Angewandte
Communications
Chemie
Radical Reactions
Hydrosulfonylation Reaction with Arenesulfonyl Chlorides and
Tetrahydrofuran: Conversion of Terminal Alkynes into
Cyclopentylmethyl Sulfones
Abstract: An efficient and simple radical chain reaction to
enynes.[5] A variety of precursors, such as sulfonyl halides,[6]
sulfonyl selenides,[7] sulfonyl azides,[8] and allyl sulfones,[9]
convert terminal alkynes into arenesulfonylmethylcyclopen-
tanes is described. The reaction involves a radical addition– have been used. The use of sulfonyl hydrazides[10] and
translocation–cyclization process and necessitates solely the
use of readily available arenesulfonyl chlorides in tetrahydro-
sulfinates[11] under oxidative conditions has also been
reported. Processes involving the addition of a sulfonyl
radical and a hydrogen atom to give alkenyl or alkylsulfones
(hydrosulfonylation) are much less common and require the
use of metal catalysis.[12]
We report herein a hydrosulfonylation procedure based
on the use of commercially or readily available arenesulfonyl
chlorides and THF as the source of the hydrogen atom, thus
avoiding the use of any dedicated reducing agent. The
reaction has been used to carry out efficient cascade reactions
À
furan. Interestingly, this radical-mediated C H activation
process took place with a high level of retention of config-
uration when an enantiomerically pure starting material was
used.
S
ulfones are important and versatile compounds in organic
synthesis. They are present in natural compounds[1] and
analogues[2] presenting biological activity, such as antifungal,
antibacterial, and anti-HIV activity. Moreover, several bio-
logically active compounds containing a sulfone functional
group are known.[3] Sulfones are also useful building blocks, as
illustrated by the preparation of 26,28-methylene-1-a,25-
dihydroxyvitamin D2, a drug candidate for the treatment of
osteoporosis,[4] on the basis of a Julia olefination process
involving a homochiral phenyl cyclopentylmethyl sulfone
(Scheme 1). The addition of sulfonyl radicals to alkenes is one
involving
a
radical addition–translocation–cyclization
(RATC) process leading to the formation of aryl cyclo-
pentylmethyl sulfones from terminal alkynes.[13,14]
The reaction was observed for the first time during an
attempt to form a cyclopentane derivative through chloro-
sulfonylation of alkyne 1a with para-toluenesulfonyl chloride
and dilauroyl peroxide (DLP) in cyclohexane at reflux
(Scheme 2). In contrast to previously reported radical cas-
Scheme 2. Discovery of the hydrosulfonylation reaction. Tol =tolyl.
Scheme 1. A cyclopentylmethyl phenyl sulfone building block.
of the mildest methods to introduce a sulfonyl group into
a molecule. Interestingly, this approach offers unique oppor-
tunities for cascade reactions involving, for example, the
formation of five-membered-ring systems from dienes and
cades involving the cyclization of dienes[6a,i,11a,15] and eny-
nes[10c,16] or ring opening of vinylcyclopropanes,[17] no trace of
the expected cyclic chlorinated sulfone 3a was observed.
Instead, cyclic compound 2a resulting from hydrosulfonyla-
tion was obtained in 66% yield. A related observation was
made by Quiclet-Sire and Zard two decades ago during the
study of 1,2-xanthate migration in sugar derivatives, which led
finally to an efficient procedure for the preparation of
deoxysugars.[18]
Rapid solvent screening showed that weak-hydrogen-
atom-donor solvents, such as benzene, acetonitrile, and ethyl
acetate, also provided the cyclized product 2a but in lower
yields (Table 1, entries 2–4).[19] 1,4-Dioxane gave results
similar to cyclohexane (Table 1, entries 1 and 5). The yield
of 2a was significantly increased to 81% when THF[20] was
used as the solvent (Table 1, entry 6).
[*] Dr. C. S. Gloor, Prof. P. Renaud
Department of Chemistry and Biochemistry, University of Bern
Freiestrasse 3, 3012 Bern (Switzerland)
E-mail: philippe.renaud@dcb.unibe.ch
Dr. F. DØns
CEISAM UMR CNRS 6230— UFR des Sciences et des Techniques
UniversitØ de Nantes
2 rue de la Houssinire, BP 92208, 44322 Nantes Cedex 3 (France)
E-mail: fabrice.denes@univ-nantes.fr
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
Angew. Chem. Int. Ed. 2017, 56, 13329 –13332
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
13329