Communication
RSC Advances
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Scheme 2 a-Cyanation of isochroman.
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Scheme 3 Proposed reaction mechanism.
4 For selected recent examples of oxidative a-cyanation
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A plausible mechanism for the oxidative a-cyanation reac-
tion is shown in Scheme 3. The rst step involves hydride
abstraction from the benzyl position of the protected THIQ to
generate an N-acyliminium ion, and the second step is nucle-
ophilic addition of TMSCN to the N-acyliminium ion to form an
a-amino nitrile. There are two possible mechanisms for the
oxidation step: a hydride transfer mechanism and a single-
electron transfer mechanism, which has been proposed to
form an N-centered radical cation intermediate.5a,5d When we
added 1.5 equiv. of TEMPO to the reaction system, we found
that the result was the same as that when no TEMPO was
added;12 therefore, we infer that no radical intermediate was
formed and that the protected THIQ underwent hydride trans-
fer to generate the N-acyliminium intermediate.
In summary, we developed a highly efficient metal-free a-
cyanation reaction of N-acyl/sulfonyl THIQs that proceeded
under mild conditions. We propose that the oxidation occurred
by means of a hydride transfer mechanism. This reaction
provides a convenient method for the synthesis of a-amino
nitriles and thus will be useful for the preparation of various
natural products and biologically active compounds.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (21132003, 21121002, 21372131), and the Specialized
Research Fund for the Doctoral Program of Higher Education
(20130031110017) for generous nancial support for our
programs.
5 For selected recent examples of a-C–H functionalization
reactions of N-acyl THIQs, see: (a) H. Richter and
O. G. Mancheno, Eur. J. Org. Chem., 2010, 4460; (b)
M. Ghobrial, K. Harhammer, M. D. Mihovilovic and
M. Schnurch, Chem. Commun., 2010, 46, 8836; (c)
M. Ghobrial, M. Schnurch and M. D. Mihovilovic, J. Org.
Notes and references
1 For selected recent reviews of sp3 C–H functionalization, see:
(a) C.-J. Li, Acc. Chem. Res., 2009, 42, 335; (b) J. A. Ashenhurst,
Chem. Soc. Rev., 2010, 39, 540; (c) C. L. Li, B. J. Sun and
Z. J. Shi, Chem. Rev., 2011, 111, 1293; (d) C. S. Yeung and
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