Stereoselective bromohydrin formation from β-hydroxy sulfoxides mediated by the pendant sulfoxide

Article abstract of DOI:10.1039/a904420e

Regio- and stereo-selective bromohydrin formation promoted by a neighbouring sulfinyl moiety is disclosed.

Full text of DOI:10.1039/a904420e

Stereoselective bromohydrin formation from b-hydroxy sulfoxides mediated by
the pendant sulfoxide†‡
Sadagopan Raghavan,* M. Abdul Rasheed, Suju C. Joseph and A. Rajender
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India.
E-mail: purush101@hotmail.com
Received (in Cambridge, UK) 2nd June 1999, Accepted 12th August 1999
Table 1 Regio- and stereo-selectivity of bromohydrin formationa
Regio- and stereo-selective bromohydrin formation pro-
moted by a neighbouring sulfinyl moiety is disclosed.
Products
Yield (%)
(anti+syn)
The development of new and efficient methods for regio- and
stereo-selective synthesis of biologically active compounds is
an active area of research.1 Our interest in the synthesis of
polyhydroxylated sulfoxides and sulfides, e.g. Mannostatin A
and B, has focussed initially on the stereoselective introduction
of chiral centres in appropriate acyclic precursors.
b-Hydroxy sulfoxide Anti (C-2/C-3)
Syn (C-2/C-3)
It is well-known that sulfoxides may participate as neigh-
bouring groups in a number of reactions.2 Sulfoxide group
participation in halohydrin formation from cyclic3 and simple
acyclic olefins4 has been demonstrated, but its potential to
produce highly functionalised products with stereochemical
control at two adjacent centres in substituted acyclic systems
remains unexplored. Here we report the formation of bromohy-
drins from acyclic b-hydroxy-g,d-unsaturated sulfoxides
(Scheme 1). The unsaturated b-hydroxy sulfoxide precursors
shown in Table 1 were prepared as an epimeric mixture in
equimolar proportion and good yield5 by condensing the lithium
anion of (R)-(+)-methyl p-tolyl sulfoxide6 1 with the appro-
priate aldehydes7 2 (Scheme 2). The isomeric hydroxy sulf-
oxides [(RS, SC) and (RS, RC)] were separated8 by chromatog-
raphy and their configuration assigned unambiguously by
comparison of coupling constants for the protons directly
bonded to the carbon in the b-hydroxy sulfoxide moiety.9
The unsaturated b-hydroxy sulfoxides were reacted with
NBS and water in toluene at ambient temperature to afford the
bromohydrins in moderate to high stereoselectivity in good
yield. Use of solvents like THF, MeCN and CH2Cl2 were not
satisfactory. The sulfoxide group was envisaged to function as
a pendant nucleophile and attack the intermediate bromonium
ion, resulting in formation of a cyclic sulfonium salt which
could then be hydrolysed by water to afford the bromohydrin
(Scheme 3).4 It is well known that hydrolysis of sulfoxonium
salts proceeds with clean inversion on sulfur. Hence in effect the
configuration on sulfur would get inverted.3,10
a
All reactions were carried out on a 0.25 mmol reaction scale at a
concentration of 0.20 M in toluene in the presence of 1.2 equiv. of NBS and
b
1.7 equiv. of H2O. Only one isomer was observed in the crude NMR
c
spectrum of the product mixture. Ratio of the isomers determined after
separation of the isomers. d 10–25% of the product resulting from non-
participation of the sulfinyl moiety also observed.
As Table 1 indicates, the reaction is general for a variety of
g,d-unsaturated sulfoxides. According to the literature prece-
dent11 the reaction of 6a with NBS is expected to afford 7a as
the predominant product. Contrary to the above expectation the
outcome was a 1+1 mixture of 7a and 8a. The phenyl group in
Scheme 2
Scheme 1
† IICT Communication No. 4301.
‡ Experimental and spectral data for species described in this paper are
available from the RSC web site, see http://www.rsc.org/suppdata/cc/
1999/1845/
Scheme 3
Chem. Commun., 1999, 1845–1846
1845

2 K. Narasaka, Y. Ichikawa and H. Kubota, Chem Lett., 1987, 2139; The
Chemistry of Sulphones and Sulphoxides, ed. S. Patai, Wiley, New
York, 1988, pp. 345–346.
3 F. Montanari, R. Danieli, H. Hogeveen and G. Maccagnani, Tetra-
hedron Lett., 1964, 2685.
the sulfoxides 9a, 9b, 12a and 12b directs nucleophilic attack on
the intermediate bromonium ions to C-4 to afford, regio-
selectively, products from 6-endo opening.12 It is also apparent
that the (RS, RC) isomers react to yield products more
stereoselectively than the corresponding (RS, SC) isomers.
4 D. R. Dalton, V. P. Dutta and D. C. Jones, J. Am. Chem. Soc., 1968, 90,
5468.
1
The stereochemical assignments were made by 13C and H
NMR analysis of the spectra of the acetonides derived from the
bromohydrins. The use of 13C NMR data for acetonides of
1,3-diols and 1,2-diols for predicting their relative configura-
tions has been reported by Rychnovsky and co-workers13 and
Dana and co-workers,14 respectively. The coupling constants of
protons on the carbon bearing the hydroxy and bromine in the
six-membered ring acetonides reveal stereospecific trans addi-
tion to the double bond of 9 and 12.15 There are ample
precedents for overall stereospecific trans addition to the double
bond with respect to the olefin geometry in a similar reaction,
viz. halolactonisation.11 Similarly stereospecific trans addition
to the double bond should be operative with 3 and 6 also. The
sulfoxide group is known to deshield protons in which the SNO
bond and the C–H bond are in a 1,3-parallel orientation.16 The
proton on C-2 of the acetonides derived from 5b, 7b, 8b, 11b
and 13b would occupy a 1,3-parallel orientation, while the
proton on C-2 for the isomers 5a, 7a, 8a, 11a and 13a would be
almost orthogonal to the sulfoxide. A comparison of the
chemical shifts for the protons on C-2 of the isomeric sulfoxides
supports the configuration assigned to sulfur.
5 All new compounds gave satisfactory analytical and spectral data.
6 G. Solladie, J. Hull and A. Girardin, Synthesis, 1987, 173.
7 G. I. Tsuchihashi, S. Iriuchijima and M. Ishibashi, Tetrahedron Lett.,
1972, 4605; N. Kunieda, M. Kinoshita and J. Nokami, Chem Lett., 1977,
289; D. R. Williams, J. G. Phillips, F. H. White and J. C. Huffman,
Tetrahedron, 1986, 42, 3003; S. G. Pyne and G. Boche, J. Org. Chem.,
1989, 54, 2663.
8 The b-hydroxy sulfoxides 3 and 12 were separated as their silyl ethers
followed by cleavage with Bu4NF.
9 M. C. Carreno, T. L. Garcia Ruano, A. M. Martin, C. Pedregal, J. H.
Rodrigues, A. Rubio, J. Sanchez and G. Solladie, J. Org. Chem., 1990,
55, 2120 and references cited therein; C. A. Kingsbury and R. A.
Auerbach, J. Org. Chem., 1971, 36, 1737.
10 A. D. Westwell, M. Thornton Pett and C. M. Rayner, J. Chem. Soc.,
Perkin Trans. 1, 1995, 847; B. M. Trost and M. Fray, Tetrahedron Lett.,
1988, 29, 2163.
11 A. R. Chamberlin, M. Dezube, P. Dussalt and M. C. McMills, J. Am.
Chem. Soc., 1983, 105, 5819.
12 M. M. Midland and R. L. Holtermann, J. Org. Chem., 1981, 46, 1227
and references cited therein; G. Belluci, G. Berti, R. Bianchini, G.
Ingrosso and E. Mastrorilli, Gazz. Chim. Ital., 1976, 106, 955 and
references cited therein.
In conclusion, even though the product distribution often
shows regio- and stereo-selectivity in a predictable way,
striking anomalies are observed which underscore the influence
of the sulfoxide group and its configuration on the outcome of
the reaction. Experiments bearing on the mechanistic reasons
for the observed stereoselectivity will be discussed in a later
paper.
13 S. D. Rychnovsky and D. J. Skalitzky, Tetrahedron Lett., 1990, 31,
945.
14 G. Dana and H. Danechpajouh, Bull. Soc. Chim. Fr., 1980, 395.
15 For instance, the coupling constants for the protons Ha and Hb in 15 is
1.5 Hz, while in 16 it is 9.52 Hz.
Notes and references
16 P. Sohar, Nuclear Magnetic Resonance Spectroscopy, CRC Press,
Florida, 1983, vol. 1, p. 34; A. B. Foster, T. D. Inch, M. H. Qadir and
J. M. Webber, J. Chem. Soc., Chem. Commun., 1968, 1086.
1 G. Helmchen, R. W. Hoffmann, J. Mulzer and E. Schaumann,
Stereoselective Synthesis, Houben-Weyl Methods of Organic Chemistry,
Georg Thieme Verlag, Stuttgart, 1996, Workbench Edition E 21, vols.
1–10.
Communication 9/04420E
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Chem. Commun., 1999, 1845–1846