Tandem Reactions via Barton Esters with Intermolecular Addition and Vinyl Radical Substitution onto Indole

Abstract

A one-pot initiator-free Barton ester decomposition with tandem radical addition onto alkyl propiolates or phenylacetylene with aromatic substitution of the resultant vinyl radical allows convenient access to new 9-substituted 6,7dihydropyrido[1,2-a]indoles. Propyl radical cyclizations compete when forming the expanded 7,8-dihydro-6H-azepino[1,2a]indole system. 2-Thiopyridinyl S-radical is incorporated into aromatic adducts when using unsubstituted indole-1-alkanoic acid precursors. X-ray crystallography on substitution products allows selectivity of the radical addition onto less reactive internal alkynes to be determined.

Alkenylation of Arenes and Heteroarenes with Alkynes

“…A number of methods − were based on the generation of reactive vinyl radicals by the addition of various free radical species to the acetylene bond. These reactive vinyl radicals are able to attack (hetero)­aromatic rings to afford alkenylation products.…”

A new era for homolytic aromatic substitution: replacing Bu3SnH with efficient light-induced chain reactions

“…The tandem reaction involves fast addition of the intermediate ethyl radical 20 onto alkyl propiolates or phenylacetylene to give vinyl radicals that undergo substitution onto indole. 109 The cyclized (indol-3-yl) radical adduct is trapped by the 2-thiopyridinyl fragment from 19 returning chain carrier radical 20. This is in agreement with Barton's radical chain proposal with rearomatization facilitated by elimination of 2-pyridinethiol.…”

Advances in the Synthesis of Ring-Fused Benzimidazoles and Imidazobenzimidazoles

“…An alternative approach to HAS, is initiator-free, using in situ generated Barton ester intermediates derived from robust and readily accessible carboxylic acid substrates, giving five- to seven-membered alkyl and cyclopropyl radical cyclizations via a chain reaction mechanism ( Scheme 33 b) [ 104 , 109 ]. Most recently, benzimidazo[2,1- a ]isoquinolin-6-ones were prepared by the addition of methyl radicals onto N -methacryloyl-2-phenylbenzimidazoles 30 using di- tert -butyl peroxide (DTBP) initiator ( Scheme 35 ) [ 110 ].…”