Diastereoselective synthesis of cycloalkylamines by samarium diiodide-promoted cyclizations of alpha-amino radicals derived from alpha-benzotriazolylalkenylamines

The condensation of omega-unsaturated aldehydes with benzotriazole and secondary amines affords alpha-benzotriazolylalkenylamines that exist in solution as mixtures of the corresponding benzotriazol-1-yl and benzotriazol-2-yl isomers resulting from their rapid dissociation into iminium cations and the benzotriazolyl anion. The reduction of these adducts with samarium diiodide (SmI2) takes place with formation of the benzotriazolyl anion and alpha-amino alkenyl radicals that undergo 5- or 6-exo-trig cyclizations leading to substituted cycloalkyl- or cycloheteroalkylamines. The presence of an electron-withdrawing substituent in the alkene subunit is required for efficient cyclizations. The formation of cyclopentylamines takes place with unusually high 1,5-cis selectivity (hex-5-enyl radical numbering), and the presence of a 2- or 4-Me substituent also imparts high 1,2- or 1,4-trans stereoinduction, respectively. The corresponding six-membered rings, however, are formed with low diastereoselectivity. Semiempirical calculations performed on model systems suggest that a stabilizing secondary orbital interaction between the amino group and the electron-deficient alkene might in part account for the enhanced cis-selectivity encountered.