Tropane and Related Alkaloid Skeletons via a Radical [3+3]-Annulation Process

24 November 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

A mild and simple protocol for the synthesis of 8-azabicyclo[3.2.1]octane and 9-azabicyclo[3.3.1]nonane derivatives is described. It provides these valuable bicyclic alkaloid skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials using visible-light photoredox catalysis. This unprecedented annulation process takes advantage of the unique reactivity of ethyl 2-(acetoxymethyl)acrylate as a 1,3-bis radical acceptor and of cyclic N,N-dialkylanilines as radical 1,3-bis radical donors. The success of this process relies on efficient electron transfer processes and highly selective deprotonation of aminium radical cations leading to the key α-amino radical intermediates.

Keywords

alkaloids
synthesis
photoredox catalysis
amines
cascade reaction
aminium radicals
acidity
electrochemistry

Supplementary materials

Title
Description
Actions
Title
Synthesis
Description
Detailed synthetic procedures, characterization of new product, and copies of NMR spectra
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Title
Calculations
Description
DFT calculation of redox potentials and acidity constants
Actions
Title
Electrochemistry
Description
Electrochemical studies of cyclic and bicyclic amines
Actions

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