Cross-coupling of N-allylic sulfonimides with organozinc reagents at room temperature

Article abstract of DOI:10.1002/ejoc.201200594

An efficient cross-coupling reaction of N-allylic sulfonimides with organozinc reagents has been developed. In the presence of 1 mol-% of Pd ₂(dba)₃, a range of N-allylic sulfonimides smoothly couple with various organozinc reagents at room temperature to give the corresponding (E)-alkene products in moderate to excellent yields and with good to exclusive α-selectivity. It is noteworthy that allyl ether, benzyl ether, and ester are tolerated under the reaction conditions. A range of N-allylic sulfonimides smoothly couple with various organozinc reagents in the presence of 1 mol-% of Pd₂(dba)₃ at room temperature to give the corresponding (E)-alkene products in moderate to excellent yields and with good to exclusive α-selectivity.

Full text of DOI:10.1002/ejoc.201200594

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SHORT COMMUNICATION
DOI: 10.1002/ejoc.201200594
Cross-Coupling of N-Allylic Sulfonimides with Organozinc Reagents at Room
Temperature
Xiang-Ling Tang,[a] Zhao Wu,[a] Man-Bo Li,[a] Yonghong Gu,*[a] and Shi-Kai Tian*[a,b]
Keywords: Sulfur / Alkenes / Cross-coupling / Zinc / Palladium
An efficient cross-coupling reaction of N-allylic sulfonimides
with organozinc reagents has been developed. In the pres-
ence of 1 mol-% of Pd2(dba)3, a range of N-allylic sulfon-
imides smoothly couple with various organozinc reagents at
room temperature to give the corresponding (E)-alkene prod-
ucts in moderate to excellent yields and with good to exclus-
ive α-selectivity. It is noteworthy that allyl ether, benzyl ether,
and ester are tolerated under the reaction conditions.
activate allylic electrophiles through the generation of π-
allylpalladium intermediates[7] and that they mediate a
number of reactions with organozinc reagents,[8] we exam-
ined a few palladium sources (1–2 mol-%), most of which
were effective in promoting the desired sp3 C–N bond cleav-
age and minimizing the N–S bond cleavage (Table 1, En-
tries 2–7). Pd2(dba)3 was identified as the palladium source
of choice, the use of which led to the formation of the de-
sired product, alkene 4a, in 92% yield (Table 1, Entry 2). A
few nickel and copper sources were also examined, but they
failed to promote the model reaction (Table 1, Entries 8–
10). Replacing the N-p-toluenesulfonyl group in substrate
1a with a methanesulfonyl group led to a lower yield (87%;
Table 1, Entry 11).
Introduction
Whereas primary allylic amines are widely employed as
nitrogen nucleophiles in chemical synthesis, they rarely
serve as useful carbon electrophiles due to the extremely
poor leaving ability of their amino groups.[1] Previous stud-
ies show that the introduction of electron-withdrawing
groups to the allylic amine nitrogen atoms can significantly
activate sp3 C–N bonds and consequently enhance the leav-
ing ability of amino groups.[2] Particularly, doubly sulfonyl-
activated allylic amines, N-allylic sulfonimides, can serve as
unique carbon electrophiles under basic conditions to cou-
ple with carbon nucleophiles such as malonates,[3] organo-
cuprates,[4] and Grignard reagents.[5,6] In the course of ex-
panding the scope of carbon nucleophiles, we found that
organozinc reagents could couple with N-allylic sulfon-
imides at room temperature through selective cleavage of the
sp3 C–N bonds rather than the N–S bonds. This study sig-
nificantly extends the applications of primary allylic amine
derivatives as allylic electrophiles in chemical synthesis.
Table 1. Optimization of the reaction conditions.[a]
Results and Discussion
The model reaction of N-allylic sulfonimide 1a with
PhZnCl (2a) was found to be very sluggish in dry tetra-
hydrofuran at room temperature (Table 1, Entry 1). Recog-
nizing that palladium catalysts are frequently employed to
[a] Joint Laboratory of Green Synthetic Chemistry, Department
of Chemistry, University of Science and Technology of China,
Hefei,
Anhui 230026, China
Fax: +86-0551-3601592
E-mail: ygu01@ustc.edu.cn
tiansk@ustc.edu.cn
[a] Reaction conditions: sulfonimide 1a or 1ab (0.50 mmol), or-
ganozinc reagent 2a (0.60 mmol), catalyst (1–2 mol-%), tetra-
hydrofuran (2.5 mL), 25 °C, 0.5 h. [b] Isolated yield. Ts = p-tolu-
enesulfonyl, Ms = methanesulfonyl, dba = dibenzylideneacetone,
dppf = 1,1Ј-bis(diphenylphosphanyl)ferrocene, Tf = trifluoro-
methanesulfonyl.
[b] Key Laboratory of Synthetic Chemistry of Natural Substances,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences,
Shanghai 200032, China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200594.
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X.-L. Tang, Z. Wu, M.-B. Li, Y. Gu, S.-K. Tian
SHORT COMMUNICATION
Table 2. Cross-coupling of N-allylic sulfonimides with organozinc reagents.[a]
[a] Reaction conditions: sulfonimide 1 (0.50 mmol), organozinc reagent 2 (0.60 mmol), Pd2(dba)3 (1 mol-%), tetrahydrofuran (2.5 mL),
1
25 °C. [b] Determined by H NMR spectroscopy. [c] Isolated yield.
In the presence of 1 mol-% of Pd2(dba)3, a range of N- ganozinc reagent 2 followed by reductive elimination to give
allylic sulfonimides smoothly coupled with various or- alkene 4, which regenerates the palladium(0) catalyst. The
ganozinc reagents at room temperature to give the corre- generation of π-allylpalladium complex 6 as an intermedi-
sponding alkene products in moderate to excellent yields ate during the reaction accounts for the stereoconvergence
(Table 2). While the alkene geometry was retained in the and the formation of alkene 5 as a minor product in some
reaction with (E)-N-allylic sulfonimides, it was mostly in- cases (Table 2, Entries 6–8 and 11).
verted in the reaction with (Z)-N-allylic sulfonimides
(Table 2, Entry 11). The stereoconvergence could be attrib-
utable to the generation of a π-allylpalladium intermediate
from the palladium catalyst and the N-allylic sulfonimide
(vide infra),[7] and the reaction preferred to give (E)-alkenes
under thermodynamic conditions. When the R1 group in
the sulfonimide was an aryl or a heteroaryl group, the reac-
tion proceeded with exclusive α-selectivity probably due to
the maintenance of a maximum degree of conjugation and
the minimization of steric hindrance. In contrast, inferior
α-selectivity was achieved in some cases wherein the R1
group was an alkyl group (Table 2, Entries 6–8 and 11). It
is noteworthy that allyl ether, benzyl ether, and ester were
tolerated under our reaction conditions (Table 2, Entries 7,
11, and 19). In addition, bulky organozinc reagents proved
to be suitable carbon nucleophiles to couple with N-allylic
sulfonimides (Table 2, Entries 10, 14, and 15).
Scheme 1. Proposed reaction pathway.
Conclusions
On the basis of our results and the general mechanism
In conclusion, we have developed, for the first time, an
of palladium catalysis,[7,8] we propose the reaction pathway efficient cross-coupling reaction of N-allylic sulfonimides
depicted in Scheme 1 for the cross-coupling of N-allylic with organozinc reagents. In the presence of 1 mol-% of
sulfonimides with organozinc reagents. The allylic C–N Pd2(dba)3, a range of N-allylic sulfonimides smoothly cou-
bond of N-allylic sulfonamide 1 is cleaved through oxidative ple with various organozinc reagents at room temperature
addition by the palladium(0) catalyst to give π-allylpalla- to give the corresponding (E)-alkene products in moderate
dium complex 6, which undergoes transmetalation with or- to excellent yields and with good to exclusive α-selectivity.
2
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Cross-Coupling of N-Allylic Sulfonimides with Organozinc Reagents
It is noteworthy that allyl ether, benzyl ether, and ester are
tolerated under the reaction conditions.
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[2] a) H. J. Lee, M. R. Seong, J. N. Kim, Tetrahedron Lett. 1998,
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2011, 47, 8343–8345; f) Z.-Y. Jiang, C.-H. Zhang, F.-L. Gu,
K.-F. Yang, G.-Q. Lai, L.-W. Xu, C.-G. Xia, Synlett 2010,
1251–1254.
Experimental Section
General Procedure for the Cross-Coupling of N-Allylic Sulfonimides
with Organozinc Reagents: A Schlenk tube was charged with sulf-
onimide 1 (0.50 mmol), tetrahydrofuran (0.50 mL), and Pd2(dba)3
(4.6 mg, 0.005 mmol, 1 mol-%). To the stirred mixture was added
a solution of organozinc reagent 2 (0.30 m in THF, 2.0 mL,
0.60 mmol) by syringe. The reaction mixture was stirred under an
atmosphere of nitrogen at room temperature until no further trans-
formation was observed by TLC analysis. HCl (1.0 m, 5.0 mL) was
added, and the mixture was extracted with ethyl acetate (2ϫ
20 mL). The combined organic extracts were dried with anhydrous
magnesium sulfate and concentrated. The residue was purified by
preparative TLC, developing with petroleum ether, to afford com-
pounds 4 and 5 (if any).
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[5] M.-B. Li, X.-L. Tang, S.-K. Tian, Adv. Synth. Catal. 2011, 353,
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[6] For examples with nitrogen and oxygen nucleophiles, see: a)
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Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data, and copies of
1
the H NMR and 13C NMR spectra for the products.
Acknowledgments
We are grateful for financial support from the National Natural
Science Foundation of China (21172206, 21072180, 20972147,
J1030412), the National Basic Research Program of China (973
Program 2010CB833300), and the Program for Changjiang Schol-
ars and Innovative Research Team in University (IRT1189).
Received: May 7, 2012
Published Online: ᭿
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X.-L. Tang, Z. Wu, M.-B. Li, Y. Gu, S.-K. Tian
SHORT COMMUNICATION
Cross-Coupling
X.-L. Tang, Z. Wu, M.-B. Li, Y. Gu,*
S.-K. Tian* ....................................... 1–4
Cross-Coupling of N-Allylic Sulfonimides
with Organozinc Reagents at Room Tem-
perature
A range of N-allylic sulfonimides smoothly
couple with various organozinc reagents in
the presence of 1 mol-% of Pd2(dba)3 at
room temperature to give the correspond-
ing (E)-alkene products in moderate to ex-
cellent yields and with good to exclusive α-
selectivity.
Keywords: Sulfur / Alkenes / Cross-cou-
pling / Zinc / Palladium
4
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Eur. J. Org. Chem. 0000, 0–0