Synthesis of morphine fragments spiro[benzofuran-3(2H),4'-piperidine] and octahydro-1H-benzofuro[3,2-e]isoquinoline by intramolecular heck reaction

Abstract

As a better alternative to radical cyclization, 5-(2-bromo-6-methoxyphenoxy)-2-methyl-1 ,2,3,4,5,6,7,8-octahydroisoquinoline (2) and its 1-oxo analog 3 underwent Pd-catalyzed intramolecular cyclization to give the tetracyclic (ACNO) morphine fragments 5 and 6 respectively. 4-[(2'-Iodo-6'-methoxyphenoxy)methyl]-1-ethoxycarbonyl-1,2,5,6, -tetrahydropyridine (11) reacted similarly to provide the tricyclic ANO fragment 12 in 70% yield and 45% e.e. when a Pd-(S)-BINAP complex was used as the catalyst.