Su lfu r Dioxid e Med ia ted On e-P ot, Th r ee- a n d F ou r -Com p on en t
Syn th eses of P olyfu n ction a l Su lfon a m id es a n d Su lfon ic Ester s:
Stu d y of th e Ster eoselectivity of th e En e Rea ction of Su lfu r
Dioxid e
Laure C. Bouchez, Srinivas Reddy Dubbaka, Majris Turks, and Pierre Vogel*
Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL),
BCH, CH-1015 Lausanne-Dorigny, Switzerland
pierre.vogel@epfl.ch
Received J une 7, 2004
The ene reaction of sulfur dioxide with enoxysilanes or with allylsilanes generates silyl sulfinates
that can be brominated (Br2 or NBS) or chlorinated (NCS or Cl2) to produce the corresponding
sulfonyl halides. They react with primary and secondary amines or alcohols to give the corresponding
sulfonamides and sulfonic esters, respectively. The hetero-Diels-Alder addition of sulfur dioxide
to 1-oxy- or 1,3-dioxy-1,3-dienes generates zwitterions that add to enoxysilanes or allylsilanes giving
silyl sulfinates that can be converted in situ into polyfunctional sulfonamides or sulfonic esters.
This realizes quick access to libraries of complicated sulfonamides and sulfonic esters applying
one-pot, three- and four-component methods.
In tr od u ction
shown substantial antitumor activities,3,4 or are caspase-
15 inhibitors.6 The majority of sulfonamides are prepared
from the reaction of sulfonyl chlorides with ammonia and
primary or secondary amines.7 Arenesulfonyl chlorides
are prepared from arenes by electrophilic substitution
with ClSO3H or from arenesulfonic acids by reaction with
PCl5,8 POCl3,9 or COCl2.10 Other methods imply the
reactions of arenediazonium salts with SO2/CuCl2,11 the
oxidation of thioesters12 or sulfenyl chlorides,13 or the
reaction of organolithium14 or organomagnesium15 re-
agents with SO2Cl2 or SO2 + Cl2. Alkanesulfonyl chlo-
rides can be obtained by reaction of the corresponding
The sulfonamides constitute an important class of
drugs (the sulfa drugs), with several types of pharmaco-
logical agents possessing antibacterial, anticarbonic an-
hydrase, diuretic hypoglycemic antithyroid, antihyper-
tensive, antiinflammatory, and antiviral properties.1,2
Recently, structurally novel sulfonamide derivatives have
(1) (a) Navia, M. A. Science 2000, 288, 2132. (b) Mohamed, S. K.
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10.1021/jo049047j CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/25/2004
J . Org. Chem. 2004, 69, 6413-6418
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