tri-n-butyltin hydride-mediated radical reaction of a 2-iodobenzamide: formation of an unexpected carbon-tin bond

Abstract

metila. A estrutura do produto foi elucidada por meio das espectrometrias de RMN unidimensionais ( 1 H, 13 C e DEPT) e bidimensionais (COSY e HMQC) e confirmada por espectrometria de massas. Foram apresentadas propostas de mecanismos para explicar a formação do derivado organoestanho.The tri-n-butyltin hydride-mediated reaction of methyl 2,3-di-O-benzyl-4-O-trans-cinnamyl-6-deoxy-6-(2-iodobenzoylamino)-α-D-galactopyranoside afforded an unexpected aryltributyltin compound. The structure of this new tetraorganotin(IV) product has been elucidated by 1 H, 13 C NMR spectroscopy, COSY and HMQC experiments and electrospray ionization mass spectrometry (ESI-MS). The formation of this new compound via a radical coupling reaction and a radical addition-elimination process is discussed. Keywords: tetraorganotin, arylstannane, aryl radical cyclization, 2-iodobenzamide IntroductionIn our studies of Bu 3 SnH-mediated radical cyclizations, we have applied unsaturated organohalides to synthesize large-and medium-size heterocycles. [1][2][3][4][5][6][7][8] Most particularly, ortho-iodobenzamides bearing a side allyloxy group have been used to form benzomacrolactams with 11-, 12-and 20-membered ring via regioselective endo aryl radical cyclization. [1][2][3][4][5] In this context, the benzamide methyl 4-Oallyl-2,3-di-O-benzyl-6-deoxy-6-(2-iodobenzoylamino)-α-D-galactopyranoside (1) was found to give the benzomacrolactam 2 owing to 11-endo cyclization in 32% yield. 2To continue these studies, we applied the Bu 3 SnHmediated radical reaction in an attempt to form the benzomacrolactams 3 and/or 4 from methyl 2,3-di-O-benzyl-4-O-trans-cinnamyl-6-deoxy-6-(2-iodobenzoylamino)-α-Dgalactopyranoside (5), a cinnamylated analogue of 1. Despite our knowledge of preferential endo cyclization mode over the exo-mode in macrocyclization reactions, 1-5,9-16 we expected that 10-exo cyclization could also occur due to the higher stability of the benzyl radical. This hypothesis was supported by the observation that precursors with cinnamyl group provided macrocycle intermediates resulting from 10-exo carbocyclization.6 Moreover, the cinnamyl moiety of 5 would generate a new stereogenic center upon 10-exo or 11-endo cyclization, hence the stereoselectivity of the reaction could be evaluated. In fact, the tri-n-butyltin hydridemediated reaction of 5 afforded an unexpected aryltributyltin compound. Results and DiscussionTo prepare the iodobenzamide 5, the C-4 and C-6 hydroxyl groups of methyl α-D-galactopyranoside were protected as benzylidene acetal 17 and the C-2 and C-3 hydroxyl groups were O-benzylated. 18 Removal of the benzylidene group 19 following by regioselective replacement of the hydroxyl group at C-6 by iodine atom, 2,20 substitution 365 Oliveira et al. Vol. 18, No. 2, 2007 of iodine atom by azido group 2,21 and O-cinnamylation of C-4 hydroxyl group 22 gave the methyl 6-azido-2,3-di-O-benzyl-4-O-trans-cinnamyl-6-deoxy-α-D-galactopyranoside (6). Selective reduction of the azido group 23 gave the expected amine 7, which upon treatment w...

Macrolactamas bioativas e síntese de macrociclos por reação de carbociclização radicalar mediada por hidreto de tri-n-butilestanho

“…As diferenças observadas em relação às reações dos análogos nitrogenados 56 e 59 (Esquema 33) foram atribuídas à menor restrição conformacional em 83 e 85, tanto pelo fato de as rotações serem mais restritas nas amidas que nos ésteres, quanto pela possível formação em 56 e 59 de uma ligação de hidrogênio entre o hidrogênio amídico e o oxigênio do grupo aliloxila. 95 Em outros trabalhos realizados [96][97][98][99][100] foram sintetizados dois amidoésteres (88 e 91, Esquema 38) e quatro amidoéteres (94, 97, 99 e 101, Esquema 38) contendo o grupo cinamila como alvo de ataque do radical arila, diferentemente dos trabalhos até então realizados, em que os substratos eram derivados alílicos. Esperava-se que quando submetidos à reação com Bu 3 SnH estes substratos levassem a macrociclos 11-endo (em geral mais favorecidos [66][67][68] ) e/ou 10-exo.…”