CHEMCATCHEM
HIGHLIGHTS
dard conditions and 2.5 mol% 3 (R=Ar=Ph) afforded stilbene
in 98% yield. It was also demonstrated through a crossover-
like experiment that sulfoxide 3 (R=Ar=Ph) was an efficient
source of sulfenate.
Table 1. Scope of phenyl sulfenate-catalyzed stilbene formation.[a]
To establish the catalyst resting state, the reaction conditions
were replicated but at 508C. The reaction was quenched with
water after 30 min to reveal an 87% yield of benzyl phenyl
sulfoxide (1, R=Ar=Ph), indicating that either the sulfoxide or
its anion was the resting state. However, running the reaction
R
X
Yield [%]
R
X
Yield [%]
H
H
Cl
Br
Cl
Br
Br
Cl
Cl
Br
Cl
95
81
84
2-F
2-Me
1-naphthyl
2,6-Cl2
3-Me
3-F
3-CF3
2-pyridyl
Cl
Cl
Cl
Cl
Br
Cl
Br
Cl
73
92
80
88
75[b]
89
68[c]
54[c]
1
in [D8]THF to allow H NMR analysis did not reveal any benzyl
4-Me
4-Me
4-tBu
4-OMe
4-F
62[b]
70[b]
31[b]
81
phenyl sulfoxide. An additional experiment indicated that po-
tassium tert-butoxide was able to deprotonate benzyl phenyl
sulfoxide in organic solution, prompting the conclusion that
the anion of benzyl phenyl sulfoxide was the resting state in
this catalytic cycle.
4-F
4-Cl
66[b]
99
Given that outcome, Walsh and co-workers sought to isolate
the potassium anion of benzyl phenyl sulfoxide.[3] This was
achieved by deprotonation with KCH2Ph and the subsequent
addition of [18]crown-6 to facilitate crystal formation. Although
not vital to the message of the paper, the X-ray structure and
allied DFT calculations identified structural differences between
the neutral sulfoxide and its a-sulfinyl carbanion.
[a] Reaction conditions as indicated in the text. [b] 5mol% precatalyst
loading. [c] Base identity and/or reaction conditions changed.
Generally, reaction yields were within the 50–99% range.
The lone exception (31%) was when the aryl unit was para-
methoxybenzyl, a group that may negatively affect the depro-
tonation step. 2,2’,6,6’-Tetrachlorostilbene was formed in 88%
yield on the 0.1 mmol-scale. This reaction was chosen to evalu-
ate the scalability of the protocol. If 1.37 g (7.0 mmol) of 2,6-di-
chlorobenzyl chloride were subjected to the optimized reac-
tion conditions, 92% yield of the corresponding stilbene was
obtained.
The history of sulfenate chemistry borders on being esoteric,
with some contributions garnering interest from the broader
organic chemistry community. Recent research, and in particu-
lar the current Walsh paper,[3] have given the sulfenate anion
a new cause. The chemistry celebrates the unique character of
sulfenates and assembles their properties with those of sulfox-
ides into a single catalytic cycle, demonstrating what is be-
lieved to be the first use of a sulfenate in catalysis. More im-
portantly, the work leads the charge of sulfenate chemistry to-
wards mainstream usage in organic chemistry.
All of the aforementioned experiments were performed by
using benzyl phenyl sulfoxide as a precatalyst (Scheme 1,
Ar=Ph). However, upon recognition of the role played by this
compound, other sulfoxides were also reasoned to be suitable
precatalysts and were tested for their fit with the chemistry.
Acknowledging that methyl phenyl sulfoxide is less acidic, yet
possesses the requisite features, it was tested with potassium
hydride. Performing the reaction with 5 mol% methyl phenyl
sulfoxide and benzyl chloride as the substrate delivered stil-
bene in 92% yield. Similarly, dibenzyl sulfoxide (10 mol%) fa-
cilitated the conversion of benzyl chloride to stilbene in 92%
with 3 equivalents of potassium bis(trimethylsilyl)amide in THF.
DMSO also served as a suitable precatalyst, albeit with reduced
efficiency. Use of 10 mol% DMSO with 3 equivalents of potassi-
um hydride and benzyl chloride in CPME gave stilbene in 72%
yield.
Keywords: carbanions
·
organocatalysis
·
reaction
mechanisms · stilbenes · sulfur
[3] M. Zhang, T. Jia, H. Yin, P. J. Carroll, E. J. Schelter, P. J. Walsh, Angew.
[4] J. S. O’Donnell, A. L. Schwan, J. Sulfur Chem. 2004, 25, 183–211.
[5] M. C. Aversa, P. Bonaccorsi, D. Madec, G. Prestat, G. Poli in Innovative
Catalysis in Organic Synthesis (Ed.: P. G. Andersson), Wiley-VCH, Wein-
heim, 2012, pp. 47–76.
[8] F. Gelat, J. Jayashankaran, J.-F. Lohier, A.-C. Gaumont, S. Perrio, Org. Lett.
Although the outcomes of the chemistry were consistent
with the proposed catalytic cycle, the authors nonetheless
sought to gather other supportive evidence.[3] For instance, the
butoxide-mediated reaction of equimolar amounts of benzyl
chloride (2, X=Cl) and benzyl phenyl sulfoxide (1, R=Ar=Ph)
gave stilbene in 91% yield and afforded 2% of 1,2-diphenyl-1-
(phenylsulfinyl)ethane (3, R=Ar=Ph). In another experiment,
much like those outlined in the preceding paragraph seeking
other sources of sulfenate, sulfoxide 3 (R=Ar=Ph) was shown
to be an effective precatalyst; it simply entered the catalytic
cycle at a different stage. In that experiment, the use of stan-
Received: October 13, 2014
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