Communication
Organic & Biomolecular Chemistry
Notes and references
1 For recent reviews, see: (a) N. Isoherranen, J. D. Lutz,
S. P. Chung, H. Hachad, R. H. Levy and I. Ragueneau-
Majlessi, Chem. Res. Toxicol., 2012, 25, 2285; (b) S. S. Bharate
and S. B. Bharate, ACS Chem. Neurosci., 2012, 3, 248.
2 N. S. Simpkins, Sulfones in Organic Synthesis, Pergamon
Press, Oxford, 1993.
Scheme 3 Reaction of dialkyl zinc reagents with sulfonic chloride.
bromide, 4-biphenylzinc bromide and 3-thienylzinc bromide,
all reacted with aromatic sulfonyl chlorides to give the diaryl
sulfones in good to excellent yields. Sterically hindered aro-
matic zinc reagents, such as 2-chloro-6-(trifluoromethyl)-
phenylzinc(II) chloride, prepared by in situ transformation of
the corresponding lithium reagent with one equivalent of
ZnCl2, did not react with sulfonyl chloride 2a (8e).
3 M. A. Hickner, H. Ghassemi, Y. S. Kim, B. R. Einsla and
J. E. McGrath, Chem. Rev., 2004, 104, 4587.
4 (a) Z. Wu, H. Song, X. Cui, C. Pi, W. Du and Y. Wu, Org.
Lett., 2013, 15, 1270; (b) S. Répichet, C. Le Roux,
P. Hernandez and J. Dubac, J. Org. Chem., 1999, 64, 6479;
(c) J. Marquié, A. Laporterie and J. Dubac, J. Org. Chem.,
2001, 66, 421.
Benzyl sulfones have significant functions in organic syn-
thesis23 and biochemistry.24 These compounds are normally
synthesized from the corresponding benzyl chloride via sulfi-
nate25 or sulfide in multiple steps. In our protocol, benzylic
zinc reagents, easily prepared from benzylic halides with zinc
metal, reacted smoothly with sulfonyl chlorides to give the
corresponding sulfones in moderate to high yields (9a–9h).
Attempts to introduce aliphatic zinc halide reagents into
this protocol failed, presumably owing to the weak nucleophili-
city and strong alkalinity of these organozinc reagents. Neither
aromatic nor aliphatic sulfonyl chlorides gave the corres-
ponding sulfones in acceptable yields. Gratifyingly, diorgano-
zinc reagents showed good efficiency in these reaction
systems. As shown in Scheme 3, primary and secondary dialkyl
zinc reagents (dioctyl Zn and diisopropyl Zn), readily prepared
via the in situ reaction of n-octyl and isopropyl bromide, mag-
nesium turnings and 0.5 equivalent of ZnCl2, reacted readily
to give the corresponding sulfones in good yields.
5 (a) K. Schank, in The Chemistry of Sulfones and Sulfoxides,
ed. S. Patai, Z. Rappoport and C. J. M. Stirling, Wiley,
New York, 1988, ch. 7; (b) G. Yuan, J. Zheng, X. Gao, X. Li,
L. Huang, H. Chen and H. Jiang, Chem. Commun., 2012, 48,
7513; (c) M. Rahimizadeh, G. Rajabzadeh, S. M. Khatami,
H. Eshghi and A. Shiri, J. Mol. Catal. A: Chem., 2010, 323,
59; (d) A. Rostami and J. Akradi, Tetrahedron Lett., 2010, 51,
3501.
6 (a) M. Baidya, S. Kobayashi and H. Mayr, J. Am. Chem. Soc.,
2010, 132, 4796; (b) K. M. Maloney, J. T. Kuethe and
K. Linn, Org. Lett., 2011, 13, 102–105; (c) W. Zhu and
D. Ma, J. Org. Chem., 2005, 70, 2696; (d) S. Cacchi,
G. Fabrizi, A. Goggiamani, L. M. Parisi and R. Bernini,
J. Org. Chem., 2004, 69, 5608; (e) J. M. Baskin and
Z.-Y. Wang, Org. Lett., 2002, 4, 4423; (f) S. Cacchi,
G. Fabrizi, A. Goggiamani and L. M. Parisi, Org. Lett., 2002,
4, 4719–4721; (g) C. Beaulieu, D. Guay, Z. Wang and
D. A. Evans, Tetrahedron Lett., 2004, 45, 3233; (h) M. Bian,
F. Xu and C. Ma, Synthesis, 2007, 2951.
7 (a) A. Kar, I. A. Sayyed, W. F. Lo, H. M. Kaiser, M. Beller and
M. K. Tse, Org. Lett., 2007, 9, 3405; (b) M. L. Kantam,
B. Neelima, B. Sreedhar and R. Chakravarti, Synlett, 2008,
1455; (c) B. P. Bandgar, S. V. Bettigeri and J. Phopase, Org.
Lett., 2004, 6, 2105.
8 (a) N. Umierski and G. Manolikakes, Org. Lett., 2013, 15,
188; (b) S. C. Cullen, S. Shekhar and N. K. Nere, J. Org.
Chem., 2013, 78, 12194.
9 (a) F. Xiao, H. Chen, H. Xie, S. Chen, L. Yang and
G.-J. Deng, Org. Lett., 2014, 16, 50; (b) P. Katrun,
C. Mueangkaew, M. Pohmakotr, V. Reutrakul, T. Jaipetch,
D. Soorukram and C. Kuhakarn, J. Org. Chem., 2014, 79,
1778; (c) S. Liang, R.-Y. Zhang, L.-Y. Xi, S.-Y. Chen and
X.-Q. Yu, J. Org. Chem., 2013, 78, 11874.
Conclusions
In summary, we have developed a new efficient and general
approach for a CuI catalyzed synthesis of alkyl, aryl and hetero-
aryl sulfones bearing various kinds of functional groups. The
sluggish reactivity of organozinc reagents towards sulfonyl
chlorides can be efficiently improved by the addition of CuI
and bidentate chelate ligand, TMEDA. This practical procedure
considerably extends the reactivity scope of organozinc
reagents. In particular, the direct reaction with sulfonyl chlor-
ides allows the expeditious preparation of various sulfones in
high yields.
10 X. Zhou, J. Luo, J. Liu, S. Peng and G.-J. Deng, Org. Lett.,
2011, 13, 1432.
11 (a) H. Fukuda, F. J. Frank and W. E. Truce, J. Org. Chem.,
1963, 28, 1420; (b) H. Gilman and R. E. Fothergill, J. Am.
Chem. Soc., 1929, 51, 3501; (c) Y. Shirota, T. Nagai and
N. Tokura, Tetrahedron, 1967, 23, 639; (d) Y. Shirota,
T. Nagai and N. Tokura, Tetrahedron, 1969, 25,
3193.
Acknowledgements
The authors are grateful for the financial support from the
National Natural Science Foundation of China (no. 21262030
and 20962017) and the Natural Science Foundation of Gansu
Province, China (no. 1107RJZA263).
4298 | Org. Biomol. Chem., 2014, 12, 4295–4299
This journal is © The Royal Society of Chemistry 2014