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COMMUNICATION
ChemComm
Darzens-type epoxidation by reaction of 2a with benzaldehyde α-iodination and α-fluorination of sulfones, and the use of CBr4
DOI: 10.1039/C9CC00550A
afforded trans-epoxide
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in excellent yield and in Et2O as reagent-solvent combination instead enabled the
diastereoselectivity,5 and nickel-catalysed cross-coupling development of the first direct and selective α,α-di-bromination
conditions adapted from Fu and co-workers led the formation of sulfones via an unselective polybromination followed by
α-arylsulfone 9
(Scheme 5a).2i Additionally, treatment of α,α-di- controlled reductive de-halogenation. The reactions developed
brominated sulfone 3a with neat household bleach led to the are amenable to gram-scale with similar efficiency, and the
formation of hetero-polyhalogenated product 10, known to products formed are shown to be useful synthetic
have moderate anti-fungal activity, in good yield (Scheme 5b).17 intermediates in various transformations.
In summary, a general, direct and selective base-mediated
α-mono- and α,α-di-bromination of alkylsulfones is reported,
where reagent-solvent halogen bonding is proposed to control
Conflicts of interest
the selectivity via alteration of the effective size of the
electrophilic reagent. The use of Br2 in 1,4-dioxane provided
complete selectivity for the α-mono-brominated products,
presumably through the in situ formation of a Br2•dioxane
complex as sterically congested electrophilic bromine source.
The reaction could be extended to the selective α-chlorination,
There are no conflicts to declare.
Notes and references
1
For reviews, see: (a) The Chemistry of Sulfones and Sulfoxides
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Nucleophilic substitution: (a) M. Catto, O. Nicolotti, F.
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Winiarski, Acc. Chem. Res., 1987, 20, 282 and references
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7
(a) W. Middelbos, J. Strating and B. Zwanenburg, Tetrahedron
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(a) C. Y. Meyers, A. M. Malte and W. S. Matthews, J. Am.
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α-Chloro sulfones can also be prepared by radical chlorination
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therein; (c) M. Makosza, Synthesis, 1991, 103; (d) M. Ma
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and A. Kwast, Tetrahedron, 1991, 47 5001; radical
,
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Tetrahedron Lett., 1989, 30, 6913; (h) G. Filippini, M. Silvi and 10 For a review, see: N. De Kimpe, R. Verhé, in α-Haloketones, α-
P. Melchiorre, Angew. Chem., Int. Ed., 2017, 56, 4447; (i) J.
Choi, P. Martín-Gago and G. C. Fu, J. Am. Chem. Soc., 2014,
136, 12161.
Haloaldehydes and α-Haloimines (Eds.: S. Patai, Z.
Rappoport), Wiley, New York, 1988.
11 See Supporting Information document for details.
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For recent reviews on the Ramberg-Bäcklund rearrangement, 12 (a) O. Hassel and J. Hvoslef, Acta Chem. Scand., 1954, 8, 873;
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(a) J. B. Baudin, G. Hareau, S. A. Julia, R. Lorne and O. Ruel, 13 For recent reviews on halogen bonds, see: (a) G. Cavallo, P.
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,
Selected examples to epoxides: (a) P. F. Vogt and D. F.
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,
,
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Arai and T. Shioiri, Tetrahedron, 2002, 58, 1407; to aziridines: 14 Considering the low propensity of Cl and F to form strong
(e) V. Reutrakul, V. Prapansiri and C. Panyachotipun,
halogen bonds (see ref. 13), the high selectivity observed for
and is likely due to the inherent steric hindrance of the
reagents used rather than reagent-solvent halogen bonding.
(a) J. Ficini and G. Stork, Bull. Soc. Chim. Fr., 1964, 723; (b) G. 15 W. S. Zou, J. Han and W. J. Jin, J. Phys. Chem. A, 2009, 113
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F. Yang, D. Li, B. Qin and X. Ren, RSC Adv., 2014, 4, 969.
6
,
,
5505; (c) N. Suryakiran, T. Srikanth Reddy, V. Suresh, M. 16 Attempts to extend this method to selective α,α-di-iodination,
Lakshman and Y. Venkateswarlu, Tetrahedron Lett., 2006, 47
,
α,α-di-chlorination and α,α-di-fluorination reactions were
unsuccessful. See Supporting Information for details.
4319; (d) N. Suryakiran, P. Prabhakar, T. Srikanth Reddy, K.
Chinni Mahesh, K. Rajesh and Y. Venkateswarlu, Tetrahedron 17 (a) K. M. Borys, M. D. Korzyński and Z. Ochal, Tetrahedron
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4 | Chem. Commun., 2019, 00, 1-3
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