Tri-n-butyltin hydride-mediated radical reactions of ortho-and meta-iodobenzamides to synthesize benzomacrolactams: surprising formation of biphenyl compounds from meta-regioisomers

Reactions of methyl 4-O-allyl-2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino) -α-D-galactopyranoside, its gluco epimer, methyl 2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino)- 4-O-(1-pentenyl)-α-D-glucopyranoside and its ortho-regioisomer with tri-n-butyltin hydride were performed in different conditions. Depending on reaction conditions the three meta-iodo isomers gave a surprising amount of biphenyl compounds. The 2-iodo isomer led only to the undesired but expected hydrogenolysis product. No cyclized products were isolated in all the reactions. The structures of the new biphenyl products were elucidated by 1H and 13C NMR spectroscopy, DEPT, COSY, HMQC and HMBC experiments and ESI-MS/MS. Mechanisms for the formation of these new biphenyl derivatives and hypotheses to explain the different outcomes for radical reactions of 3- or 2-iodobenzamides were presented. (author)