Synthesis of 1,2,3,4-Tetrahydroisoquinoline-1-Carboxylic Acid Derivatives Via Ugi Reactions

The three-component Ugi reactions of 3,4-dihydroisoquinolines, isocyanides and acids furnished 2- acyl-N-substituted-1,2,3,4-tetrahydroisoquinoline-1-carboxamides in moderate to good yields. Chiral, nonracemic acids induced only poor diastereoselectivities in the condensations. Hydrolysis of the Ugi carboxamides gave the corresponding 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids, which due to their ready ability to undergo racemization, were obtained as racemic mixtures or with low enantiomeric excesses.