Reactivity of Superbasic Carbanions Generated via Reductive Radical-Polar Crossover in the Context of Photoredox Catalysis.

Photocatalytic reactions involving a reductive radical-polar crossover (RRPCO) generate intermediates with carbanionic reactivity. Many of these proposed intermediates resemble highly reactive organometallic compounds. However, conditions of their formation are generally not tolerated by their isolated organometallic versions and often a different reactivity is observed. Our investigations on their nature and reactivity under commonly used photocatalytic conditions demonstrate that these intermediates are indeed best described as free, superbasic carbanions capable of deprotonating common polar solvents usually assumed to be inert such as acetonitrile, dimethylformamide, and dimethylsulfoxide. Their basicity not only towards solvents but also towards electrophiles, such as aldehydes, ketones, and esters, is comparable to the reactivity of isolated carbanions in the gas-phase. Previously unsuccessful transformations thought to result from a lack of reactivity are explained by their high reactivity towards the solvent and weakly acidic protons of reaction partners. An intuitive explanation for the mode of action of photocatalytically generated carbanions is provided, which enables methods to verify reaction mechanisms proposed to involve an RRPCO step and to identify the reasons for the limitations of current methods.

Defluorodearomatization: A Photocatalytic Birch-Like Reduction That Enables C-C Bond Formation and Provides Access to Unnatural Cannabinoids.

Within the framework of discovery chemistry, polyfluorination remains a synthetic challenge despite its ability to provide useful characteristics, such as a reduction in the number of hydrogen bond donors and metabolic stability. Coupling a reversal of this methodology with photocatalysis has been demonstrated to allow the rapid synthesis of previously difficult or impossible targets by starting with fluorines everywhere and selectively removing or functionalizing them. Herein, we demonstrate a novel method to synthesize 1,4-cyclohexadienes through a dearomative photocatalytic C-C coupling reaction. This allows for access to materials that are orthogonal to the selectivity of the Birch reaction and are more functional-group-tolerant. The reaction also allows the efficient synthesis of polyfluorinated cannabinoids. While the yields are modest, the access to the new chemical space provided by the reaction is unprecedented by any means. The trifluorinated analog of THC, 1-deoxy-1,2,4-trifluoro-THC, is synthesized, demonstrating the importance of discovery chemistry and the ability to explore otherwise unknown structure-activity relationships.

Photosubstitution in Dicyanobenzene-based Photocatalysts.

We report the photosubstitution of one cyano group in dicyanobenzene-based photocatalysts and thermally activated delayed fluorescence (TADF) emitters. The reaction is a general degradation pathway for some widely used organic photocatalysts such as 4CzIPN and suggests that the active photocatalyst in many reactions is likely different from 4CzIPN. On the contrary, photosubstitution is a facile route to diverse highly reducing photocatalysts and blue TADF emitters.