Nucleophilic Addition reactions of 2-Aza-allyl anion: Application to the Total Synthesis of Natural Products

Abstract

The thesis entitled “Nucleophilic Addition reactions of 2-Aza-allyl anion: Application to the Total Synthesis of Natural Products’’ is divided into two sections with an appendix. First section of the thesis details the addition of lithium carbanion of 1,1-diphenyl-2-azapentadiene 1 to various ,-unsaturated esters. Conjugate addition reaction proceeded smoothly to afford the -amino esters with excellent diastereoselectivity and regioselectivity. The strategy was applied in the total synthesis of the alkaloid epibatidine and to the formal synthesis of stemona alkaloid stemoamide (Scheme-1). Scheme 1: Addition of the lithium anion of 1 to the unsaturated esters xiii Addition of lithium carbanion of 1,1-diphenyl-2-aza-pentadiene 1 to non-racemic sulfinimines was presented in the second section of thesis. Addition to aryl aldehyde derived sulfinimines furnished the vicinal diamines (-addition products) with moderate to very good diastereoselectivity. Addition to ortho-substituted benzaldehyde derived sulfinimines exhibited preference for the formation of -addition products. Sulfinimines prepared from aliphatic aldehydes always furnished the vicinal diamines with excellent diastereoselectivity and good yield. The formed products were exemplified in the total synthesis of alkaloid epiquinamide (Scheme-2). Scheme 2: Addition of lithium carbanion of 1,1-diphenyl-2-aza-pentadiene to non-racemic sulfinimines xiv Another application of the formed vicinal diamines obtained was illustrated in the synthesis of differently protected 1,2-cyclohexyldiamine. Reduction of imine using NaCNBH3 followed by RCM of the diene gave the substituted cyclohexene which was further elaborated to functionalized 1,2-cyclohexyldiamine. Scheme 3: Synthesis of differently protected 1,2-cyclohexyldiamine. In the appendix of the thesis, enantiospecific synthesis of Amaryllidaceae alkaloid (+)-γlycorane is presented. The synthesis is accomplished starting from chiral pool S-ethyl lactate using iterative Claisen and Overman rearrangement reactions as the key steps (Scheme-4) Scheme 4: Total synthesis of -lycorane from S-ethyl lactate