Alkylation of N , N -Dibenzylaminoacetonitrile: From Five- to Seven-Membered Nitrogen-Containing Heterocyclic Systems.

The syntheses of several alkaloids and nitrogen-containing compounds including N -Boc-coniine ( 14b ), pyrrolizidine ( 1 ), δ-coniceine ( 2 ), and pyrrolo[1,2 a ]azepine ( 3 ) are described. New C-C bonds in the α position relative to the nitrogen atom were formed by the alkylation of metalated α-aminonitriles 4 and 6a-c with alkyl iodides possessing the requisite size and functionality. In all of the reported cases, the pyrrolidine ring was formed in the aqueous medium through a favorable 5- exo-tet process involving a primary or a secondary amino group and a terminal δ-leaving group. Conversely, the azepane ring was efficiently formed in N , N -dimethylformamide (DMF), as the preferred aprotic solvent, through an unreported 7- exo-tet cyclization process involving a more nucleophilic sodium amide and a terminal mesylate borne by a saturated six carbon chain unit. In this way, we successfully synthesized pyrrolo[1,2 a ]azepane 3 and 2-propyl-azepane 14c in good yields from inexpensive and readily available materials without tedious separation methods.