Angewandte
Chemie
DOI: 10.1002/anie.201406765
Synthetic Methods
Synthesis of a-Aryl Esters and Nitriles: Deaminative Coupling of a-
Aminoesters and a-Aminoacetonitriles with Arylboronic Acids**
Guojiao Wu, Yifan Deng, Chaoqiang Wu, Yan Zhang, and Jianbo Wang*
Abstract: Transition-metal-free synthesis of a-aryl esters and
nitriles using arylboronic acids with a-aminoesters and a-
aminoacetonitriles, respectively, as the starting materials has
been developed. The reaction represents a rare case of
Alternatively, the synthesis of a-aryl esters and nitriles can
be achieved through a cross-coupling reaction of arylboron
reagents with a-halocarbonyl compounds[14] and a-haloni-
triles,[15] respectively (Scheme 1b). Recently, Liu and co-
workers developed a palladium-catalyzed decarboxylative
coupling to access a-aryl esters and nitriles,[16] and similar
reactions have also been reported by the groups of Kwong[17]
and Xu[18] (Scheme 1c). Although significant progress has
been made in transition-metal-catalyzed synthesis of a-aryl
esters and nitriles, further development of alternative
approaches toward these important compounds is still
highly desirable.
Herein, we report a transtion-metal-free process to
synthesize a-aryl esters and nitriles by deaminative coupling
of a-aminoesters and a-aminoacetonitriles, respectively, with
boronic acids (Scheme 2). a-Aminoesters and a-aminoaceto-
nitriles attracted our attention because of their ready avail-
ability.[19] We previously reported the transtion-metal-free
reaction of boronic acids with diazo compounds.[20,21] This
type of transformation follows a simple process involving the
coordination of electron-rich diazo carbon atoms to the
electron-deficient boron center and subsequent 1,2-shift to
form a carbon–carbon bond.[22] As shown in Scheme 2, with
electron-withdrawing groups adjacent to the amino group, the
a-aminoesters and a-aminonitriles can be converted into the
3
3
2
À
À
converting C(sp ) N bonds into C(sp ) C(sp ) bonds. The
reaction conditions are mild, demonstrate good functional-
group tolerance, and can be scaled up.
N
itriles and a-aryl esters are versatile intermediates
because of their easy conversion into amides, carboxylic
acids, aldehydes, and primary amines, as well as their
applications in the synthesis of heterocyles.[1] Additionally,
a-aryl carboxylic acid derivatives are found as important
moieties in various medicinal and natural products.[2] Because
of their importance, the synthesis of a-aryl esters and nitriles
have attracted attention over the past decades.[3] Traditional
strategies for the synthesis of a-aryl nitriles include Friedel–
Crafts reactions,[4] cyanation of benzylic alcohols or halides,[5]
and dehydration of a-aryl amides and oximes.[6] These
traditional methods generally suffer from drawbacks which
include the need for toxic reagents, harsh reaction conditions,
and multistep operations.[7]
In 1997 the groups of Miura, Buchwald, and Hartwig
reported the palladium-catalyzed arylation of ketones.[8]
Subsequently, the synthesis of a-aryl esters and nitriles
through palladium-catalyzed coupling reactions was devel-
oped (Scheme 1a).[3,9] Such coupling reactions require strong
base, such as LiHMDS or NaHMDS, to deprotonate the
substrate to generate enolates. The use of strong base imposes
some limits to the reaction, including the functional-group
tolerance, side reactions from Claisen condensations, and
diarylations. To obviate the need for a strong base, zinc
enolates and silyl enol ethers,[10–12] and a-silyl nitriles and zinc
cyanoalkyls[13] have been used as the enolate precursors to
achieve arylation under mild reaction conditions.
Scheme 1. Synthesis of a-aryl esters and nitriles through transition-
metal-catalyzed coupling reactions. Tf=trifluoromethanesulfonyl.
[*] G. Wu, Y. Deng,[+] C. Wu,[+] Dr. Y. Zhang, Prof. Dr. J. Wang
Beijing National Laboratory of Molecular Sciences (BNLMS) and
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry, Peking University
Beijing 100871 (China)
E-mail: wangjb@pku.edu.cn
Prof. Dr. J. Wang
The State Key Laboratory of Organometallic Chemistry
Chinese Academy of Sciences, Shanghai 200032 (China)
[+] These authors contributed equally to this work.
[**] The project is supported by the 973 Program (No. 2012CB821600)
and NSFC (Grant Nos. 21272010 and 21332002).
Supporting information for this article is available on the WWW
Scheme 2. Transition-metal-free process for the synthesis of a-aryl
esters and nitriles.
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!