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Organic & Biomolecular Chemistry
Page 4 of 5
COMMUNICATION
Journal Name
thioether 3ga efficiently. Reaction of keto thioether 1k did not
lead to the desired rearrangement product, but furnished sulfur
ylide 3ka in the 68% yield instead,12 which might result from the
greatly increased stability of sufur ylide 3ka due to the two
electron-withdrawing groups.
Next, migration ability of different groups in thioethers was
further tested, and the results are listed in Table 4. The para-
substituted tert-butyl group and chloride on the phenyl group
Conclusions
DOI: 10.1039/C7OB00277G
In summary, a facile, transition-metal-free method for the
synthesis of multi-substituted -keto thioethers through
Stevens rearrangement has been developed. In these reactions,
successive C-S/C-H/C-C bonds were formed in a one-pot fashion
under mild conditions. The reactions proceed via the generation
of the sulfur ylide intermediates from arynes and simple
monosubstituted
thioethers and allylic thioethers bearing
underwent smooth Stevens rearrangement to furnish multi-
substituted -keto thioethers in moderate to good yields.
-keto thioethers.
A
range of benzyl
(1m and 1o) did not obviously influence the yields of the
-keto groups
rearrangement products. However, the strong electron-
donating methoxyl group on the phenyl group (1n) was
unfavourable for the rearrangement, leading to the desired
product with deceased yield (entry 2). Thioether 1p with bukyl
triphenylmethyl group produced sulfur ylide 3pa, instead of the
rearrangement product.
Application of this method to synthesize biologically active C-S
bond containing compounds is ongoing in our laboratory and
the results shall be reported in due course.
To further explore the potential synthetic utility, the Stevens
rearrangement with allyl thioethers,
-keto alkyl thioethers and
Acknowledgements
-keto phenyl thioethers (Scheme 2) were examined. As
We are grateful for the Fundamental Research Funds for the
Central Universities (No. 0903005203486) and the National
Natural Science Foundation of China (Nos. 21572027 and
21372267).
expected, allyl thioethers (1q-1s) with aryne precursors 2a
under the optimized reaction conditions could be transformed
into the desired products 3qa, 3ra, and 3sa with moderate to
good yields through [2,3]-sigmatropic rearrangement. 2-
(Methylthio)-1-phenylethan-1-one 1t did not result in the
rearrangement product but furnished the sulfur ylide 3ta in 82%
yield. The ethyl thioether 1u and n-butyl thioether 1v led to the
same phenyl substituted product 1w, which could be explained
by an intramolecular Hofmann elimination process.13 No
Notes and references
1
(a) L. A. Damani, Sulfur-Containing Drugs and Related Organic
Compounds: Chemistry, Biochemistry, And Toxicology; Ellis
Horwood, Ltd., Chichester, 1989; Vol. 1, Part B. (b) N. Kharasch,
The Chemistry of Organic Sulfur Compounds, Pergamon,
London, 1996. (c) R. J. Cremlyn, An Introduction to
Organosulfur Chemistry, Wiley, Chichester, 1996. (d)
com/publications/issue/2013/July2013/Top-200-Drugs-of-
2012.
(a) J. M. Vernier, H. El-Abdellaoui, H. Holsenback, N. D. P.
Cosford, L. Bleicher, G. Barker, B. Bontempi, L. Chavez-Noriega,
F. Menzaghi, T. S. Rao, R. Reid, A. I. Sacaan, C. Suto, M.
Washburn, G. K. Lloyd and I. A. McDonald, J. Med. Chem.,
1999, 42, 1684. (b) H. Y. Chen, S, Kim, J. Y. Wu, E. T. Birzin, W.
Chan, Y. T. Yang, J. Dahllund, F. DiNinno, S. P. Rohrer, J. M.
Schaeffer and M. L. Hammond, Bioorg. Med. Chem. Lett., 2004,
14, 2551. (c) M. J. Rospondek, L. Marynowski and M. Gorá,
Org. Geochem., 2007, 38, 1729 and references therein. (d) A.
Kumar, S. Sharma, V. D. Tripathi and S. Srivastava,
Tetrahedron, 2010, 66, 9445.
reaction took place with
-keto phenyl thioether 1w under the
same reaction conditions.
2
3
4
5
(a) R. B. Woodward, I. J. Pachter and M. L. Scheinbaum, J. Org.
Chem., 1971, 36, 1137. (b) R. M. Coates, Angew. Chem. Int. Ed.,
1973, 12, 586. (c) B. M. Trost, T. N. Salzmann and K. Hiroi, J.
Am. Chem. Soc., 1976, 98, 4887. (d) B. M. Trost, Chem. Rev.,
1978, 11, 453. (e) B. M. Trost, Acc. Chem. Res., 1978, 78, 363.
(a) M. Liao and B. Wang, Green Chem., 2007,
9, 184. (b) J. Li, K
Ji, R. Zheng, J. Nelson and L. Zhang, Chem. Commun., 2014, 50
,
4130. (c) A. Cadu, R. A. Watile, S. Biswas, A. Orthaber, P. J. R.
Sjöberg and J. S. M. Samec, Org. Lett., 2014, 16, 5556. (d) R.
M. P. Dias and A. C. B. Burtoloso, Org. Lett., 2016, 18, 3034.
(a) P. Yates, J. Am. Chem. Soc., 1952, 74, 5376. (b) M. A.
Mckervey and P. Ratananukul, Tetrahedron Lett., 1982, 23
,
2509. (c) H. Brunner, K. Wutz and M. P. Doyle, Monatsh.
Chem., 1990, 121, 755. (d) M. P. Doyle and T. Ye, Modern
Catalytic Methods for Organic Synthesis with Diazo
Compounds; Wiley: New York, 1998. (e) X. Zhang, ARKIVOC,
2002, 2003, 84. (f) Y. Z. Zhang, S. F. Zhu, Y. Cai, H. X. Mao and
Q. L. Zhou, Chem. Commun., 2009, 5362.
Scheme 2 Attempted Stevens rearrangement with β-keto allyl
thioethers, β-keto alkyl thioethers and β-keto phenyl thioethers
4 | J. Name., 2012, 00, 1-3
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