DOI: 10.1002/chem.201405172
Communication
&
Organic Chemistry |Hot Paper|
Using N-Tosylhydrazone as a Double Nucleophile in the
Palladium-Catalyzed Cross-Coupling Reaction to Synthesize Allylic
Sulfones
Ping-Xin Zhou,[a] Yu-Ying Ye,[a] Lian-Biao Zhao,[b] Jian-Ye Hou,[c] Xing Kang,[a] Dao-
Qian Chen,[a] Qian Tang,[a] Jie-Yu Zhang,[a] Qi-Xing Huang,[a] Lan Zheng,[a] Jun-Wei Ma,[a]
Peng-Fei Xu,*[a] and Yong-Min Liang*[a]
um-catalyzed stabilized diazo compound insertion reaction
was reported by Van Vranken and co-workers in 2001.[5,6] Diazo
Abstract: Without extra addition of sulfinate salt, allylic
sulfones were synthesized by palladium-catalyzed cross-
compounds without an electron-withdrawing group on the
diazo carbon, such as diazoalkanes and aryldiazomethanes, are
coupling of aryl iodide with N-tosylhydrazone. In this
generally highly reactive and difficult to handle. To expand the
transformation, not only the diazo compound but also the
scope of this type of reaction and the practical utility of this
sulfinate salt, which were both generated in situ from
protocol, Barluenga and co-workers reported the first example
base-mediated decomposition of the N-tosylhydrazone,
of using N-tosylhydrazones as precursors of unstabilized diazo
was used as nucleophilic partner.
substrates in the palladium-catalyzed cross-coupling reaction
in 2007.[7] Since then, a series of palladium-catalyzed insertions
of N-tosylhydrazones were developed.[8] For example, Wang
The allylic sulfone skeleton has been found in numerous of
compounds exhibiting important biological activities, such as
treatment of Alzheimer’s disease, cancer, antibacterial agents,
and herbicides etc.[1] Moreover, because of the activation of a-
sulfonyl carbanions, allylic sulfones are used as efficient tools
for carbon–carbon bond-forming reactions (Ramberg–Bꢀcklund
reaction, Julia olefinations etc.).[2] Much attention has been
paid to prepare allylic sulfones. The oxidation of sulfides to the
corresponding sulfones is the most favored method. However,
this method often needs to employ high oxidant loading to
control the synthesis of sulfoxides and sulfones.[3] Allylic substi-
tution reaction with sulfinate salts is also a general approach.
But these transformations have their own drawbacks, such as
expensive catalysts, high catalyst loading, and excess addi-
tive.[4] In light of those limitations, a new, efficient, environ-
mental, and atom economic way to synthesize allylic sulfones
is highly desirable.
and co-workers demonstrated that under oxidative conditions,
N- tosylhydrazones could also undergo cross-coupling with ter-
minal alkynes.[9] They also reported a three-component cou-
pling of aryl halides, N-tosylhydrazones, and terminal alkynes
for the synthesis of propargylarenes.[10] The palladium-cata-
lyzed carbenylative amination with N-tosylhydrazones was
shown by Van Vranken.[11] Jiang described a Pd-catalyzed inter-
molecular cross-coupling reaction of terminal alkenes and N-
tosylhydrazones.[12] In 2014, we reported the example of utility
N-tosylhydrazones as a coupling partner in the Catellani–Laut-
ens reaction.[13] For all of those reactions, decomposition of the
tosylhydrazone generated the sulfinate salt. As we all know,
sulfinate salt is also a good nucleophilic coupling partner in
the palladium-catalyzed reaction.[14] However, using diazo com-
pound and sulfinate salt, which are generated in situ from N-
tosylhydrazone, both as nucleophilic coupling partners in one
reaction has not been reported in the literature to date. From
an environmental and atom economic view and for our inter-
est in this field,[13,15] here we report a new palladium-catalyzed
N-tosylhydrazones insertion reaction, in which not only diazo
compounds (generated in situ from N-tosylhydrazone) but also
the byproduct sulfinate salt (generated in situ from N-tosylhy-
drazone) is used as a nucleophilic coupling partner.
Recently, diazo compounds have been considered as a new
type of nucleophilic coupling partner in the palladium-cata-
lyzed cross-coupling reaction. The initial work of the palladi-
[a] P.-X. Zhou, Dr. Y.-Y. Ye, X. Kang, D.-Q. Chen, Q. Tang, J.-Y. Zhang,
Q.-X. Huang, L. Zheng, J.-W. Ma, Prof. P.-F. Xu, Prof. Y.-M. Liang
State Key Laboratory of Applied Organic Chemistry
Lanzhou University, Lanzhou 730000 (P.R. China)
Fax: (+86)931-8912582
To demonstrate the feasibility of this hypothesis, we began
our investigation by employing iodobenzene 1a and a,b-unsa-
turated N-tosylhydrazones 2a as the substrate. At the outset
of this investigation, the reaction was catalyzed by
[Pd2(dba)3]·CHCl3 (2.5 mol%)/PPh3 (15 mol%) (dba=dibenzyli-
deneacetone) in the presence of Cs2CO3 and BnNEt3Cl in tolu-
ene at 508C for 10 h (Table 1, entry 1). However, only a small
amount of product 3a was detected. Different mono- and bi-
dentate phosphine ligands were envisioned and it was found
that the yield was not improved (entries 2–6). Further inspec-
[b] Dr. L.-B. Zhao
College of Chemical Engineering
Northwest University for Nationalities, Lanzhou (P.R. China)
[c] Dr. J.-Y. Hou
Xinyang College of Agriculture and Forestry, Xinyang (P.R. China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201405172.
Chem. Eur. J. 2014, 20, 1 – 5
1
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
Zhou, Ping-Xin
