Unexpected conversion of vinyl sulfoxides into carbonyl compounds by means of iodotrimethylsilane

Article abstract of DOI:10.1016/S0040-4039(00)00612-2

The unexpected and previously unknown TMSI-promoted conversion of α,β- unsaturated sulfoxides into carbonyl compounds and disulfides is described. It occurs in good yields under mild conditions. The examples provided support the generality and efficiency of this procedure which acts as a good method for removing the sulfinyl group with the advantage of transforming the vinyl sulfoxides into carbonyl compounds. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00612-2

Tetrahedron Letters 41 (2000) 4441±4445
Unexpected conversion of vinyl sulfoxides into carbonyl
compounds by means of iodotrimethylsilane
Maria C. Aversa,a,* Anna Barattucci,a Paola Bonaccorsi,a Giuseppe Bruno,b
Placido Giannettoa and Manuela Policicchioa
a
Á
Dipartimento di Chimica organica e biologica, Universita degli Studi di Messina, Salita Sperone 31 (vill. S. Agata),
98166 Messina, Italy
b
Á
Dipartimento di Chimica inorganica, Chimica analitica e Chimica ®sica, Universita degli Studi di Messina,
Salita Sperone 31 (vill. S. Agata), 98166 Messina, Italy
Received 28 February 2000; accepted 10 April 2000
Abstract
The unexpected and previously unknown TMSI-promoted conversion of a,b-unsaturated sulfoxides into
carbonyl compounds and disul®des is described. It occurs in good yields under mild conditions. The
examples provided support the generality and eciency of this procedure which acts as a good method for
removing the sul®nyl group with the advantage of transforming the vinyl sulfoxides into carbonyl
compounds. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: carbonyl compounds; desulfurization; iodotrimethylsilane; sulfoxides.
1-Methoxy-3-alkylsul®nylbuta-1,3-dienes such as 1 (Scheme 1) have shown their eciency as
enantiopure partners in asymmetric Diels±Alder cycloadditions.1 The high control exerted by the
sulfoxide chirality on the stereochemistry of the ®nal adducts such as 2, and the easy isolation of
the cycloaddition products in high yields, prompted us to explore their usefulness in asymmetric
synthesis of target molecules. During this work, we observed an unexpected behaviour of iodo-
trimethylsilane (TMSI) which seems to be of general synthetic interest: TMSI was able to convert
a,b-unsaturated sulfoxides into carbonyl compounds in good yields under mild conditions. To
the best of our knowledge, this conversion is without precedent in the literature and we wish to
present herein our ®rst results on this subject.
With the aim of obtaining enantiopure polyhydroxylated molecules from (3R,4S,RS)-4-
(hydroxymethyl)-1-[(1S)-isoborneol-10-sul®nyl]-3-methoxycyclohexene (3) (Scheme 1) we decided
to use TMSI to cleave the O±Me bond following a well-assessed literature procedure.2 The reaction,
which could be performed in an NMR tube and followed by 1H NMR spectroscopy,2 started with
prompt formation of iodine, as indicated by brown colouring of the solution. Compound 3 had
* Corresponding author. Fax: +39-090-393895; e-mail: aversa@imeuniv.unime.it
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00612-2

4442
Scheme 1.
disappeared after 1.5 hours (TLC monitoring). MeOH work-up, followed by column chromatography,
a€orded (R)-4-(hydroxymethyl)cyclohex-2-ene-1-one (4)3 and the more mobile bis-{(1S,2R,4R)-2-
hydroxy-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethyl}disul®de (R*SSR*),4 as the major products of
the reaction. In contrast to the disappointing result of losing the unmasked hydroxy substituent
from the cyclohexene skeleton, the presence of a carbonyl function, which had taken the place of
the alkylsul®nyl moiety, appeared to be an unexpected but remarkable outcome of the TMSI-
induced reaction. It must be noted that alkyl(vinyl)sul®nyl cycloadducts frequently su€er the
problem of ine€ective removal of the chiral auxiliary by classical procedures, such as Raney
nickel desulfurization.5 All these considerations prompted us to explore the reactivity of TMSI
with 1-sul®nylcyclohexene adducts di€erent from 2 and/or its derivative 3. Moreover we studied
the behaviour of simple open-chain vinylsulfoxides in the presence of TMSI, owing to our interest
in testing the generality and eciency of the procedure. Reaction times and yields in products
obtained by TMSI-promoted conversion of vinylsulfoxides into carbonyl compounds are shown
in Table 1.
Table 1
TMSI-promoted conversion of a,b-unsaturated sulfoxides into carbonyl compounds at rt in chloroform
The reaction of cycloadduct 56 with TMSI (Scheme 1) led to compound 6,7 at room temperature
(rt) (entry 2 in Table 1)8 while the polycyclic adduct 79 a€orded a 2:1 diastereomeric mixture of
cyclohexanones 8 and 910,11 under the same conditions (Scheme 2, entry 3 in Table 1). The crystalline
8 and 9 were easily isolated by column chromatography. In our hands their crystals were not

4443
suitable for X-ray di€raction analysis, but the 2,4-dinitrophenylhydrazone derivative 10 gave
X-ray quality crystals by slow evaporation of chloroform solvent, and the results of its di€raction
study are shown in Fig. 1.12,13 When the bornyl group was linked to the sul®nyl function, the
reaction of 119 with TMSI required longer reaction time (entry 4 in Table 1).
Scheme 2.
Figure 1. X-Ray structure (asymmetric unit) of 2,4-dinitrophenylhydrazone 10 showing 30% probability thermal
ellipsoids for non-H atoms, and labelling scheme. The dotted line denotes the intramolecular H-interaction
...
H(3) O(4A)=1.915(7) A, while the dashed lines represent intermolecular interactions between H(3AA) [0.5-x, -y, z-
0.5] and O(5A) [0.5-x, -y, 0.5+z] [2.55(1) A], H(300A) [-x, 0.5+y, 0.5-z] and O(3) [-x, y-0.5, 0.5-z] [2.58(1) A, equivalent of
the interaction between H(300) and O(3A)]

4444
Following the observed transformation of our alkyl(vinyl)sulfoxides 3, 5, 7, 11 into carbonyl
compounds 4, 6, 8 and 9 (Schemes 1 and 2), we decided to test this unusual TMSI reactivity
on substrates where sulfur is linked to a benzene ring, this structural feature being present
in almost all the sulfur-based chiral auxiliaries.14 1-Phenylethenyl(phenyl)sulfoxide (12)15,16 and
phenyl(vinyl)sulfoxide (13) were chosen as substrates for di€erent reasons. The reaction of 12
with TMSI would lead to acetophenone, which can be easily recognized by TLC and isolated.
Phenyl(vinyl)sulfoxide (13) is commercially available together with the corresponding sul®de and
sulfone, so we could perform the same reaction on analogous substrates containing sulfur in
di€erent oxidation states. 1-Phenylethenyl(phenyl)sulfoxide (12) was reacted with TMSI in anhydrous
CHCl3 at RT (entry 5 in Table 1). After MeOH work-up and column chromatography, the
expected acetophenone was obtained together with diphenyldisul®de. The experiments regarding
phenyl(vinyl)-sulfoxide (13), -sul®de and -sulfone were performed on NMR scale in deutero-
chloroform. The phenyl(vinyl)sulfoxide (13) turned completely to acetaldehyde in 96 hours,
no reaction was observed with the sulfone, which remained unchanged even after consecutive
additions of further amounts of TMSI (up to a TMSI/substrate molar ratio 3:1), while the
phenyl(vinyl)sul®de, analogously treated with the same reagent, showed a mixture of products
among which acetaldehyde could not be identi®ed.
The results obtained deserve some comment:
(i) Both nucleophilic sulfur and a sul®nyl oxygen are needed in these conversions of vinyl
sulfoxides into carbonyl compounds. If the former (in sulfones) or the latter (in sul®des)
are absent, the reaction does not occur.
(ii) The steric requirements of the alkyl or aryl substituents directly linked to the sul®nyl
vinyl moiety only a€ect the conversion rate.
In conclusion, we have discovered a mild, ecient and seemingly general method of converting
vinyl sulfoxides into aldehydes or ketones with the advantage of transforming the C±S cleavage
of vinyl sulfoxides, generally not easy to achieve, into the functionalization of the molecule with a
carbonyl group which can be subjected to numerous synthetic transformations. All of these
considerations allow us to anticipate many applications to be developed around this reaction, and
further studies in this direction are now in progress.
References
1. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Jones, D. N. J. Org. Chem. 1997, 62, 4376±4384.
2. Jung, M. E.; Lyster, M. A. J. Org. Chem. 1977, 42, 3761±3765.
3. The analytical data obtained from this material were consistent with those previously reported by Kozmin, S. A.;
Rawal, V. H. J. Am. Chem. Soc. 1997, 119, 7165±7166.
4. Eschler, B. M.; Haynes, R. K.; Kremmydas, S.; Ridley, D. D. J. Chem. Soc., Chem. Commun. 1988, 137±138.
Pyne, S. G.; Dikic, B. J. Chem. Res. (S) 1990, 226±227. Arai, Y.; Matsui, M.; Koizumi, T. J. Chem. Soc., Perkin
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1998, 9, 1577±1587.

4445
7. Analytical and spectroscopic data were fully consistent with the assigned structure. NMR studies of the isolated
compound 6 showed only the enol form, as depicted in Scheme 1.
8. Typical experimental procedure: To a solution of sulfoxide (0.53 mmol) in anhydrous CHCl3 (3 ml), TMSI 97%
(0.8 mmol) was added at rt. The reaction was monitored by TLC. After disappearance of the starting product,
MeOH (30 ml) was added and the reaction mixture stirred for 0.5 h, concentrated under reduced pressure, and
column chromatographed. The disul®de was eluted ®rst in all cases, followed by the carbonyl compound.
9. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Nicolo, F.; Rizzo, S. Tetrahedron: Asymmetry 1999,
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10. Richter, F.; Kratky, C.; Otto, H. H. Sci. Pharm. 1998, 66, 189±198.
11. The analytical data obtained for our sample of 9 were consistent with those previously reported for its racemic
form in Ref. 12.
12. X-Ray data: orange crystals of 10, orthorhombic P212121, a=8.492(2) A, b=11.899(3)
A, c=22.350(4) A, V=2258.2(9) A3, data collection at rt, Z=4, R (obs/all)=0.0603/0.1487, Rw (obs/all)=0.0416/
0.0494, GOF (obs)=1.1803 [obs=1725 for Fꢀ4s(F) on 3974 unique re¯ections with Rint=0.0161; 318
parameters]. Selected bond distances (A) and angles (deg): C(1)±N(2)=1.405(8), C(1)±C(9B)=1.52(1), C(10)±
N(3)=1.346(9), C(100)±N(2)=1.451(8), C(3)±C(3A)=1.50(1), C(3)±N(2)=1.395(9), C(3A)±C(4)=1.536(9), C(3A)±
C(9B)=1.552(9), C(4)±C(5)=1.515(9), C(5)±C(5A)=1.521(9), C(5)±N(1)=1.275(9), C(5A)±C(6)=1.54(1),
C(5A)±C(9A)=1.547(9), C(6)±C(7)=1.52(1), C(7)±C(8)=1.53(1), C(8)±C(9)=1.53(1), C(9)±C(9A)=1.530(9),
C(9A)±C(9B)=1.527(9), N(1)±N(3)=1.393(8), C(1)±C(9B)±C(9A)=115.2(6), C(1)±N(2)±C(100)=121.7(5), C(1)±
N(2)±C(3)=113.6(6), C(10)±N(3)±N(1)=119.1(5), C(100)±N(2)±C(3)=124.7(6), C(20)±C(10)±N(3)=122.8(6), C(3)±
C(3A)±C(4)=108.1(5), C(4)±C(5)±C(5A)=116.0(5), C(4)±C(5)±N(1)=128.3(6), C(5)±N(1)±N(3)=116.4(6),
C(5A)±C(5)±N(1)=115.7(6), C(60)±C(10)±N(3)=120.3(7), C(10)±N(3)±N(1)±C(5)=159.3(6), C(20)±C(10)±N(3)±
N(1)=177.9(6), C(3)±N(2)±C(100)±C(600)=119.7(8).
13. New compounds 3, 6, 8, 10 were obtained in an analytically pure form and characterized by spectroscopic
techniques.
14. For reviews, see: Oae, S.; Uchida, Y. In The Chemistry of Sulphones and Sulphoxides; Patai, S.; Rappoport, Z.;
Stirling, C., Eds. John Wiley & Sons: New York, 1988; Vol. 15, pp. 583±664. Posner, G. H. ibid. pp. 823±849.
Walker, A. J. Tetrahedron: Asymmetry 1992, 3, 961±968. Carreno, M. C. Chem. Rev. 1995, 95, 1717±1760.
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16. Following a well-assessed synthetic strategy (Bell, R.; Cottam, P. D.; Davies, J.; Jones, D. N. J. Chem. Soc.,
Perkin Trans. 1 1981, 2106±2115), we prepared 1-phenylethenyl(phenyl)sulfoxide (12) starting from 2-
cyanoethyl(phenyl)-sulfoxide and phenylacetylene, via the corresponding sulfenic acid.