Iminium Salts from α-Amino Acid Decarbonylation. Application to the Synthesis of Octahydroindoloquinolizines

Article abstract of DOI:10.1021/jo00337a018

Iminium salts, formed regiospecifically by the decarbonylation of tertiary α-amino acids, have been applied to the synthesis of substituted tetrahydro-β-carbolines.In this manner the octahydroindolo<2,3-a>quinolizines 5-8 were prepared.Several useful methods for the synthesis of the requisite tertiary pipecolic acids 1-4 were developed.These include alkylation of secondary α-amino esters with tryptophyl bromide and alkylation of tryptophan methyl ester with α,ω-dibromo esters.Following deprotection, the resulting tertiary α-amino acids were heated in phenylphosphonic dichloride to give the cyclized products in good yield.The presence of other substituents α or β to the basic nitrogen induces stereoselectivity in the ring closure.When this substituent is an α-carboxylic acid, it can be replaced by hydrogen through decarbonaylation followed by reduction of the resulting iminium salt.