Scheme 2 Diastereoselective synthesis of g-hydroxy-a-bromo-sulfones.
(a) PMPSO2(Et4N), DMSO 60 1C. PMP = para-methoxy phenyl.
to avoidance of syn-pentane interactions.8 A g-hydroxy substituent
offers the possibility for various derivatization (ether, ester).
Details for the synthesis of g-hydroxy aliphatic gem-dibromides
10, 12 and 14 (racemic series) are given in the ESI.w Treatment of
compounds 10, 12, and 14 with tetraethylammonium p-methoxy-
benzenesulfinate gave the a-bromosulfones 11, 13 and 15 in good
yields (Scheme 2). The methyl terminated gem-dibromide 10
showed a moderate diastereoselectivity. The isopropyl terminated
substrate 11 gave a very good diastereoselectivity and for the
tert-butyl substituted gem-dibromide 14 only one stereoisomer
was formed. The stereochemical assignment of the main
diastereomer was possible by X-ray structure of the dinitro-
benzoates of compounds 13 and 15 (Scheme 3).
Scheme 3 Conformational bias of gem-dibromide 18 leads via
nucleophile fishing in the transition state 19 to a selective substitution
of Brlk and the formation of a-bromosulfone 20; 21: X-ray structure of
compound 10; 22: part of the X-ray structure of dinitrobenzoate
prepared from compound 13, R2 = COC6H3-3,5-(NO2)2.
sulfinate nucleophile (nucleophile fishing). The stereochemical
control in the preparation of a-bromosulfones shall allow their
use for further synthetic applications.11
Financial support by the DFG and Fonds der Chemischen
Industrie is gratefully acknowledged. The authors thank
R. W. Hoffmann for helpful discussions.
The free hydroxyl group in the g-position is a prerequisite for
the good yields and diastereoselectivities. The corresponding
methyl ethers 16 gave lower yields and nearly no diastereo-
selectivity of the corresponding a-bromosulfones 17.9
Notes and references
1 R. W. Hoffmann, Synthesis, 2004, 2075.
2 G. Ko
Ed. Engl., 1967, 6, 41).
3 R. W. Hoffmann, M. Bewersdorf, K. Ditrich, M. Kruger and
¨
brich, Angew. Chem., 1967, 79, 15 (Angew. Chem., Int.
¨
A possible rationale for the increased reactivity and stereo-
selectivity of g-hydroxy aliphatic gem-dibromides is given in
Scheme 3. All gem-dibromides examined show a preferred confor-
mation 18, which is supported by the X-ray structure of 21 obtained
for dibromide 10 and by earlier observations.8,10 The incoming
sulfinate is precoordinated to the substrate via hydrogen bonding
(nucleophile fishing) which results in an increased reactivity and a
selective nucleophilic substitution of the like-bromine atom. The
main diastereomer a-bromosulfone formed is compound 20. The
increasing diastereoselectivity in the series 10, 12, and 14 can be
explained by their increasing conformational bias.
R. Sturmer, Angew. Chem., 1988, 100, 1232 (Angew. Chem., Int.
¨
Ed. Engl., 1988, 27, 1176).
4 W. M. Ziegler and R. Connor, J. Am. Chem. Soc., 1940, 62, 2596.
5 Dibromide 7 was prepared from heptanal, P(OPh)3 and Br2 in 76%
yield; R. W. Hoffmann and P. Bovicelli, Synthesis, 1990, 657.
6 G. E. Vennstra and B. Zwanenburg, Synthesis, 1975, 519.
7 The elimination side reactions were monitored by NMR
spectroscopy.
8 R. Gottlich, B. Colin Kahrs, J. Kruger and R. W. Hoffmann,
¨
Chem. Commun., 1997, 247.
9 The stereostructural assignment of the g-methoxy a-bromosulfones 17
was possible by comparison of the NMR data of the same compounds
obtained by methyl ether formation of the alcohols 11 and 13.
¨
10 R. W. Hoffmann, H.-C. Stiasny and J. Kruger, Tetrahedron, 1996,
52, 7421.
11 For an alternative stereoselective route to a-bromosulfones: M. B.
Anderson, M. Lamothe and P. L. Fuchs, Tetrahedron Lett., 1991,
32, 4457.
¨
In summary, a differentiation of diastereotopic bromine
atoms in SN2 reactions of gem-dibromides was achieved.
A possible explanation for the observed diastereoselective
formation of a-bromosulfones is a precoordination of the
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 1866–1867 1867