Alkyl Radical Addition to Aliphatic and Aromatic N-Acylhydrazones Using an Organic Photoredox Catalyst

Abstract

Increased versatility of intermolecular radical addition to imino acceptors via photoredox catalysis is reported. Primary and secondary radicals, generated via visible-light photocatalysis from alkyl biscatecholatosilicates with organocatalyst 4CzIPN, add successfully to both aromatic and aliphatic N-acylhydrazones in the presence of MgCl 2 . With N-benzoylhydrazones, a simple reductive cleavage of the N−N bond of the hydrazine adduct furnishes the free amine. Synthetic utility is exemplified in a synthetic application toward repaglinide, a clinically important hypoglycemic agent.

Organic thermally activated delayed fluorescence (TADF) compounds used in photocatalysis

“…In lieu of carboxylic acids, a number of other precursors have been used to generate carbon-centred radicals via a reductive quenching pathway. These include alkyltrifluoroborates, 174,175 alkyl bis(catecholato)silicates (or other alkyl silicates), 161,[175][176][177][178][179][180] 4-alkyl-1,4-dihydropyridine derivatives (DHPs) 177,181 and a-trimethylsilylamines 175 (Fig. 30), all of which are oxidised via SET by the excited PC.…”

“…31g), 4CzIPN was the only photocatalyst considered, reaching very high yields of 88% during the optimisation experiments. 178 However, in the alkylation of heteroarenes (Fig. 31b, c and i), the identification of the superior photocatalyst is far more substrate dependent.…”

Synthesis of Chiral Amines by C–C Bond Formation with Photoredox Catalysis

“…Cullen and Friestad addressed this issue with a versatile photoredox-catalyzed radical addition to N-benzoylhydrazones (Scheme 41). 85 Oxidation of biscatecholatosilicates in the presence of 4CzIPN (3.51a) gave the corresponding alkyl radicals, and their additions to N-benzoylhydrazones according to the general mechanism of Scheme 39 produced good yields of adducts 4.20 from both aromatic and aliphatic aldimines. This method was also compatible with primary alkyl radicals, and functioned effectively on gram scale.…”

Photoredox Fluoroalkylation of Hydrazones in Neutral and Reductive Modes

“…To the best of our knowledge, no reductive addition of fluorinated radicals to hydrazones leading to hydrazines has been reported (path b). It is noteworthy that visible light induced reductive addition of non‐fluorinated radicals derived from redox‐active esters [14a] or bis(catecholato)silicates [14b,c] to C=N double bond was extensively studied. In those approaches, Hantzsch ester or DIPEA were applied as hydrogen atom donors.…”