tri-n-Butyltin Hydride-Mediated Radical Reaction of a 2-Iodobenzamide : Formation of an Unexpected Carbon-Tin Bond

Marcelo T. Oliveira, Maria Auxiliadôra F. Prado,* Rosemeire B. Alves, Amary Cesar, Ricardo J. Alves,b Carla G. Queiroga,b Leonardo S. Santos and Marcos N. Eberlin Departamento de Química, Instituto de Ciências Exatas and Departamento de Produtos Farmacêuticos, Faculdade de Farmácia,Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, 31270-901 Belo Horizonte-MG, Brazil Instituto de Química de Recursos Naturales, Universidad de Talca, P.O. Box 747, Talca Chile

The radical reaction was carried out with slow addition of Bu 3 SnH/AIBN to a benzene solution of 5 and very low concentrations of both 5 and Bu 3 SnH (0.013 mol L -1 ).6][27][28] Two main products were formed in the radical reaction: the unexpected tetraorganotin(IV) compound 8 in 29% yield and the uncyclized reduced product 9 in 27% yield (Scheme 1).
The hydrogenolysis product 9 was readily identified from its 1 H and 13 C NMR data.The structure of 8 required a detailed analysis of the NMR spectra ( 1 H, 13 C and DEPT) and connectivity studies by COSY and HMQC experiments.The NMR spectra indicated the presence of a single aromatic hydrogen (δ 7.63) more deshielded than the others eighteen aromatic hydrogens and five ipso carbons.Two of these ipso carbon atoms show chemical shifts compatibles with aryl carbons bound to tin and ortho to tin 29,30 (δ 139.8 and 145.7).Signals of 3 n-butyl moieties bound to Sn, [29][30][31] cinnamyloxy group, methyl galactopyranoside moiety and benzamide were also observed.Table 1 lists selected data of 1 H and 13 C spectra for iodobenzamide 5, tetraorganotin compound 8 and hydrogenolysis product 9.
The ESI(+)-MS spectrum was also found to be fully compatible with the structure of the organotin product Only two articles that describe the isolation of aryltrin-butyltin compounds, as by-products, from Bu 3 SnHmediated aryl radical cyclization were found in the literature. 32,332][3][4][5] The formation of aryltributyltin compounds is described using other methods. 34,35ne possible rationalization for the formation of the tri-n-butylaryltin compound 8 is via the coupling of the aryl and tri-n-butyltin radicals, since chain termination steps can occur in radical reactions. 27,36Other plausible proposals can not be ruled out.For instance, the formation Scheme 1. Reagents, conditions and yields.i: LiAlH 4 , THF, rt; ii: 2-iodobenzoyl chloride, 10% NaOH (aq.) , CH 2 Cl 2 , rt, 44% (over the steps i and ii); iii: Bu 3 SnH, AIBN, benzene, reflux, 8 29%, 9 27%. of 8 could be also attributed to the aromatic substitution by reaction of the reduced product 9 and the tri-n-butyltin radical in an addition-elimination process. 37he formation of 8, as the main product, by intermolecular reaction(s) was unexpected for us, since the reaction was carried out at low concentration of radicals, either by working at high dilution and by slow addition of Bu 3 SnH.6][27][28] When the addition of Bu 3 SnH/AIBN solution was made over a longer period (2.5 hours instead of 1 h) the yields of 8 and 9 reduced to 20% and 21%, respectively.When the concentration of Bu 3 SnH was reduced to 0.0065 mol L -1 and the addition of the reagents was maintained to 2.5 hours none of 8 was formed and the hydrogenolysis product 9 was obtained in 25% yield.In both experiments none of the cyclized product was isolated.
The absence of cyclization product from 5, in contrast with the radical reaction of 1, can be attributed to the steric hindrance between the phenyl ring of the cinnamyl group and the attacking aryl radical in the preferential endo-mode.Other possible explanation for this would be the generation of aryl radical followed by intramolecular hydrogen-atom transfer from the allyl group to the aryl group with the formation of a stable cinnamyl radical, which undergoes reduction to give 9.

8 .
It shows major ions due to cationized forms of 8, that is, of m/z 906.3898 (m/z 906.3743 calculated for [C 49 H 65 NO 6 Sn + Na] + ) and m/z 922.3260 (m/z 922.3481 calculated for [C 49 H 65 NO 6 Sn + K] + ) with a cluster of isotopologue ions characteristic for the presence of Sn multi-isotope element.