Radical cascades using enantioenriched 7-azabenzonorbornenes and their applications in synthesis

Abstract

Tandem deoxygenation-neophyl-type radical rearrangement-electrophile trapping using xanthates from 7-azabenzonorbornadienes gives 3-exo-substituted 2-aza-5,6-benzonorbornenes, which in some cases undergo isomerisation to (aminomethyl)indenes. The starting xanthates are accessible in good yields and high enantiomeric ratios via asymmetric hydroboration of (aryne/pyrrolederived) 7-azabenzonorbornadienes. Oxidation (using RuO 4 ) and Birch reduction of the 2-aza-5,6-benzonorbornenes provide access to substituted pyrrolidines and tetrahydroindenes, respectively.

Enantioselective Formal Total Synthesis of (−)-Quinagolide

“…The structure of 18 was confirmed by detailed 2D-NMR analysis, and the ring-opening of isoquinuclidine 17 under the Birch reduction conditions could be explained on the basis of the mechanism proposed (see the SI). It is noteworthy to mention that this type of ring-opening of isoquinuclidine under the Birch reduction conditions is the first of its kind and hopefully will find more applications in the context of the total synthesis of alkaloids and drug development.…”