slatford, M. K.
Whittlesey, J. M. J. Williams, Org. Biomol. Chem. 2006, 4, 116;
b) M. Morita, Y. Obora, Y. Ishii, Chem. Commun. 2007, 2850;
c) R. Grigg, C. Lofberg, S. Whitney, V. Sridharan, A. Keep, A.
Derrick, Tetrahedron 2009, 65, 849.
Received: October 21, 2014
Published online: && &&, &&&&
[10] a) L. Guo, Y. Liu, W. Yao, X. Leng, Z. Huang, Org. Lett. 2013, 15,
1144. More recently, Ryu et al. reported ruthenium-catalyzed a-
alkylation of unactivated tertiary acetamides. See: b) T. Kuwa-
hara, T. Fukuyama, I. Ryu, RSC Adv. 2013, 3, 13702.
Keywords: alcohols · alkylation · homogeneous catalysis ·
.
iridium · synthetic methods
4
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
[11] These iridium pincer complexes have been well studied for
alkane hydrogenations. For a recent review, see: J. Choi,
A. H. R. MacArthur, M. Brookhart, A. S. Goldman, Chem.
Rev. 2011, 111, 1761.
[12] The ester interchange occurs in the absence of the iridium
catalyst. Under otherwise identical reactioin conditions, the
reaction without the iridium catalyst gave 4 in 24% yield after
1 h.
[14] As a comparison, the reaction of ethyl acetate with lithium
diisopropylamide and benzyl bromide at À788C gave only 17%
of the alkylation product 10l.
[15] The reaction with 2 equiv of LiOtBu provided higher yield than
that with 1.5 equiv of KOtBu (53% yield).
[16] Ghosh et al. demonstrated the selective formation of trans a,g-
disubstituted butyrolactones through alkylation with various
alkyl halides. See: A. K. Ghosh, K. Shurrush, S. Kulkarni, J. Org.
Chem. 2009, 74, 4508.
[13] We recently reported the NCP pincer/Ir complex for transfer
dehydrogenation of alkanes. See: X. Jia, L. Zhang, C. Qin, X.
Leng, Z. Huang, Chem. Commun. 2014, 50, 11056.
[17] a) M. Chignac, C. Grain, U.S. Pat. 4155929, 1979; b) H. E. J.-M.
Meunier, U.S. Pat. 3325361, 1967.
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Homogeneous Catalysis
L. Guo, X. Ma, H. Fang, X. Jia,
Z. Huang*
&&& — &&&
A General and Mild Catalytic a-Alkylation
of Unactivated Esters Using Alcohols
In a pinch: An NCP pincer/iridium cata-
lyst is highly efficient for a-alkylation of
unactivated esters using alcohol under
mild reaction conditions. The reaction is
simple, clean, and scalable (1–10 mmol),
and the scope with respect to the ester is
wide.
6
www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 1 – 6
These are not the final page numbers!