COMMUNICATION
“This is the peer reviewed version of the following article: Chem. Eur. J. 2018, 24, 19156-19161, which has been published in final
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COMMUNICATION
Diversity-Orientated

Stereoselective

Synthesis

through

Pd-

Catalyzed Switchable Decarboxylative C‒N/C‒S Bond Formation
in Allylic Surrogates
Lei Deng,[a,b,c] Arjan W. Kleij*[e,f] and Weibo Yang*[a,b,d]
Abstract: Switchable catalytic transformation of reactants can be a
powerful approach towards diversity-orientated synthesis from easily
available molecular synthons. Herein, an endogenous ligandcontrolled, Pd-catalyzed allylic substitution allowing for either
selective C‒N or C‒S bond formation using vinylethylene carbonates
and N-sulfonylhydrazones as coupling partners has been developed.
This versatile methodology provides a facile, diversicating route for
the highly chemo- and stereoselective synthesis of functional allylic
sulfones or sulfonohydrazides. The newly developed protocol
features wide substrate scope (nearly 80 examples), broad functional
group tolerance and potential for the late-stage functionalization of
bioactive compounds. The isolation and crystallographic analysis of a
catalytically competent -allyl Pd complex suggests that the pathway
leading to the allylic products proceeds through a different manifold
as previously proposed for the functionalization of VECs with
nucleophiles.

Diversity-oriented synthesis aims to generate diverse
structural motifs with a broad range of biological activities in a
concise and efficient manner, and has thus received much
attention in synthetic organic and medicinal communities. [1]
Undoubtedly, controllable and switchable strategies have
emerged as a powerful tool to significantly increase the diversity
and complexity of molecular architectures using reactants with
tunable reactivity.[2] Vinylethylene carbonates (VECs)[3] have
become popular substrates in transition metal catalyzed
transformations including allylic substitution reactions.[4] For
example, highly regio-, stereo and enantioselective Pd-catalyzed
allylic substitutions of VECs with water,[3o] amines[3p,3r] or thiols[3q]
to deliver valuable building synthetic blocks have been reported.
In addition, Zhang et al. disclosed an elegant approach for the Pdcatalyzed asymmetric allylic substitution of VECs with water or
alcohols towards the formation of branched allylic ethers and
alcohols featuring chiral tertiary carbon centers.[3m]
Notably, all these reported protocols exclusively employ the
use of single nucleophiles in allylic substitution reactions of which

[a]
[b]
[c]
[d]
[e]

[f]

Chinese Academy of Sciences, Key Laboratory of Receptor
Research, Shanghai Institute of Materia Medica, Shanghai, China;
University of Chinese Academy of Sciences, Beijing, China. E-mail:
yweibo@simm.ac.cn
Nano Science and Technology Institute, University of Science and
Technology of China, Suzhou, Jiangsu 215123, China
University of Science and Technology Liaoning, Anshan 114051, P.
R. China.
Institute of Chemical Research of Catalonia (ICIQ), Av. Països
Catalans 16, 43007 – Tarragona (Spain)
E-mail: akleij@iciq.es
Catalan Institution of Research and Advanced Studies (ICREA), Pg.
Lluis Companys 23, 08010 – Barcelona (Spain)
Supporting information for this article is given via a link at the end of
the document.

the regio- and stereo-bias is ligand-controlled (Scheme 1a). To
the best of our knowledge, the chemo-switchable and
stereoselective Pd-catalyzed allylic substitution of VECs in the
presence of substrates incorporating different pro-nucleophilic
sites remains elusive to date despite its potential to provide
through a single process a much higher degree of molecular
diversity (Scheme 1b).

Scheme 1. (a) Reported Pd-catalyzed allylic substitution reactions using VECs,
(b) new conceptual diversity orientated approach, and (c) reaction design
applied in this work.

In order to address this challenge (Scheme 2b), we
envisioned the use of well-known and robust Nsulfonylhydrazones as coupling partners.[5] From this versatile
coupling partner three distinct intermediates can be generated
including ambiphilic metal carbenes, sulfur nucleophiles as well
as nucleophilic nitrogen species in the presence of suitable metals
under basic conditions. Whereas the ambiphilic metal carbene
intermediates have been widely utilized in transition metal
catalyzed C‒C bond formation,[5b] the use of the S- and Nnucleophilic species in synthetic chemistry is still in its infancy.
Therefore, the exploration of such unmapped chemical space can
create new opportunities for diversity-orientated synthesis. Based
on the previous successful accomplishments with Ntosylhydrazones[5b,6] and VECs[3i, 3l, 3o-r] in preparative chemistry,
we hypothesized that activated N-sulfonylhydrazones could trap
the allyl-Pd intermediate after decarboxylation of the VEC. By
carefully manipulating the reaction conditions and ligands, either
S-based or N-based nucleophiles may be generated in situ

COMMUNICATION
thereby creating a useful diversicating approach from a single set
of substrates (Scheme 1c). Herein, we report the first example of
a conceptually divergent, Pd-catalyzed stereoselective allylic
substitution of VECs. This chemo-switchable C‒N and C‒S bond
formation is scrutinized by the presence of simple endogenous
ligands. Moreover, this protocol allows for easy access to
multifunctional allylic scaffolds of importance in organic
synthesis[7] and being frequently encountered in many bioactive
natural products.[8]
Table 1. Optimization of the reaction conditions towards selective formation
of allylic sulfone 3aa or allylic hydrazone 4aa.[a]

Entry

Catalyst

Base (equiv)

Solv.

3aa[b]

4aa[b]

1

Pd2(dba)3

K2CO3 (2.4)

Diox

47% (87:13)

19%

2

Pd2(dba)3

K2CO3 (2.4)

DMF

46% (80:20)

‒

3

Pd2(dba)3

K2CO3 (2.4)

MeCN

68% (93:7)

17%

4

Pd2(dba)3

Na2CO3 (2.4)

MeCN

trace

trace

5

Pd2(dba)3

Et3N (2.4)

MeCN

trace

trace

6

Pd2(dba)3

Cs2CO3 (2.4)

MeCN

39% (82:18)

‒

7

Pd2(dba)3

CsF (2.4)

MeCN

64% (93:7)

16%

8

Pd2(dba)3

K2CO3 (2.0)

MeCN

68% (94:6)

17%

9

Pd2(dba)3

K2CO3 (1.0)

MeCN

69% (94:6)

8%

10

Pd2(dba)3

K2CO3 (0.8)

MeCN

71% (94:6)

6%

11

Pd2(dba)3

K2CO3 (2.4)

MeCN

61% (92:8)

14%

12

Pd(OAc)2

K2CO3 (2.4)

MeCN

56% 89:11)

8%

13

PdCl2

K2CO3 (2.4)

MeCN

60% (92:8)

21%

14

Pd(PPh3)4

K2CO3 (2.4)

MeCN

‒

chemoselectivity was noted (Table 1, entry 3; 3aa:4aa = 4:1, for
3aa, Z/E = 93:7). These combined results highlight the challenge
of simultaneous achieving high chemo- and stereoselectivity, and
encouraged us to investigate the influence of different bases. The
use of both Na2CO3 and Et3N was unproductive (entries 4 and 5),
and the presence of either Cs2CO3 or CsF did not further improve
the results (entries 6 and 7). Gratifyingly, decreasing the amount
of K2CO3 (cf., entries 8-10) to 0.8 equiv provided optimal chemoand stereoselectivity towards 3aa (entry 10; yield 71%, Z/E =
94:6). Variation of the Pd precursor was also examined (entries
11-14), and when a mixture of 1a and 2a was treated with
Pd(PPh3)4 and K2CO3 in CH3CN (entry 14), exclusively C‒N bond
formation could be achieved giving allylic hydrazone 4aa in 94%
yield and in excellent stereoselectivity (Z/E >99:1). This complete
switch in chemoselectivity may be attributed to stronger 
interactions between the PPh3 ligand and nucleophilic
intermediate obtained from 2a, and notably no exogenous ligand
was required to induce this switch in chemoselectivity.

94%[c]

[a] Reaction conditions: 1a (0.05 mmol), 2a (0.1 mmol), [Pd] (5 mol %) in solvent
(0.5 mL) at 80 ºC for 2 h; Diox stands for 1,4-dioxane, note that Pd2(dba)3 here
reflects the use of the CHCl3 solvate. [b] The yield of (Z)-3aa and (Z)-4aa was
determined by the 1H NMR using CH2Br2 as an internal standard; the Z/E ratios
were determined from the crude product by 1H NMR and values are reported in
brackets. [c] The Z/E ratio of the product was >99:1.

Inspired by the challenge presented in Scheme 1b, we set out
to examine the feasibility of this conceptual approach using the
model VEC substrate 1a and N-tosylhydrazone 2a. To our delight,
an initial trial (Table 1, entry 1) revealed that a catalytic system
comprising Pd2(dba)3·CHCl3 and K2CO3 gave rise to both C‒S
and C‒N bond formation products albeit with unsatisfactory
chemo- and stereoselectivity. The (Z)-configuration of 3aa and
4aa were confirmed by NOE analysis. When DMF was utilized as
solvent under similar conditions, only 3aa was produced in
excellent chemoselectivity but with moderate stereocontrol (entry
2; 46% yield, Z/E = 80:20). Further solvent screening indicated
that the overall conversion and stereoselectivity of 3aa could be
significantly enhanced in CH3CN though some erosion of the

Scheme 2. The scope of allylic sulfones 3 derived from various VECs and Nsulfonylhydrazones using the reaction conditions of Table 1, entry 10. Reported
yields are of the isolated product.

With the optimized conditions in hand, first the scope of the
Pd-catalyzed allylic sulfone formation was explored varying both
the VEC and N-sulfonylhydrazone substrate (Scheme 2).[9] A
series of para-, meta- and ortho-monosubstituted aryl groups in
the substituted VECs with either electron-donating or electronwithdrawing character are well-tolerated by the developed
protocol to afford 3ba‒3ka in moderate to good yields with
excellent chemo- (typically >90%) and stereoselectivity (for 3ba
X-ray analysis confirmed the major isomer, see also the
Supporting Information, SI).[10] Particularly, substrates bearing
chloro or bromo functional groups were also amenable to the
standard conditions (3ga and 3la), thus offering potential for

COMMUNICATION
further functionalization. The catalytic system also showed
compatibility with sulfur-containing VECs allowing to isolate 3ma
in high yield without any sign of catalyst deactivation. The R1
group of the VEC could be extended to aliphatic substituents such
as methyl (3na), cyclohexyl (3oa) and tetrahydropyranyl (3pa)
and all provided reasonable yields under high stereoinduction.
Cycloalkyl groups with fused aromatic rings (3qa and 3ra) could
also be introduced in the allylic sulfone product while maintaining
high chemo- and stereoselectivity.

The scope of the Pd-catalyzed formation of allylic
sulfonohydrazides was also evaluated (Scheme 3). The substrate
scope of these reactions also proved extensive, and in the
majority of the cases excellent chemo- and stereoselectivity was
observed regardless the electronic and steric properties of the
substrates. Aryl groups in the VECs with different types of
substitution (ortho, meta or para) were endorsed by the catalytic
procedure (cf., compounds 4ba4la), while the presence of
various heterocyclic, vinyl and alkyl groups also allowed to deliver
allylic sulfonohydrazides 4ma4ra in good yield and under high
stereo-control except for 4ta (Z/E = 74:26).
The generality of this CN bond formation protocol could be
further illustrated by successful synthesis of various allylic
sulfonohydrazides (cf., products 4ab4at) that comprise a variety
of heterocyclic groups such as naphthyl, pyridyl, (substituted)
thiophenelyl, furyl, morpholinyl and piperidinyl, and substituted
aromatics with potentially useful nitro (4af) and halide
substituents (4ae, 4ah and 4ak). In all aforementioned examples,
formation of the targeted products was observed with good yields
(typically >70%) with excellent Z/E ratios of up >99:1.

Scheme 3. The scope of allylic sulfonohydrazides 4 derived from various VECs
and N-sulfonylhydrazones using the reaction conditions of Table 1, entry 14.
Reported yields are of the isolated product.

Subsequently, a series of substituted N-tosylhydrazone
substrates was tested (Scheme 2, lower part; compounds 3ab‒
3am) and those having aryl groups with electron-donating
substituents favored higher yields than those with electronwithdrawing groups. Apart from simple aromatic rings, also
naphthyl (3aj), cyclopropyl (3al) and 3-pyridyl (3am) could be
introduced in the allylic sulfone product being relevant to targetoriented synthesis. For the latter derivative, a lower
chemoselectivity was observed, though excellent stereoselectivity
could be achieved.

Scheme 4. Late-stage functionalization of biologically important scaffolds with
allylic sulfone or sulfonohydrazide groups. Reported yields are of the isolated
product.

COMMUNICATION
Fragment-based drug design has emerged as a crucial
strategy to accelerate lead compound identification,[11] and this
encouraged us to use our develop protocol for late-stage
functionalization of important drug scaffolds (Scheme 4; see also
the SI for further details). We first prepared Erlotinib (used in lung
cancer treatment)[12] and Pregnenolone (neuroprotecting
agent)[13] analogues by incorporating VEC fragments. The latestage functionalization of these two biologically relevant scaffolds
was successfully accomplished (compounds 3ua, 4ua, 3va and
4va) and allowed the introduction of functionalized allylic sulfone
and
sulfonohydrazide
groups.
Alternatively,
Erlotinib,
Pregnenolone, Fenofibrate,[14] and Testosterone[15] could be
easily substituted with N-tosylhydrazones which after treatment
with VEC 1a under the optimal conditions (Table 1, entry 14) gave
smooth access to the products 4ay, 4az, 5aa, and 5ab in high
yields and with excellent stereocontrol.

isolated in 83% yield. When the same substrates were treated in
the presence of a catalytic amount of PPh3, the chemoselectivity
was completely reversed towards the formation of the allylic
sulfonohydrazide 4aa (90% yield). Both yields obtained for 3aa
and 4aa in the presence of 9 were improved compared to those
experiments relying on in situ preparation of the active catalyst,
and indeed suggest that a Pd(allyl) intermediate similar to 9 may
be a catalytic intermediate with the presence of the phosphine
ligand exerting a crucial role in the switching of the chemoselectivity.[17]

N
Pd

O
Cl
O

Scheme 5. Gram-scale reaction of 3aa and further transformations furnishing
6a8a. All reported yields are from the isolated product. See for details the SI.

We further evaluated the robustness and practicality of allylic
sulfone formation reactions (Scheme 5) using 3aa as a
representative case, which could be easily prepared on gram
scale. The alcohol fragment in 3aa could be conveniently oxidized
to an aldehyde through a Dess-Martin oxidation, whereas the
double bond in 3aa could be reduced using a Pd/C catalyst under
H2 to give product 7a in 87% yield. Treatment of 3aa under
standard Mitsunobu reaction conditions afforded 8a, whereas the
allylic sulfone could also be a viable starting point for the formation
of 1,3-oxazolidines based on [3+2] cycloaddition reaction recently
reported by Terada and coworkers.[16]
Several experiments were conducted to gain insight into the
mechanism of this Pd-catalyzed switchable allylic CN/CS bond
formation process (Scheme 6, top). Treatment of a stoichiometric
combination of [Pd2(dba)3]·CHCl3 and VEC 1a in CH3CN while
adding 2-acetylpyridine resulted in decarboxylation and afforded
unexpectedly the -allyl Pd complex 9 in 45% isolated yield.
Complex 9 was fully characterized by 1H and 13C NMR, and X-ray
crystallography.[10] The structure of 9 reveals that the Pd center is
3-ligated by the allyl fragment and the hydromethyl group is
orientated syn to the metal center. Such a -allyl Pd complex is
rather distinct from the DFT-computed six-membered
palladacycle recently determined in the functionalization of VECs
with various nucleophiles.[3f,i,q,v] To examine whether this Pdcomplex 9 is catalytically competent, it was subjected to the
optimized conditions reported in Table 1. First, 9 was combined
with substrates 1a and 2a, and allylic sulfone 3aa could be

Scheme 6. Mechanistic control experiments (top) and proposed manifolds for
the formation of the allylic sulfones and sulfonohydrazides (bottom).

On the basis of these mechanistic control reactions and
previous reports, we propose that the synthesis of the allylic
products starts off with the decarboxylative oxidative addition of
the VEC (here 1a used as a representative case) to the Pd(0)
precursor generating a -allyl palladium intermediate similar to 9.
From here the reaction proceeds via nucleophilic attack onto this
Pd(allyl) intermediate involving either CS or CN bond formation
providing selectively the allylic sulfone (via Nu2) or
sulfonohydrazide (via Nu1) and regenerating the requisite Pd(0)
catalyst for subsequent turnover. The type of nucleophile that is
generated in situ can be regulated under basic conditions.

COMMUNICATION
In summary, we have developed the first example of a chemoswitchable allylic CN or CS bond formation reaction through an
endogenous ligand-controlled, Pd-catalyzed conversion of
versatile vinylethylene carbonate and N-sulfonylhydrazone
substrates. This developed protocol exhibits broad substrate
scope and excellent functional group tolerance important for
diversity-orientated synthesis and drug discovery. The catalytic
methodology can also be applied to late-stage functionalization of
bioactive scaffolds by introduction of various allylic fragments.
Further
diversity-oriented
transition
metal
mediated
transformations are currently targeted to further expand this
conceptual approach.

[4]
[5]

Acknowledgements
[6]

We gratefully acknowledge 100 talent program of Chinese
Academy of Sciences, Chinese NSF (21702217), "1000-Youth
Talents Plan", Shanghai-Youth Talent, Shanghai-Technology
innovation Action Plan (18JC1415300), the CERCA
Program/Generalitat de Catalunya, ICREA, the Spanish MINECO
(CTQ2017-88920-P), and AGAUR (2017-SGR-232) for support of
this research.
Keywords: allylic substitution • decarboxylation • Nsulfonylhydrazones • Pd catalysis • vinylethylene carbonates
[1]

[2]
[3]

a) E. Lenci, A. Guarna, A. Trabocchi, Molecules 2014, 19, 16506-16528;
b) W. R. Galloway, A. Isidro-Llobet, D. R. Spring, Nat. Commun. 2010, 1,
80; c) S. L. Schreiber, Science 2000, 287, 1964-1969.
Y. C. Lee, K. Kumar, H. Waldmann, Angew. Chem. Int. Ed. 2018, 57,
5212-5226.
a) C. Yuan, Y. Wu, D. Wang, Z. Zhang, C. Wang, L. Zhou, C. Zhang, B.
Song, H. Guo, Adv. Synth. Catal. 2018, 360, 652-658; b) L. C. Yang, Z.
Y. Tan, Z. Q. Rong, R. Liu, Y. N. Wang, Y. Zhao, Angew. Chem. Int. Ed.
2018, 57, 7860-7864; c) Y. N. Wang, L. C. Yang, Z. Q. Rong, T. L. Liu,
R. Liu, Y. Zhao, Angew. Chem. Int. Ed. 2018, 57, 1596-1600; d) S.
Singha, T. Patra, C. G. Daniliuc, F. Glorius, J. Am. Chem. Soc. 2018,
140, 3551-3554; e) I. Khan, C. Zhao, Y. J. Zhang, Chem. Commun. 2018,
54, 4708-4711; f) W. Guo, R. Kuniyil, J. E. Gomez, F. Maseras, A. W.
Kleij, J. Am. Chem. Soc. 2018, 140, 3981-3987; g) P. Das, S. Gondo, P.
Nagender, H. Uno, E. Tokunaga, N. Shibata, Chem. Sci. 2018, 9, 32763281; h) L. C. Yang, Z. Q. Rong, Y. N. Wang, Z. Y. Tan, M. Wang, Y.
Zhao, Angew. Chem. Int. Ed. 2017, 56, 2927-2931; i) J. Xie, W. Guo, A.
Cai, E. C. Escudero-Adan, A. W. Kleij, Org. Lett. 2017, 19, 6388-6391; j)
H. Wang, F. Pesciaioli, J. C. A. Oliveira, S. Warratz, L. Ackermann,
Angew. Chem. Int. Ed. 2017, 56, 15063-15067; k) Z. Q. Rong, L. C. Yang,
S. Liu, Z. Yu, Y. N. Wang, Z. Y. Tan, R. Z. Huang, Y. Lan, Y. Zhao, J.
Am. Chem. Soc. 2017, 139, 15304-15307; l) N. Miralles, J. E. Gomez, A.
W. Kleij, E. Fernandez, Org. Lett. 2017, 19, 6096-6099; m) A. Khan, S.
Khan, I. Khan, C. Zhao, Y. Mao, Y. Chen, Y. J. Zhang, J. Am. Chem. Soc.
2017, 139, 10733-10741; n) Y. Mao, X. Zhai, A. Khan, J. Cheng, X. Wu,
Y. J. Zhang, Tetrahedron Lett. 2016, 57, 3268-3271; o) W. Guo, L.
Martinez-Rodriguez, E. Martin, E. C. Escudero-Adan, A. W. Kleij, Angew.

[7]
[8]

[9]

[10]
[11]
[12]

[13]

[14]

[15]

[16]
[17]

Chem. Int. Ed. 2016, 55, 11037-11040; p) W. Guo, L. MartinezRodriguez, R. Kuniyil, E. Martin, E. C. Escudero-Adan, F. Maseras, A. W.
Kleij, J. Am. Chem. Soc. 2016, 138, 11970-11978; q) J. E. Gomez, W.
Guo, A. W. Kleij, Org. Lett. 2016, 18, 6042-6045; r) A. Cai, W. Guo, L.
Martinez-Rodriguez, A. W. Kleij, J. Am. Chem. Soc. 2016, 138, 1419414197; s) L. Yang, A. Khan, R. Zheng, L. Y. Jin, Y. J. Zhang, Org. Lett.
2015, 17, 6230-6233; t) A. Khan, J. Xing, J. Zhao, Y. Kan, W. Zhang, Y.
J. Zhang, Chem. Eur. J. 2015, 21, 120-124; u) A. Khan, R. Zheng, Y. Kan,
J. Ye, J. Xing, Y. J. Zhang, Angew. Chem. Int. Ed. 2014, 53, 6439-6442;
(v) A. Cristòfol, E. C. Escudero-Adán, A. W. Kleij, J. Org. Chem. 2018,
83, 9978-9990; For a recent review on the use of VECs: w) W. Guo, J.
E. Gomez, A. Cristofol, J. Xie, A. W. Kleij, Angew. Chem. Int. Ed. 2018,
57, 13735-13747
a) N. A. Butt, W. Zhang, Chem. Soc. Rev. 2015, 44, 7929-7967; b) B. M.
Trost, T. Zhang, J. D. Sieber, Chem. Sci. 2010, 1, 427-440.
a) Z. Shao, H. Zhang, Chem. Soc. Rev. 2012, 41, 560-572; b) Q. Xiao,
Y. Zhang, J. Wang, Acc. Chem. Res. 2013, 46, 236-247.
a) Y. Xia, J. Wang, Chem. Soc. Rev. 2017, 46, 2306-2362; b) Q. Sun, L.
Li, L. Liu, Q. Guan, Y. Yang, Z. Zha, Z. Wang, Org Lett. 2018, 20, 55925596; c) X. W. Feng, J. Wang, J. Zhang, J. Yang, N. Wang, X. Q. Yu,
Org Lett. 2010, 12, 4408-4411; d) S. Mao, Y. R. Gao, X. Q. Zhu, D. D.
Guo, Y. Q. Wang, Org Lett. 2015, 17, 1692-1695.
A. Lumbroso, M. L. Cooke, B. Breit, Angew. Chem. Int. Ed. 2013, 52,
1890-1932.
a) F. Reck, F. Zhou, M. Girardot, G. Kern, C. J. Eyermann, N. J. Hales,
R. R. Ramsay, M. B. Gravestock, J. Med. Chem. 2005, 48, 499-506; b)
B. Lim, E.-T. Oh, J. Im, K. S. Lee, H. Jung, M. Kim, D. Kim, J. T. Oh, S.H. Bae, W.-J. Chung, K.-H. Ahn, S. Koo, Eur. J. Org. Chem. 2017, 2017,
6390-6400.
For comparison, we also probed the reaction towards the formation of
product 3ad (yield: 62%, Z/E = 93:7; Scheme 2) using sodium ptolylsulfinate as a nucleophile. In the latter case, the yield for 3ad (74%)
was improved but at the expense of the stereoselectivity (Z/E = 86:14).
See Supporting Information for details, and CCDC-1869422 and
1869425.
A. Kumar, A. Voet, K. Y. J. Zhang, Curr. Med. Chem. 2012, 19, 51285147.
a) Y. Wang, G. Schmid-Bindert, C. Zhou, Ther. Adv. Med. Oncol. 2012,
4, 19-29; b) J. Tang, R. Salama, S. M. Gadgeel, F. H. Sarkar, A. Ahmad,
Front .Pharmacol. 2013, 4, 15.
a) S. Veiga, L. M. Garcia-Segura, I. Azcoitia, J. Neurobiol. 2003, 56, 398406; b) K. K. Borowicz, B. Piskorska, M. Banach, S. J. Czuczwar, Front.
Endocrinol. 2011, 2, 50.
a) K. K. Koh, S. H. Han, M. J. Quon, J. Yeal Ahn, E. K. Shin, Diabetes
Care 2005, 28, 1419-1424; b) A. Keech, R. J. Simes, P. Barter, J. Best,
R. Scott, M. R. Taskinen, P. Forder, A. Pillai, T. Davis, P. Glasziou, P.
Drury, Y. A. Kesaniemi, D. Sullivan, D. Hunt, P. Colman, M. d'Emden, M.
Whiting, C. Ehnholm, M. Laakso, Lancet 2005, 366, 1849-1861.
C. Wang, R. S. Swerdloff, A. Iranmanesh, A. Dobs, P. J. Snyder, G.
Cunningham, A. M. Matsumoto, T. Weber, N. Berman, J. Clin. Endocrinol.
Metab. 2000, 85, 2839-2853.
A. Kondoh, S. Akahira, M. Oishi, M. Terada, Angew. Chem. Int. Ed. 2018,
57, 6299-6303.
2-Acetylpyridine addition (5 mol%) during the catalytic reaction leads to
product 3aa (68%, Z/E = 91:9). The result is similar compared with the
optimized protocol provided in Table 1, entry 10 (yield of 3aa: 71%, Z/E
= 94:6). This may further indicate the existence of an allyl-Pd
intermediate as suggested in Scheme 6.

COMMUNICATION
Entry for the Table of Contents:

COMMUNICATION
Nucleophilic
Switch:
A
conceptually
attractive
and
switchable Pd-catalyzed allylic
substitution
of
vinylethylene
carbonates
with
sulfonylhydrazones has been developed
in the context of diversityorientated synthesis. The chemoswitchable CS and CN bond
formation reactions are highly
versatile, and allow for broad
scope under high regio- and
stereocontrol. Examples of latestage modification of biologically
relevant scaffolds with functional
allylic groups add further synthetic
value to the developed catalytic
protocol.

Lei Deng, Arjan W. Kleij* and
Weibo Yang*

Page No. – Page No.

Diversity-Orientated
Stereoselective Synthesis
through Pd-Catalyzed
Switchable Decarboxylative C‒
N/C‒S Bond Formation in Allylic
Surrogates