Radical and Lewis Acid Mediated Syntheses of Panaginsene, Indole-Fused Azabicyclo[3.3.1]Nonane and Davanoids

Abstract

The thesis contains radical and Lewis acid-mediated syntheses of panaginsene, indole-fused azabicyclo[3.3.1]nonanes, and davanoids. The thesis includes three chapters; chapter-I contains the total synthesis of panaginsene, which is an angularly fused tricyclic molecule having a quaternary carbon center. A Ti(III)-mediated radical cyclization protocol was used to construct the C-C bond, which yielded the quaternary carbon center. The tetra substituted olefin was synthesized by McMurry olefination reaction. Chapter II focused on constructing an indole-fused azabicyclo[3.3.1]nonane core of many alstonia alkaloids, which was synthesized using Sm(II)-mediated radical cyclization reaction. The precursor tetrahydro β-carboline was synthesized by the Pictet-Spengler reaction. A novel radical cyclization protocol was developed to achieve the azabicyclo[3.3.1]nonane core annulated with an indole ring. Chapter III contains a Lewis acid-mediated cycloetherification reaction to construct the tetrahydrofuran core of davanoid natural products. The side chain of davanoids was introduced by Grignard addition on Weinreb amides of davana acid. The non-Evans syn aldol reaction was used to achieve the enantioselective synthesis of the chiral centers of davanoids. Some of the key reactions utilized in this thesis are Ti(III)-mediated radical cyclization, Michael reaction, Sharpless asymmetric epoxidation reaction, HWE reaction, McMurry olefination reaction, Pictet-Spengler reaction, Sm(II)-mediated radical cyclization, Wittig olefination reaction, non Evans syn aldol reaction, Lewis acid-mediated cycloetherification reaction, and Grignard reaction.