Oxaziridine-Mediated Oxidation Reaction of Thiolates To Give Sulfenates: The First One-Pot Synthesis of Sulfoxides from Thiols

Full text of DOI:10.1021/jo9717604

8
626
J . Org. Chem. 1997, 62, 8626-8627
Sch em e 1a
Oxa zir id in e-Med ia ted Oxid a tion Rea ction
of Th iola tes To Give Su lfen a tes: Th e F ir st
On e-P ot Syn th esis of Su lfoxid es fr om
Th iols
Franck Sandrinelli, St e´ phane Perrio,* and
Pierre Beslin
a
Reagents and conditions: (a) PhSO2NH2, TiCl4, ClCH2CHCl2,
reflux, 14 h, 73%; (b) m-CPBA (100%), CH2Cl2/H2O/K2CO3, rt, 1.5
Laboratoire de Chimie Mol e´ culaire et Thio-organique
h, 84%.
(
6
Associ e´ au CNRS, UMR 6507), ISMRA-Universit e´ de Caen,
boulevard du Mar e´ chal J uin, F-14050 Caen, France
Ta ble 1
Received September 22, 1997
-
-
The oxidation of thiolates (RS ) to sulfenates (RSO )
1
is not a common reaction in organic chemistry and has
been reported in only three papers to date. Further-
2
more, the examples described are too specific for this
reaction to be generally applicable in synthesis.3 This
lack of examples stems from the following reasons: (i)
isolated
entry thiol
R1
R2
R3
R4
sulfoxidea yield (%)
4
sulfenate anions are of limited stability, (ii) a competitive
14a
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3b
3c
3d
3e
3f
H
H
H
H
t-Bu
F
OMe
H
H
H
H
H
H
H
H
CF3
H
H
Me
Et
i-Pr
Bn
Me
Me
Me
Me
4a 1
4a 2
4a 3
89
oxidative pathway leading to symmetrical disulfides may
H
H
H
H
H
H
H
8314b
occur,1 (iii) the oxidizing agents employed up to now,
,5
14b
66
2
,3
4a 4
7914c
m-CPBA and hydrogen peroxide, were not particularly
well suited to this task. Because of this, we reasoned
that a switch to a totally different type of oxidant might
bring about significant improvements. N-Sulfonyl-
oxaziridines are known to convert thiols into sulfenic
acids.6 Since thiolate anions have somewhat greater
nucleophilicity, we thought we might achieve some
interesting results with this class of oxidant. Initial
4b1
70
1
4d
4c1
4d 1
4e1
4f1
85
89
75
71
14e
14f
H
SEt Me
a
The electrophiles employed to introduce the R4 substituent
were MeI (1.1 equiv), EtI (5 equiv), i-PrI (5 equiv), and PhCH2Br
(1.1 equiv).
7
attempts using the classical Davis oxaziridine derived
from benzalhehyde were unsuccessful. We then turned
to the novel ketone-derived oxaziridine 1, in which the
benzenesulfonamide, and titanium tetrachloride were
heated to reflux in 1,1,2-trichloroethane for 14 h, afford-
ing the N-sulfonylimine 2 in 73% crude yield. The crude
material was sufficiently pure to be used subsequently
without further purification. Imine 2 was then converted
8
oxaziridine carbon atom is now a quaternary center with
methyl and tert-butyl substituents. In this paper we wish
to report the results obtained using this oxidant, which
have led to the development of an elegant method for the
generation and subsequent synthetic application of
sulfenate anions.
9
into the corresponding oxaziridine 1 with pure m-CPBA
in a CH Cl /H O biphasic system buffered with K CO .
2 2 2 2 3
The oxaziridine 1 was isolated in 84% yield after recrys-
tallization from hexane and was obtained as a single
geometric isomer, as indicated by the presence, in the
1
13
H and C NMR spectra, of a single set of signals for
both the methyl and tert-butyl substituents. A trans
geometry was unambiguously assigned after analysis of
these spectra and comparison with those of known
oxaziridines10 previously obtained as a mixture of cis/
trans diastereoisomers.
The N-sulfonyloxaziridine 1 was prepared in two steps
as follows (Scheme 1). Equimolar amounts of pinacolone,
The protocol we have developed involves three con-
secutive reactions carried out in one pot (Table 1):
deprotonation of the thiol 3 to generate the corresponding
thiolate, oxidation with oxaziridine 1, and finally reaction
with an alkyl halide to trap the intermediate sulfenate
anion. Although sulfenate ions can act as ambident
(
1) The Chemistry of Sulfenic Acids and their Derivatives-The
Chemistry of Functional Groups; Patai, S., Ed.; Wiley: Chichester,
1
990.
(
2) (a) Heckel, A.; Pfleiderer, W. Tetrahedron Lett. 1983, 24, 5047-
5
1
1
050. (b) Hogg, D. R.; Rashid, M. A. M. J . Chem. Res. (S) 1988, 160-
61. (c) Ishii, A.; Komiya, K.; Nakayama, J . J . Am. Chem. Soc. 1996,
18, 12836-12837.
(3) The oxidation of silver 1,3,6-trimethyllumazine-7-thiolate to the
corresponding silver sulfenate with 1 equiv of H
without description of the conditions and the yield. A sodium
2 2
O has been reported
2a
(8) The use of oxaziridine 1 for the hydroxylation of a â-lactam is
reported in a single paper. Its preparation is not, however, described,
and the reasons for choosing this unusual oxaziridine are not given;
Shimizu, M.; Ishida, T.; Fujisawa, T. Chem. Lett. 1994, 1403-1406.
(9) Derbesy, G.; Harpp, D. N. Sulfur Lett. 1995, 19, 1-10.
(10) (a) J ennings, W. B.; Watson, S. P.; Boyd, D. R. J . Chem. Soc.,
Chem. Commun. 1988, 931-932. (b) J ordan, G. J .; Crist, D. R. Org.
Magn. Reson. 1977, 9, 322-324. Additional details about the assign-
ment of stereochemistry to the oxaziridine 1 are provided as Supporting
Information.
1
9
sulfenate was identified by F NMR spectroscopy in the products from
the reaction of sodium 2-nitro-4-(trifluoromethyl)benzenethiolate with
2
b
0
.5 equiv of H
2
O
2
.
More recently a stable thiophenetriptycene-8-
sulfenic acid has been prepared in 70% yield by oxidation of the
2
c
corresponding sodium thiolate with m-CPBA.
(
4) Weigand, W.; W u¨ nsch, R. Chem. Ber. 1996, 129, 1409-1419.
(5) Hudlicky, M. Oxidations in Organic Chemistry; ACS Monograph
1
86, American Chemical Society: Washington, DC, 1990.
6) (a) Davis, F. A.; Billmers R. L. J . Am. Chem. Soc. 1981, 103,
(
7
5
016-7018. (b) Davis, F. A.; Sheppard, A. C. Tetrahedron 1989, 45,
(11) (a) Crumbie, R. L.; Ridley, D. D. Aust. J . Chem. 1981, 34, 1017-
1026. (b) Bonini, B. F.; Maccagnani, G.; Mazzanti, G.; Zani, P. Gazz.
Chim. Ital. 1990, 120, 115-121. (c) Hogg, D. R.; Robertson, A. J . Chem.
Soc., Perkin Trans. 1 1979, 1125-1128. (d) J ones, D. N.; Kogan, T. P.;
Newton, R. F.; Smith, S. J . Chem. Soc., Chem. Commun. 1982, 589-
591. (e) Refvik, M. D.; Froese, R. D. J .; Goddard, J . D.; Pham, H. H.;
Pippert, M. F.; Schwan, A. L. J . Am. Chem. Soc. 1995, 117, 184-192.
703-5742. In a recent paper a stable sulfenic acid was synthesized
by direct oxidation of a thiol with PhIO, and its X-ray structure and
unique reactivities were revealed: (c) Goto, K.; Holler, M.; Okazaki,
R. J . Am. Chem. Soc. 1997, 119, 1460-1461.
(7) Vishwakarma, L. C.; Stringer, O. D.; Davis, F. A. Org. Synth.
1
988, 66, 203-210.
S0022-3263(97)01760-X CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 25, 1997 8627
nucleophiles by reaction either at sulfur to give sulfoxides
or at oxygen to form sulfenic esters, the sulfoxide 4 should
still be the main, if not sole, product.11 The selective
S-alkylation generally observed is in accordance with the
accepted concepts of hard and soft acids and bases.12
We began by subjecting thiophenol 3a to the deproto-
nation/oxidation/alkylation sequence (Table 1, entries
1, entry 9) in which the oxaziridine oxidized the thiolate
sulfur center without affecting the sulfide group at all.
In contrast, oxidation of the bis-sulfide 5 with the same
oxaziridine gave a complex mixture.15 The major com-
ponents, formed in a 1:1 ratio, were identified as the two
1
mono-sulfoxides 4f and 6.
Summarizing, we have introduced the first efficient
and fairly general method for the oxidation of aromatic
thiolates16 to the corresponding sulfenates. The oxidant
employed is an unusual oxaziridine. This oxidation
reaction, combined with in situ trapping of the sulfenate
that is formed, shows exceptional promise as a convenient
approach to the synthesis of sulfoxides. This methodol-
1
-4). Thiophenol 3a was deprotonated at low temper-
ature with MeLi (1 equiv) in THF to give the correspond-
ing lithium thiolate. Dropwise addition of oxaziridine 1
(1 equiv) at -78 °C resulted in an immediate reaction in
which all the oxidant was consumed according to TLC.
Treatment of the resulting solution with an alkyl halide
followed by hydrolysis with aqueous ammonium chloride
solution gave an extremely clean crude product on
workup, consisting of only two species, the anticipated
sulfoxide 4a and benzenesulfonamide (the imine 2 formed
from the oxidation reaction is cleaved to benzenesulfona-
mide and the volatile pinacolone during hydrolysis).
Benzenesulfonamide was then easily removed by pre-
cipitation from dichloromethane:pentane. The sulfoxides
1
7
ogy is highly competitive with the existing repertoire.
Its advantages include its good to excellent yields, ease
of purification, tolerance of a wide range of substrates,
and high chemoselectivity. Above all it is able to be
performed in one pot from thiols. The classical prepara-
tion of sulfoxides from thiols is carried out in two steps
with the initial formation of the sulfide followed by
oxidation, isolation of the sulfide being necessary to avoid
overoxidation.17 The application of the above methodol-
ogy to the synthesis of optically pure sulfoxides is
currently under investigation along with the reactivity
of the sulfenates toward other electrophiles.
4
a were further purified by column chromatography and
were obtained in good to excellent isolated yields.
A few points relating to the sequence overall are
worthy of note. The oxidation of the thiolate proceeded
smoothly without any evidence of diphenyl disulfide
formation. The requisite temperature is much lower
compared with oxaziridine-mediated oxidations of other
sulfur-containing functional groups, i.e., sulfides or
sulfoxides.6b The transient sulfenate anion was captured
exclusively at sulfur, with no contamination from the
sulfenic ester that is the product of the competing
O-alkylation.13 A single molar equivalent of methyl
iodide or benzyl bromide traps the sulfenate efficiently,
whereas an excess is required with less reactive electro-
philes, e.g. ethyl iodide or isopropyl iodide. It should also
be noted that alkylation could not be achieved with
isopropyl bromide.
Ack n ow led gm en t. We gratefully acknowledge fi-
nancial support from MERS (F. Sandrinelli). We also
thank Andreas Haeuseler and Ulrike M o¨ hler from the
University of W u¨ rzburg for a contribution to this work.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectral data of compounds 1, 2, 4b , 4f , and 6
1
1
reported herein (12 pages).
J O9717604
(14) (a) Weber, J . V.; Schneider, M.; Salami, B.; Paquer, D. Recl.
Trav. Chim. Pays-Bas 1986, 105, 99-102. (b) Hojo, M.; Masuda, R.;
Saeki, T.; Fujimori, K., Tsutsumi, S. Synthesis 1977, 789-791. (c)
Kakarla, R.; Dulina, R. G.; Hatzenbuhler, N. T.; Hui, Y. W.; Sofia, M.
J . J . Org. Chem. 1996, 61, 8347-8349. (d) Benassi, R.; Folli, U.; Iarossi,
D.; Mucci, A.; Schenetti, L.; Taddei, F. J . Chem. Soc., Perkin Trans. 2
1989, 517-522. (e) P e´ rez-Encabo, A.; Perrio, S.; Slawin, A. M. Z.;
Thomas, S. E.; Wierzchleyski, A. T.; Williams, D. J . J . Chem. Soc.,
Perkin Trans. 1 1994, 629-642. (f) Andersen, K. K.; Edmonds, W. H.;
Biasotti, J . B.; Strecker, R. A. J . Org. Chem. 1966, 31, 2859-2861.
(15)
The present reaction has been further extended to a
range of substituted aromatic thiols. The results ob-
tained are summarized in Table 1. In all cases, the
desired sulfoxides 4 were formed and isolated in good to
excellent yield, thus demonstrating compatibility with a
variety of different substituents.
Oxidation of thiol 3f, with an ethylsulfenyl substituent,
led to the isolation in 71% yield of a single sulfoxide 4f
1
,
via a completely chemoselective oxidation reaction (Table
(
12) Pearson, R. G. Hard and Soft Acids and Bases; Sisler, H. H.,
Ed.; Dowden, Hutchinson and Ross: Stroudsburg, 1973.
13) A dramatic influence of the solvent was observed. For example,
mixtures of S- and O-alkylation products were isolated when the
alkylation reaction was carried out in the presence of DMF.
(
(16) Starting with aliphatic thiolates, the expected sulfoxides were
not formed. Investigations on this reaction are currently in progress.
(17) Madesclaire, M. Tetrahedron 1986, 42, 5459-5495.