We report herein that 4‐alkyl‐1,4‐dihydropyridines (alkyl‐DHPs) can directly reach an electronically excited state upon light absorption and trigger the generation of C(sp3)‐centered radicals without the need for an external photocatalyst. Selective excitation with a violet‐light‐emitting diode turns alkyl‐DHPs into strong reducing agents that can activate reagents through single‐electron transfer manifolds while undergoing homolytic cleavage to generate radicals. We used this photochemical dual‐reactivity profile to trigger radical‐based carbon–carbon bond‐forming processes, including nickel‐catalyzed cross‐coupling reactions.

We describe an efficient photoredox system, relying on decatungstate/disulfide catalysts, for the hydrofunctionalization of styrenes. In this methodology the use of disulfide as co-catalyst was shown to be crucial for the reaction efficiency. This photoredox system was employed for the hydro-carbamoylation, -acylation, -alkylation and -silylation of styrenes, giving access to a large variety of useful building blocks and high-value molecules such as amides and unsymmetrical ketones from simple starting materials.

The Cu-catalyzed direct difluoroalkylation of aldehyde hydrazones with functionalized difluoromethyl bromides is described. The reaction yields stereodefined α,α–difluoro-β-keto hydrazones under mild conditions and can be carried out at a scale that opens up the possibility of practical applications.

Recent advances in electrophilic trifluoromethylation reactions of carbonyl compounds and their usual surrogates are highlighted with particular focus on copper-catalysed (or mediated) C-CF3 bond forming reactions. Ketones and aldehydes (notably via their enol ether and enamine derivatives) enable electrophilic trifluoromethylation at the α-carbon of the carbonyl compounds, whereas aldehyde N,N-disubstituted hydrazones undergo electrophilic attack of the cationic or radical CF3 species at the azomethine carbon, thus providing an umpolung alternative to nucleophilic trifluoromethylation of carbonyl compounds. A reversal in reactivity is also observed for conjugated systems. While α,β-unsaturated ketones regioselectively incorporate the CF3 moiety at the α-position of the enones, trifluoromethylation occurs preferentially at the olefinic β-carbon of the corresponding hydrazones.

Thec opper-catalyzed C(sp 2 ) À Ht rifluoromethylation of N,N-disubstituted hydrazones using the Tognir eagent is demonstrated to proceed efficiently for aliphatic aldehyde-derived substrates. Thes uccess of the reactions relied on the choice of the N,N-diphenylamino group as the terminal hydrazone amino group where N,N-dialkylamino groups were preferredf or (hetero)aromatic aldehyde-derived substrates.I na ddition,t he trifluoromethylated N-arylhydrazones are shownt ob eideal substrates for Fischer indole synthesis allowing as traightforward,t hree-step access to 2-trifluoromethylindole derivatives from simplea ldehydes.

4-Fluoropyrazoles are accessible in a single step from readily available aldehyde-derived N-alkylhydrazones through double C-H fluoroalkylation with tribromofluoromethane (CBrF). RuCl(PPh) has been proven to be the most efficient catalyst for this transformation when compared to a range of other Cu-, Pd-, or Fe-based catalyst systems.

A palladium-catalyzed C(sp(2))-H difluoromethylation of aldehyde-derived hydrazones using bromodifluoromethylated compounds to afford the corresponding functionalized difluoromethylketone hydrazones has been established. It is proposed that a radical/SET mechanism proceeding via a difluoroalkyl radical may be involved in the catalytic cycle. Applications of the methodology to the synthesis of α,α-difluoro-β-ketoesters and α,α-difluoroketones (RCOCF2 H) have been illustrated.

Here, 4-functionalized pyrazoles have been made accessible in a single step from readily available aldehyde-derived N,N-dialkyl hydrazones and functionalized polyhalomethane derivatives. The process is believed to follow copper-catalyzed cascade C­(sp2)–H haloalkylation/C­(sp3)–H cyclization/aromatization reaction sequences.