Vinyl Isocyanates as Useful Building Blocks for Alkaloid Synthesis

Abstract

Vinyl isocyanates are readily available, reactive functionalities that can serve as useful "1,4-dipole" equivalents in a wide-range of cyclization processes. In combination with various electron rich "1,2-dipoles" (i.e. enamines and enolates), they can deliver structurally elaborate six-membered nitrogen heterocycles suitable for conversion into a number of alkaloid targets including benzophenanthridines, phenanthridines as well as pyridone-derived systems. Reactions with "1,1-dipoles" (i.e. alkyl isocyanides and nucleophilic carbenes) afford highly functionalized pyrrolidinebased products that are amenable to further transformation into members of the amaryillidaceae, erythrina and stemona alkaloid families.

Синтез 5-Ацетил-2-Амино-1,4-Диарил-6-Оксо-1,4,5,6-Тетрагидропиридин-3-Карбонитрилов. Ротамерия В Ряду Тетрагидропиридин-3-Карбонитрилов

“…Известно, что природные и синтетические соединения, содержащие 2-пиридоновый фрагмент [1] обладают фармакологическими свойствами, в часности они проявляют антибактериальную [2] и противоопухолевую [3] активность. Ранее нами было исследовано взаимодействие N-ариламидов ацетоуксусной кислоты с различными электрофильными алкенами с целью разработки новых методов синтеза функционально замещенных производных 2-пиридонов [4,5].…”

Rearrangement of an Intermediate Cyclopropyl Ketene in a RhII-Catalyzed Formal [4 + 1]-Cycloaddition Employing Vinyl Ketenes as 1,4-Dipoles and Donor–Acceptor Metallocarbenes

“…We speculated that improved orbital alignment with the migrating C–C bond and a polarized transition state would assuage this kinetic barrier and provide access to the cyclopentene derivatives under relatively mild conditions. Based on seminal contributions by Danheiser and Rigby, we considered exploiting vinyl ketenes as 1,4-dipoles to achieve this result (Scheme b). While their findings demonstrate the utility of vinyl ketenes with nucleophilic carbenes to provide the cyclopentenones via a penultimate 4π-electrocyclic ring closure, we were inspired to pursue the synthetic potential of these relatively underutilized 1,3-diene equivalents with electrophilic metallocarbenes.…”