4708
J. Am. Chem. Soc. 1999, 121, 4708-4709
the presence of binaphthol/Ti(IV) complexes and water. Despite
these efforts, the preparation of enantiomerically pure dialkyl
sulfoxides still remains an uphill task.
Enantioselective Catalytic Oxidation of (Arylthio)- or
(Alkylthio)methylphosphonates as a Route to
Enantiomeric Pure Aryl Alkyl or Dialkyl Sulfoxides
In recent work,13-15 we have introduced the use of carbanionic
leaving groups in the reaction of sulfinyl or phosphinyl derivatives
with organometallic reagents. Focusing the attention on the sulfur
series, we found that halovinyl13,14 and dialkyl methylphospho-
nate15 moieties bound to the sulfur atom behave as leaving groups
in the reaction with organometallic reagents (eq 1).
Maria Annunziata M. Capozzi, Cosimo Cardellicchio,
Giuseppe Fracchiolla, Francesco Naso,* and Paolo Tortorella
Consiglio Nazionale delle Ricerche
Centro di Studio sulle Metodologie
InnoVatiVe di Sintesi Organiche
Dipartimento di Chimica, UniVersita` di Bari
Via Amendola 173, 70126 Bari, Italy
ReceiVed August 10, 1998
Chiral nonracemic sulfoxides are enjoying a deserved popular-
ity among organic chemists due to the number of reactions in
which they can be used for the transfer of chirality.1,2 As a
consequence, the search for new methods leading to enantiomeri-
cally pure sulfoxides represents a synthetic theme of high interest.
Despite these efforts, after almost forty years, the Andersen
procedure is still the method of choice for the preparation of
optically active sulfoxides.2,3 However, the procedure, which is
based upon the reaction of organometallic reagents with a menthyl
arylsulfinate, is practically restricted to the synthesis of diaryl or
aryl alkyl sulfoxides. Menthyl alkanesulfinates, which are neces-
sary for the synthesis of dialkyl sulfoxides, cannot be prepared
with the enantiomerically pure sulfur center. Due to these
drawbacks, in the past decades a variety of approaches have been
introduced. Modified Andersen procedures in which the leaving
group is derived from a chiral auxiliary different from menthol
have been used.4-7
In principle, the enantioselective oxidation of sulfides to
sulfoxides represents an attractive and straightforward route.
Besides biocatalyzed oxidations,8 useful chemical oxidating agents
have been also reported.9-12 Kagan,9 Modena, and Di Furia10 have
utilized a modified Sharpless alkyl hydroperoxide/diethyl tartrate/
Ti(IV) system with or without added water. Uemura11 has adopted
a catalytic procedure based upon the use of hydroperoxides in
We report now the successful enantioselective oxidation of
commercially available diethyl (methylthio)methylphosphonate,
1, diethyl (ethylthio)methylphosphonate, 2, and diethyl (phen-
ylthio)methylphosphonate, 3, with hydroperoxides at room tem-
perature in the presence of catalytic amounts of the complex
formed in situ from Ti(O-i-Pr)4, (+)-1,1′-bi-2-naphthol (BINOL)
and water, with ee values in the range 91->98%. The reaction
produced the corresponding diethyl (methylsulfinyl)methylphos-
phonate, 4,16 diethyl (ethylsulfinyl)methylphosphonate, 5,17 and
diethyl (phenylsulfinyl)methylphosphonate, 6,18 in ee values up
to >98% (Table 1). The ee values of the products 4-6 were
1
determined by H NMR techniques (500 MHz), by using (S)-
BINOL as a chiral solvating agent.19
The suggested mechanism for the enantioselective oxidation
of sulfides in the presence of titanium/BINOL complexes is based
on a combination of an enantioselective oxidation followed by a
kinetic resolution of the formed sulfoxide.11 When the (meth-
ylthio)methylphosphonate 1 was reacted with a strong excess of
oxidant, a high amount of the undesired sulfone was obtained
(entry 1). The addition of a smaller amount of oxidant caused a
decrease in the produced sulfone (entries 2-6), whereas the
enantiomeric purity of the formed sulfoxide remained unchanged.
This result suggests that the oxidation promoted by the catalyst
in our case is a genuine fully enantioselective process, without a
significant contribution from kinetic resolution. The use of tert-
butyl hydroperoxide (entries 1, 2, 4-8) or cumene hydroperoxide
(entry 3) showed no significant difference. Water was found to
have a beneficial, although not fully understood, effect, even in
the large excess required in our reactions. Sulfides 2 and 3 were
oxidized according to the optimized reaction conditions, obtaining
sulfoxides 5 and 6 (entries 7 and 8). The configuration of
sulfinylmethylphosphonates was inferred from the configuration
of the sulfoxides produced in the reaction with organometallic
reagents, which is known to occur with inversion of configura-
tion.15
(1) Walker, A. J. Tetrahedron: Asymmetry 1992, 3, 961-998. Posner, G.
H. Asymmetric synthesis using R-sulfinyl carbanions and â-unsaturated
sulfoxides. In The chemistry of sulphones and sulphoxides; Patai, S.,
Rappoport, Z., Stirling, C., Eds.; John Wiley and Sons: New York, 1988; pp
823-849.
(2) (a) Andersen, K. K. Tetrahedron Lett. 1962, 93-95. (b) Mislow, K.;
Green, M. M.; Laur, P.; Melillo, J. T.; Simmons, T.; Ternay, A. L. J. Am.
Chem. Soc. 1965, 87, 1958-1976. (c) Andersen, K. K. Stereochemistry,
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Wiley and Sons: New York, 1988; pp 55-94. (d) Drabowicz; J.; Kielbasinski,
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(3) Solladie´, G. Synthesis 1981, 185-196.
(4) Evans, D. A.; Faul, M. M.; Colombo, L.; Bisaha, J. J.; Clardy, J.; Cherry,
D. J. Am. Chem. Soc. 1992, 114, 5977-5985.
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The sulfinylmethylphosphonates 4-6 were converted into
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secondary, tertiary, vinyl, and aryl Grignard reagents to give
(7) Kagan, H. B.; Rebiere, F. Synlett 1990, 643-650. Rebiere, F.; Samuel,
O.; Ricard, L.; Kagan, H. B. J. Org. Chem. 1991, 56, 5991-5999.
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N.; Pasta, P.; Ottolina, G. Chem. Commun. 1996, 2303-2307.
(9) (a) Pitchen, P.; Kagan, H. B. Tetrahedron Lett. 1984, 25, 1049-1052.
(b) Pitchen, P.; Dun˜ach, E.; Deshmukh, M. N.; Kagan, H. B. J. Am. Chem.
Soc. 1984, 106, 8188-8193. (c) Zhao, S. H.; Samuel, O.; Kagan, H. B.
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1996, 404-406.
(13) Cardellicchio, C.; Fiandanese, V.; Naso, F. J. Org. Chem. 1992, 57,
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Tetrahedron Lett. 1992, 33, 5121-5124.
(14) Cardellicchio, C.; Fiandanese, V.; Naso, F.; Pietrusiewicz, K. M.;
Wisniewski, W. Tetrahedron Lett. 1993, 34, 3135-3138. Cardellicchio, C.;
Fiandanese, V.; Naso, F.; Pacifico, S.; Koprowski, M.; Pietrusiewicz, K. M.
Tetrahedron Lett. 1994, 35, 6343-6346.
(10) Di Furia, F.; Modena, G.; Seraglia, R. Synthesis 1984, 325-327.
Bortolini, O.; Di Furia, F.; Licini, G.; Modena, G.; Rossi, M. Tetrahedron
Lett. 1986, 27, 6257-6260.
(15) Cardellicchio, C.; Iacuone, A.; Naso, F.; Tortorella, P. Tetrahedron
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(11) Komatsu, N.; Hashizume, M.; Sugita, T.; Uemura, S. J. Org. Chem.
1993, 58, 4529-4533. Komatsu, N.; Hashizume, M.; Sugita, T.; Uemura, S.
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(16) Mikolajczyk, M.; Zatorski, A. Synthesis 1973, 669-671.
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10.1021/ja982836w CCC: $18.00 © 1999 American Chemical Society
Published on Web 05/04/1999