Angewandte
Chemie
Rev. 2000, 69, 367; k) H. B. Kagan, P. Diter, Organosulfur Chem.
1998, 2, 1 – 39.
The double inversion organometallic displacement proc-
ess was extended to produce other structurally unique
optically active sulfoxides. Either enantiomer of alkyl–alkyl
sulfoxides can be obtained in excellent yields (Table 2,
entries 1–4). Importantly, mild reagents such as organozinc
[2] a) M. Matsugi, N. Fukuda, Y. Muguruma, T. Yamaguchi, J.
Minamikawa, S. Otsuka, Tetrahedron 2001, 57, 2739 – 2744; b) H.
Cotton, T. Elebring, M. Larsson, L. Li, H. Sorensen, S. Unge,
Tetrahedron: Asymmetry 2000, 11, 3819 – 3825.
[3] H. B. Kagan in Catalytic Asymmetric Synthesis, 2nd ed. (Ed.: I.
Ojima), Wiley-VCH, New York, 2000, chap. 6c.
ꢀ
reagents, cleave the S N bond of either endo-3b or
(2R,4S,5R)-6, thus resulting in high yields. For example,
sterically congested 1-adamantylzinc bromide or 3,5-
dimethyl-1-adamantylzinc bromide can be added to endo-
3b, or (2R,4S,5R)-6 to provide the corresponding sulfinates,
which upon treatment with nBuMgBr or EtMgCl, provided
either enantiomer of the appropriate new sulfoxides in high
yields (Table 2, entries 2 and 3). The success of this method-
ology is also exemplified by the preparation of optically active
alkyl–aryl (Table 2, entries 5 and 6) and aryl–alkyl (Table 2,
entries 7–9) sulfoxides in excellent yields. The one-pot
addition of p-tolylmagnesium bromide followed by EtMgCl
to endo-3 provided only 90% ee. However, a sequential
addition of p-tolylmagnesium bromide, followed by EtMgCl/
CuBr·SMe2 to endo-3 provided increased selectivity (95% ee,
Table 2, entry 7).[7b] Interestingly, enantiopure phenyl p-
tolylsulfoxide can be prepared without any complications
(Table 2, entry 10). As noted in the literature, attempts to
prepare enantiopure tert-butyl(tert-butylsulfinyl)acetate were
unsuccessful.[1f] Gratifyingly, the addition of tert-butylacetate
enolate to (R,S,R)-4b provided enantiopure tert-butyl(tert-
butylsulfinyl)acetate in 93% yield (Table 2, entry 11).[9]
Furthermore, this methodology can be applied to generate
either enantiomer of the novel diethyl (tert-butylsulfinyl)-
methyl-phosphonates in high yields (Table 2, entry 12).[1g]
In conclusion, a new and highly general method for the
preparation of enantiopure sulfoxides from diastereopure N-
sulfonyl-1,2,3-oxathiazolidine-2-oxide derivatives[10] has been
developed. The application of this new and powerful method-
ology for identification of sulfoxide containing novel bio-
logical targets, and sulfoxide derived chiral ligands for
asymmetric catalysis will be reported in due course.
[4] a) P. Metzner, A. Thuillier in Sulfur Reagents in Organic
Synthesis, Academic Press, London, UK, 1994, chap. 2.6.2;
b) H. B. Kagan, F. Rebiere, Synlett 1990, 643 – 650.
[5] a) S. C. Benson, J. K. Snyder, Tetrahedron Lett. 1991, 32, 5885 –
5888; b) W. Oppolzer, O. Froelich, C. Wiaux-Zamar, G. Bernar-
dinell, Tetrahedron Lett. 1997, 38, 2825 – 2828; c) J. K. Whitesell,
M. S. Wong, J. Org. Chem. 1991, 56, 4552 – 4554; d) J. K.
Whitesell, M. S. Wong, J. Org. Chem. 1994, 59, 597 – 601; e) I.
Fernandez, N. Khiar, J. M. Llera, F. Alcudia, J. Org. Chem. 1992,
57, 6789 – 6796; f) H. El Ouazzani, N. Khiar, I. Fernandez, F.
Alcudia, J. Org. Chem. 1997, 62, 287 – 291; g) I. Fernandez, C. S.
Araujo, M. J. Romero, F. Alcudia, N. Khiar, Tetrahedron 2000,
56, 3749 – 3753; h) N. Khiar, C. S. Araujo, F. Alcudia, I.
Fernandez, J. Org. Chem. 2002, 67, 345 – 356; i) J. Posakony,
J. T. Tewson, Synthesis 2002, 859.
[6] Z. Han, D. Krishnamurthy, P. Grover, Q. K. Fang, C. H.
Senanayake, J. Am. Chem. Soc. 2002, 124, 7880 – 7881.
[7] a) The absolute stereochemistry of endo-3 and exo-3 was
unambiguously established by single crystal X-ray analysis;
b) For the detailed experimental procedure, see Supporting
Information; c) As in the case of aminoindanol series, exo
isomer of PMTOO can be obtained in 90% yield (with
exo:endo = 9:1) using 2,6-di-tert-butylpyridine as a base.
[8] Absolute configuration was deduced from the synthetic
Scheme 3, involving two consecutive inversions of configuration
and X-ray analysis of (R,S,R)-4b.
[9] Use of tert-butyl (p-tolylsulfinyl)acetate in asymmetric synthesis,
see G. Solladic, C. Bauder, E. Arce-Dubois, P. Y. Jacope,
Tetrahedron Lett. 2001, 42, 2923 – 2925.
[10] a) Polymer bound aryl N-sulfonyl 1,2,3-oxathiazolidine-2-oxide
derivatives are under investigation; b) The application of
PMTOO 6 in the synthesis of valuable sulfinamides and
polymer-supported sulfinamides are under investigation.
For experimental details and molecular structures of
(2R,4S,5R)-6, endo- and exo-3 see Supporting Information.
Received: November 27, 2002 [Z50644]
Keywords: asymmetric synthesis · chiral auxiliaries · chirality ·
.
sulfoxides
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