Finally, the scope of alkenes in the present reaction was exam-
ined (Table 3). Reactions of several a-methylstyrene derivatives
bearing a para-substituted aromatic ring readily proceeded to
give corresponding b-hydroxysulfone compounds 4b–d in good
yields (Entries 2–4). In the case of compound 1c, FeCl3 caused
decomposition or polymerization of the electron-rich olefin, but
it was found that the use of iron phthalocyanine catalyst afforded
b-hydroxysulfone compound 4c (Entry 3). The reaction of styrene
(1e) afforded b-hydroxysulfone compound 4e in moderate yield
by the use of 10 mol% of [Fe(Pc)] catalyst (Entry 5). Other
styrene derivatives 1f–i underwent similar radical reactions to give
corresponding b-hydroxysulfone compounds 4f–i (Entries 6–9).
In the case of alkene 1i, ring opening reaction of the cyclopropyl
group from a resultant radical intermediate was not observed.
Enyne 1j also showed good reactivity in the present reaction
(Entry 10). Unfortunately, reaction of non-conjugated alkene 1k
did not afford a radical addition product (Entry 11). Since radical
additions of sulfonyl radicals are known to be reversible,13 the
generation of a less stable radical from non-conjugated alkene 1k
might be an unfavourable factor in this reaction. The reaction
of trisubstituted alkene 1l was sluggish due to the steric effect
(Entry 12). When ethyl methacrylate (1m) was treated with 2a in
the presence of 20 mol% of [Fe(Pc)] and air, addition of a sulfonyl
radical took place to give b-hydroxysulfone compound 4m (Entry
13).
Notes and references
§ Typical procedure: A mixture of a-methylstyrene (1a) (118.2 mg,
1.0 mmol), p-toluenesulfonylhydrazide (2a) (465.6 mg, 2.5 mmol) and
FeCl3 (16.2 mg, 0.1 mmol) in THF (5 mL) was heated at 65 ◦C under air.
After removal of solvent under reduced pressure, the residue was purified
by silica gel chromatography (hexane–EtOAc, 3 : 1) to give 3a (275.9 mg,
95%) as colourless crystals.
1 N. S. Simpkins, Sulfones in Organic Synthesis, Pergamon Press, Oxford,
1993.
2 Several sulfone compounds have been used as medicines such as an anti-
cancer reagent: K. G. Petrov, Y.-M. Zhang, M. Carter, G. S. Cockerill,
S. Dickerson, C. A. Gauthier, Y. Guo, R. A. Mook Jr., D. W. Rusnak,
A. L. Walker, E. R. Wood and K. E. Lackey, Bioorg. Med. Chem. Lett.,
2006, 16, 4686.
3 M. P. Bertrand and C. Ferreri, in Radicals in Organic Synthesis, Vol. 2
(ed., P. Renaud and M. Sibi), Wiley-VCH, Weinheim, 2001, pp. 485–
504.
4 Representative examples, TsCl: R. P. Nair, T. H. Kim and B. J. Frost,
Organometallics, 2009, 28, 4681; TsBr:; S.-K. Kang, H.-W. Seo and Y.-
H. Ha, Synthesis, 2001, 1321; TsI:; D. C. Craig, G. L. Edwards and C.
A. Muldoon, Tetrahedron, 1997, 53, 6171.
5 Representative examples: (a) D. H. R. Barton, M. S. Csiba and J. C.
Jaszberenyi, Tetrahedron Lett., 1994, 35, 2869; (b) M. Yoshimatsu, M.
Hayashi, G. Tanabe and O. Muraoka, Tetrahedron Lett., 1996, 37, 4161.
6 J.-M. Fang and M.-Y. Chen, Tetrahedron Lett., 1987, 28,
2853.
7 N. Mantrand and P. Renaud, Tetrahedron, 2008, 64, 11860.
8 (a) T. Mochizuki, S. Hayakawa and K. Narasaka, Bull. Chem. Soc.
Jpn., 1996, 69, 2317; (b) S.-F. Wang, C.-P. Chuang, J.-H. Lee and S.-T.
Liu, Tetrahedron, 1999, 55, 2273.
9 (a) T. Taniguchi, Y. Sugiura, H. Zaimoku and H. Ishibashi, Angew.
Chem., Int. Ed., 2010, 49, 10154; (b) T. Taniguchi, H. Zaimoku and H.
Ishibashi, Chem. Eur. J., 2011, DOI: 10.1002/chem.201003060.
10 A recent example for the sulfonation of alkenes: G. M. Schaaf,
S. Mukherjee and A. G. Waterson, Tetrahedron Lett., 2009, 50,
1928.
11 Examples for the synthesis of b-hydroxysulfones: (a) C. Xi, C. Lai, C.
Chen and R. Wang, Synlett, 2004, 1595; (b) N. Chumachenko and P.
Sampson, Tetrahedron, 2006, 62, 4540.
12 C. Chatgilialoglu, L. Lunazzi and K. U. Ingold, J. Org. Chem., 1983,
48, 3588.
In summary, we have developed a new method for the generation
of sulfonyl radicals from sulfonylhydrazide and the synthesis of b-
hydroxysulfone by the addition to alkenes. The reaction was shown
to be catalysed by inexpensive and nontoxic iron compounds, and
the experimental procedure is very simple and safe. The present
reaction will provide new information on the chemistry of sulfonyl
radicals.
This research was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science
and Technology of Japan.
13 V. I. Timokhin, S. Gastaldi, M. P. Bertrand and C. Chatgilialoglu, J.
Org. Chem., 2003, 68, 3532.
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