Asymmetric Total Synthesis of (+)-Nominine: Development of a Dual Cycloaddition Strategy for the Synthesis of the Hetisine Alkaloids

Abstract

313 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007.A dual cycloaddition strategy for the synthesis of the hetisine alkaloids has been developed and applied to the asymmetric total synthesis of nominine. The approach relies on an early stage intramolecular aza-1,3-dipolar cycloaddition of a 4-oxidoisoquinolinium betaine with an ene-nitrile dipolarophile and a late stage intramolecular [4+2] Diels-Alder cycloaddition. Also of note is the development of a new method for the preparation of 4-oxidoisoquinolinium betaines. Overall, a 16 step asymmetric synthesis of (+)-nominine was accomplished in 1.3% yield, while (+/-)-nominine was prepared in 15 steps in 6.1% yield.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD