DOI: 10.1002/chem.201103671
Oxidative Mizoroki–Heck-Type Reaction of Arylsulfonyl Hydrazides for a
Highly Regio- and Stereoselective Synthesis of Polysubstituted Alkenes
Fu-Lai Yang,[a] Xian-Tao Ma,[a] and Shi-Kai Tian*[a, b]
Stereodefined alkenes are ubiquitous structural motifs in
many biologically relevant molecules, and moreover, they
are frequently employed in a broad range of chemical trans-
formations. In addition to carbonyl olefination, elimination,
alkyne addition, and alkene metathesis, a plethora of alke-
nylation methods have been developed for stereoselective
alkene synthesis.[1] Particularly noteworthy is the Mizoroki–
Heck reaction between aryl halides and alkenes in the pres-
ence of palladium catalysts and bases to yield higher substi-
tuted alkenes.[2] Ever since its discovery in early 1970s,[3] the
Mizoroki–Heck reaction has received numerous modifica-
tions and notably, aryl halides can be replaced by a few
other types of aryl sources such as aryl sulfonates,[4] aryldia-
zonium salts,[5] arylcarboxylic acid derivatives,[6] or arylsul-
fonyl chlorides.[7] These aryl sources are generally believed
to undergo oxidative addition to palladium(0) to generate
arylsulfonyl hydrazides could undergo an oxidative Mizoro-
ki–Heck-type reaction in the presence of molecular oxygen
to give structurally diverse polysubstituted alkenes in a
highly regio- and stereoselective manner. Although arylsul-
fonyl hydrazides are readily accessible and are widely used
in chemical synthesis,[15] they have been demonstrated for
the first time by our study to be capable of undergoing a de-
À
sulfitative carbon carbon bond-forming reaction.
Initially, treatment of p-toluenesulfonyl hydrazide (1a,
1.2 equiv) with styrene (2a) and 10 mol% of PdACTHNUGTRENUNG(OAc)2 in
nitromethane under air at 708C led to the formation of
alkene 3a in 53% yield and with exclusive E selectivity
(Table 1, entry 1). Control experiments indicated that the
oxidant was essential for the desired reaction, and a slightly
better yield (55%) was obtained from the reaction with mo-
lecular oxygen under normal pressure (Table 1, entries 2 and
3). A range of solvents were examined, and the use of a 1:1
mixture of DMSO/MeNO2 dramatically enhanced the yield
up to 89% (Table 1, entry 12). Reducing the catalyst loading
significantly decreased the yield (Table 1, entry 13), and re-
placing PdACTHNUGRTENUNG(OAc)2 with a few other palladium catalysts led
to much lower yields or even no desired product at all
(Table 1, entries 14-16).
The substrate scope was found to be very general for the
oxidative Mizoroki–Heck-type reaction under the optimized
reaction conditions. In the presence of 10 mol% of Pd-
À
arylpalladium(II) species that will form carbon carbon
bonds with alkenes.[2]
Alternatively, the arylpalladium(II) species needed in the
Mizoroki–Heck reaction can be generated under oxidative
conditions from palladium(II) and aryl sources such as aro-
matics,[8] arylcarboxylic acids,[9] arylboronic acids or esters,[10]
arylphosphonic acids,[11] arylsulfinic acids (or sodium
salts),[12] and arylhydrazines.[13] These oxidative Mizoroki–
Heck-type reactions significantly expand the scope for ste-
reoselective alkene synthesis, but each has its own limita-
tions. To further address scope, selectivity, and productivity
issues, it constitutes a powerful strategy to explore new aryl
sources that are readily accessible and have decent reactivity
under mild conditions. In the course of developing new
methods for alkene synthesis,[14] we unexpectedly found that
AHCTUNGRTEGNUN(N OAc)2 and molecular oxygen under normal pressure, a
range of arylsulfonyl hydrazides smoothly underwent the ox-
idative Mizoroki–Heck-type reaction with monosubstituted
alkene 2a to give the corresponding 1,2-disubstituted al-
kenes in good to excellent yields and with excellent regiose-
lectivity and E selectivity (Table 2, entries 1–15).[16] It is
noteworthy that either an electron-withdrawing or an elec-
tron-donating group was introduced into the alkene product
by employing an arylsulfonyl hydrazide bearing such a
group on the aromatic ring. In addition, a gram-scale synthe-
sis of alkene 3a was successfully performed under the same
reaction conditions (1.29 g, 83% yield, >99:1 E/Z). The re-
action was successfully extended to a variety of monosubsti-
tuted alkenes such as arylethenes, N-protected allylamines,
allylsulfones, homoallyl alcohols, homoallyl esters, acrylic
acid, acrylates, and acrylamides (Table 2, entries 16–27). As
demonstrated by the results summarized in Table 2, this re-
action well tolerated a wide variety of functional groups
such as alkoxy, halo, alcohol, carboxylic acid, ester, amide,
sulfonamide, and sulfone.
[a] F.-L. Yang, X.-T. Ma, Prof. Dr. S.-K. Tian
Joint Laboratory of Green Synthetic Chemistry
Department of Chemistry
University of Science and Technology of China
Hefei, Anhui 230026 (P. R. China)
Fax : (+86)0551-3601592
[b] Prof. Dr. S.-K. Tian
Key Laboratory of Synthetic Chemistry of Natural Substances
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
354 Fenglin Road
Shanghai 200032 (P. R. China)
Supporting information for this article is available on the WWW
1582
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 1582 – 1585