Facile carbon-sulfur bond cleavage in diarylsulfonium ylides: A catalytic sulfur-to-silicon group transfer

Article abstract of DOI:10.1039/c2cc35762c

An unusual cleavage of the non-ylidic carbon-sulfur bond of a sulfonium ylide is reported. The reaction can be catalysed by a variety of palladium(ii) complexes under mild conditions. Preliminary results show that coordination of the ylide to the metal center results in significant structural changes.

Full text of DOI:10.1039/c2cc35762c

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Facile carbon–sulfur bond cleavage in diarylsulfonium
ylides: a catalytic sulfur-to-silicon group transfer†‡
Cite this: Chem. Commun., 2013,
49, 4292
Xueliang Huang, Richard Goddard and Nuno Maulide*
Received 8th August 2012,
Accepted 10th September 2012
DOI: 10.1039/c2cc35762c
www.rsc.org/chemcomm
An unusual cleavage of the non-ylidic carbon–sulfur bond of a
sulfonium ylide is reported. The reaction can be catalysed by a
variety of palladium(II) complexes under mild conditions. Prelimin-
ary results show that coordination of the ylide to the metal center
results in significant structural changes.
Scheme 2 Discovery of a catalytic aryl–sulfur bond cleavage and transfer.
Sulfonium ylides are classical textbook reagents for three-membered
We recently reported a simple synthesis of diphenyl sulfonium
ring formation reactions,1 and have recently been the subject of ylides by a new concept of ‘‘ylide transfer’’.5 While investigating the
renewed attention as potential carbene donors to a metal promoter.2 reactivity towards metal catalysts of some of the products that can
Such carbene transfers are thought to occur either directly, by release be obtained by that methodology,6 we have discovered that an
of the corresponding neutral sulfide upon interaction with a metal unusual cleavage of the sulfur–aryl bond takes place through
catalyst, or by a ‘‘rebound’’ type mechanism of nucleophilic attack to palladium catalysis (Scheme 2). In the event, exposure of indole-
an activated carbon center followed by leaving group expulsion derived diphenylsulfonium ylide 1a to 20 mol% of palladium(II)
(Scheme 1a).3 In contrast, to the best of our knowledge, there is acetate in the presence of phenyldimethylsilane as a reducing agent
no report on the catalytic activation of the non-ylidic carbon–sulfur generated 3-(phenylsulfanyl)indole 3a in 57% yield along with
bond of a sulfonium ylide (Scheme 1b).4 Herein, we describe a diphenyldimethylsilane (as detected by GC-MS).7,8
facile catalytic carbon–sulfur bond cleavage of diarylsulfonium
Subsequent optimisation studies revealed the necessity of a
ylides, which we believe constitutes an unprecedented reactivity palladium(II) salt as a catalyst and the superior performance of
mode of these reagents.
silanes as reducing agents. As depicted in Table 1, the reaction
can take place in various solvents. In particular, clean reactions
proceeding at reasonable rates were observed when acetic acid was
used as the reaction medium (entry 4). In contrast, changing the
solvent to ethyl acetate resulted in fast formation of sulfide 3a
together with other unidentified products (entry 8). The reaction
can be catalysed by diverse palladium(II) sources (entries 9, 10, 11
and 13), though complexes bearing bidentate ligands resulted in
lower efficiency (entry 12). We eventually found that the use of a
cationic palladium(II) source (the complex (CH3CN)4Pd(BF4)2) in the
presence of acetic acid led to very high reproducible yields of the
dearylated product 3a in a short reaction time (entries 14 and 15).
We therefore took the optimised conditions for further studies
(Table 1, entry 15). As portrayed in Scheme 3, this dearylation has
a broad scope among most of the indole and pyrrole ylides
examined,9 and tolerates electron-rich and electron-poor substitu-
ents (cf. 3a to 3h). Interestingly, this palladium-catalysed reaction
leaves an aromatic bromide untouched (cf. 3g).
Scheme 1 Different reactivities of sulfonium ylides.
¨
Max-Planck-Institut fur Kohlenforschung, Kaiser-Wilhelm-Platz 1,
¨
45470 Mulheim an der Ruhr, Germany. E-mail: maulide@mpi-muelheim.mpg.de;
Tel: +49-208-306-2450
† This article is part of the ChemComm ‘Emerging Investigators 2013’ themed
issue.
It is also possible to effect dearylation of carbonyl-substituted
ylides, leading formally to the products of a-sulfenylation of the
parent active methylene compounds (Scheme 4).10
‡ Electronic supplementary information (ESI) available: Experimental, X-ray
crystallography data and NMR. CCDC 894535. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/c2cc35762c
c
4292 Chem. Commun., 2013, 49, 4292--4294
This journal is The Royal Society of Chemistry 2013

View Article Online
Communication
ChemComm
Table 1 Initial discovery and optimisation of conditions
Entry
Solvent
Catalyst
x
Time/h
Yielda (%)
1
2
3
4
5
6
7
8
PhMe
Acetone
MeOH
AcOH
DMF
PhH
DCE
AcOEt
AcOH
AcOH
AcOH
AcOH
AcOH
AcOEt
AcOEt
AcOEt
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PhCN)2Cl2
(Ph3P)2PdCl2
(CH3CN)4Pd(BF4)2
dpppPdCl2
Pd(CH3CN)2Cl2
(CH3CN)4Pd(BF4)2
(CH3CN)4Pd(BF4)2
(CH3CN)4Pd(BF4)2
20
20
20
20
20
20
20
20
20
20
20
20
20
20
10
5
20
36
24
24
14
14
12
1
24
24
24
24
13
1
57
27
30
70b
56
62
72
68
64
67
74
31
83
81b
81b
91b
Scheme 5 Isotope labelling experiments.
9
10
11
12
13
14c
15c
16c,d
1
1
Scheme 6 Studies on alternative reducing reagents, aPhenylboronic acid pina-
col ester can be detected by GC-MS through comparison with an authentic
sample.
a
NMR yields determined using CH2Br2 as the internal standard.
b
c
d
Isolated yield. 10 equiv. of acetic acid were added. The reaction
was carried out under air.
normal hydrosilane with added deuterated acetic acid provided
63% deuterium incorporation at the indole nitrogen (Scheme 5b).
It was also established through a series of background experi-
ments that the reaction does not proceed in the absence of either
the metal catalyst or the silane 2a. Interestingly, other hydride
donors are also viable for this transformation. When 2 equivalents
of pinacolborane 2b were employed (Scheme 6a), the sulfenyl
indole 3a was obtained in good yield. Even formic acid 2c11can
be used, although this requires a longer time (Scheme 6b).
In addition, mixing sulfonium ylide 1a with Pd(OAc)2 and
LiCl led to the isolation of a stable 2 : 1 complex as shown in
Scheme 7, in which a Pd(II) centre is coordinated to the imino
indole fragment of the sulfonium ylide (in its neutral form).‡ There
are important geometrical differences between the structure of
sulfonium ylide 1a when it acts as a ligand bound to Pd in 7 and
that of the isolated sulfonium ylide in the crystal of 1a (see the ESI‡
for a tabulated comparison).5 Although the standard uncertainties of
the distances are somewhat high, a distinctive trend is observable.
Scheme 3 Scope of the palladium-catalysed dearylation of diphenyl sulfonium
ylides.
Scheme 4 Palladium-catalysed dearylation of carbonyl-substituted diphenyl-
sulfonium ylides.
From the outset, we were intrigued by the mechanistic
details of this transformation. The use of deuteriosilane as a
reducing agent did not lead to noticeable deuterium incorpora-
tion in the final product (Scheme 5a). In contrast, the use of
Scheme 7 Preparation of complex 7.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 4292--4294 4293

View Article Online
ChemComm
Communication
2004, 37, 611; (d) Y. Tang, S. Ye and X.-L. Sun, Synlett, 2005, 2720;
(e) E. M. McGarrigle, E. L. Meyers, O. Illa, M. A. Shaw, S. L. Riches
and V. K. Aggarwal, Chem. Rev., 2007, 107, 5841.
2 (a) B. M. Trost, J. Am. Chem. Soc., 1966, 88, 1587; (b) P. Mu¨ller,
D. Fernandez, P. Nury and J.-C. Rossier, Helv. Chim. Acta, 1999,
82, 935; (c) M. Gandelman, B. Rybtchinski, N. Ashkenazi,
R. M. Gauvin and D. Milstein, J. Am. Chem. Soc., 2001, 123, 5372;
(d) M. Gandelman, K. M. Naing, B. Rybtchinski, E. Poverenov,
Y. Ben-David, N. Ashkenazi, R. M. Gauvin and D. Milstein, J. Am.
Chem. Soc., 2005, 127, 15265; (e) S. A. Stoffregen, M. Heying and
W. S. Jenks, J. Am. Chem. Soc., 2007, 129, 15746.
Scheme 8 Catalytic activity of complex 7.
3 For a review on decomposition of iodonium- and sulfonium ylides,
see: (a) P. Mu¨ller, D. Fernandez, P. Nury and J.-C. Rossier, J. Phys.
Org. Chem., 1998, 11, 321; (b) For metal carbene formation from
sulfonium ylides, see ref. 2a: (c) T. Cohen, G. Herman,
T. M. Chapman and D. Kuhn, J. Am. Chem. Soc., 1974, 96, 5627;
In 7, the NQC1 bond of the indole derived diphenylsulphonium
ylide is longer, the C1–C2 bond shorter, and the C2QS and S–C6
bonds are all longer than in 1a (Scheme 8). This is consistent with a
loss of ylide character in the C2QS bond, a build-up of electron
density on the S atom and a weakening of the S–Ph bonds upon
coordination of 1a to the metal. Similarly, coordination of 1a to the
metal causes the C4–N–C1 and C1–C2–C3 angles in the five-
membered heterocyclic ring to widen and the N–C1–C2 angle to
decrease, supporting this view. The relatively short intramolecular
PdÁ Á ÁO distances of 2.960(4) and 2.996(4) Å to the carbonyl
groups (O1 and O3) indicate that net donation of electron
density from the metal to the sulfonium ylide ligand leaves
the Pd atom positively charged.
This complex is catalytically active, as demonstrated by its
ability to promote dearylation of 10-fold amounts of either 1a
(Scheme 8a) or 5a (Scheme 8b). From a mechanistic point of
view, it is possible that the aforementioned electronic effects
upon coordination favor direct attack of the silane at sulfur,
followed by bond reorganisation to release the product and
regenerate the palladium catalyst.
In summary, we describe an unprecedented palladium-catalysed
C(aryl)–S bond cleavage of diaryl sulfonium ylides that proceeds
under mild conditions with transfer of the aryl moiety from sulfur to
an acceptor silane. This intriguing process, which relies on the use
of palladium(II) salts, leads to the products of formal sulfenylation.
Alternative acceptors such as boranes or even formic acid can be
employed. Mechanistic experiments suggest that the ylide substrate
can serve as a suitable neutral, 2-electron ligand for palladium(II).
Further explorations of this and other unique modes of reactivity of
diphenyl sulfonium ylides are underway.
`
(d) B. Cimetiere and M. Julia, Synlett, 1991, 271; (e) P. Mu¨ller,
D. Fernandez, P. Nury and J.-C. Rossier, Helv. Chim. Acta, 1999,
82, 935; ( f ) S. Kramer and T. Skrydstrup, Angew. Chem., Int. Ed.,
2012, 51, 4681. For metal carbenes generated from diazo
compounds, see: (g) M. P. Doyle, Chem. Rev., 1986, 86, 919.
4 For selected examples on application of the Stevens rearrangement,
see: (a) M. P. Doyle, J. H. Griffin, M. S. Chinn and D. V. Leusen,
J. Org. Chem., 1984, 49, 1917; (b) V. Nair, S. M. Nair, S. Mathai,
J. Liebscher, B. Ziemer and K. Narsimulu, Tetrahedron Lett., 2004,
45, 5759; (c) K. K. Ellis-Holder, B. P. Peppers, A. Y. Kovalevsky and
S. T. Diver, Org. Lett., 2006, 8, 2511; (d) A. J. P. Mortimer, A. E. Aliev,
D. A. Tocher and M. J. Porter, Org. Lett., 2008, 10, 5477; (e) J.-P. Qu,
Z.-H. Xu, J. Zhou, C.-L. Cao, X.-L. Sun, L.-X. Dai and Y. Tang,
Adv. Synth. Catal., 2009, 351, 308.
5 X. Huang, R. Goddard and N. Maulide, Angew. Chem., Int. Ed., 2010,
49, 8979.
6 (a) X. Huang, B. Peng, M. Luparia, L. F. R. Gomes, L. F. Veiros and
N. Maulide, Angew. Chem., Int. Ed., 2012, 51, 8886.
7 For selected examples on sulfenylation of indoles, see: (a) M. Tudge,
M. Tamiya, C. Savarin and G. R. Humphrey, Org. Lett., 2006, 8, 565;
(b) Y.-J. Guo, R.-Y. Tang, J.-H. Li, P. Zhong and X.-G. Zhang, Adv.
Synth. Catal., 2009, 351, 2615; (c) J. S. Yadav, B. V. S. Reddy,
Y. J. Reddy and K. Praneeth, Synthesis, 2009, 1520; (d) X.-L. Fang,
R.-Y. Tang, P. Zhong and J.-H. Li, Synthesis, 2009, 4183; (e) Z. Li,
J. Hong and X. Zhou, Tetrahedron, 2011, 67, 3690; ( f ) D. Huang,
J. Chen, W. Dan, J. Ding, M. Liu and H. Wu, Adv. Synth. Catal., 2012,
354, 2123.
8 B. Marciniec, Hydrosilylation, Advances in Silicon Science,
Springer, 2009.
9 For selected examples on preparation of sulfanyl pyrroles, see:
H. M. Gillis, L. Greene and A. Thompson, Synlett, 2009, 112.
10 M. A. Rashid, N. Rasool, M. Adeel, H. Reinke, C. Fischer and
P. Langer, Tetrahedron, 2008, 64, 3782.
11 For hydrogen transfer from formic acid catalysed by palladium, see:
(a) B. M. Trost and F. D. Toste, J. Am. Chem. Soc., 1996, 118, 6305;
(b) B. M. Trost, F. D. Toste and K. Greenman, J. Am. Chem. Soc., 2003,
125, 4518; (c) R. Nakao, H. Rhee and Y. Uozumi, Org. Lett., 2005,
7, 163; (d) S. K. Pandey, A. E. Greene and J.-F. Poisson, J. Org. Chem.,
2007, 72, 7769; (e) J. M. Brunel, Synlett, 2007, 330; ( f ) R. Shen,
T. Chen, Y. Zhao, R. Qiu, Y. Zhou, S. Yin, X. Wang, M. Goto and
L.-B. Han, J. Am. Chem. Soc., 2011, 133, 17037.
Notes and references
1 (a) B. M. Trost and L. S. Melvin, Sulfur Ylides; Academic Press, New
York, 1975; (b) A.-H. Li, L.-X. Dai and V. K. Aggarwal, Chem. Rev.,
1997, 97, 2341; (c) V. K. Aggarwal and C. L. Winn, Acc. Chem. Res.,
c
4294 Chem. Commun., 2013, 49, 4292--4294
This journal is The Royal Society of Chemistry 2013