Radical condensation between benzylic alcohols and acetamides to form 3-arylpropanamides

Abstract

Benzylic alcohols and acetamides are coupled into 3-arylpropanamides by a new radical condensation through the radical anion of the alcohol.

An alternative mode to activate alcohols: application to the synthesis of N-heteroarene derivatives

“…16 5y Would result from the reaction of DMF with the alcoholate 2'y, the methyl N-heteroarene being deprotonated by KO t Bu or the in situ generated potassium dimethyl amide. 17 The formation of the alkyl formate 5y was sometimes observed but in small amounts (< 10 mol% for 5b), starting for example from 1-naphthalenemethanol 2b (Scheme 2, Eq. 2).…”

Atom‐Economic Alk(en)ylations of Esters, Amides, and Methyl Heteroarenes Utilizing Alcohols Following Dehydrogenative Strategies

“…Besides the transition metal catalyzed alkylations, research efforts have also been directed towards the development of metal‐free protocols. It is well known that the main group metal alkoxides catalyze the Meerwein‐Ponndorf‐Verley and Oppenauer redox process which involves the transfer of hydride through a six‐membered cyclic transition state [25] . Madsen et al .…”

“…It is well known that the main group metal alkoxides catalyze the Meerwein-Ponndorf-Verley and Oppenauer redox process which involves the transfer of hydride through a six-membered cyclic transition state. [25] Madsen et al disclosed a radical condensation reaction to synthesize 3arylpropionamide derivatives using KO t Bu as both radical promoter and base (Scheme 20). In a representative example, refluxing a mixture of benzyl alcohol (1 mmol) and N,N-dimethyl acetamide (2 mmol) in mesitylene for 12 h in presence of KO t Bu (2 eq.)…”

A Journey from June 2018 to October 2021 with N,N-Dimethylformamide and N,N-Dimethylacetamide as Reactants

“…Madsen and Azizi disclosed a transition-metal-free C-alkylation of DMAc with benzylic alcohols, through a reaction mediated by t-BuOK or t-BuONa [146]. Use of 2 equiv.…”

“…No reaction occurred with aliphatic alcohols such as hexan-1-ol and heptan-1-ol. According to the authors, the reaction occurs thanks to the dual role-base and radical initiator-of both bases (that differs from an above hypothesis, see Section 14 [95]) which initiates the formation of radical anion ArCH Madsen and Azizi disclosed a transition-metal-free C-alkylation of DMAc with benzylic alcohols, through a reaction mediated by t-BuOK or t-BuONa [146]. Use of 2 equiv.…”