Although alcohols are one of the largest pools of alkyl substrates, approaches to utilize them in cross-coupling and crosselectrophile coupling are limited. We report the use of 1°and 2°alcohols in cross-electrophile coupling with aryl and vinyl halides to form C(sp 3 )− C(sp 2 ) bonds in a one-pot strategy utilizing a very fast (<1 min) bromination. The reaction's simple benchtop setup and broad scope (42 examples, 56% ± 15% average yield) facilitates use at all scales. The potential in parallel synthesis applications was demonstrated by successfully coupling all combinations of 8 alcohols with 12 aryl cores in a 96-well plate.

Strong reducing agents (<−2.0 V vs saturated calomel electrode (SCE)) enable a wide array of useful organic chemistry, but suffer from a variety of limitations. Stoichiometric metallic reductants such as alkali metals and SmI 2 are commonly employed for these reactions; however, considerations including expense, ease of use, safety, and waste generation limit the practicality of these methods. Recent approaches utilizing energy from multiple photons or electron-primed photoredox catalysis have accessed reduction potentials equivalent to Li 0 and shown how this enables selective transformations of aryl chlorides via aryl radicals. However, in some cases, low stability of catalytic intermediates can limit turnover numbers. Herein, we report the ability of CdS nanocrystal quantum dots (QDs) to function as strong photoreductants and present evidence that a highly reducing electron is generated from two consecutive photoexcitations of CdS QDs with intermediate reductive quenching. Mechanistic experiments suggest that Auger recombination, a photophysical phenomenon known to occur in photoexcited anionic QDs, generates transient thermally excited electrons to enable the observed reductions. Using blue light-emitting diodes (LEDs) and sacrificial amine reductants, aryl chlorides and phosphate esters with reduction potentials up to −3.4 V vs SCE are photoreductively cleaved to afford hydrodefunctionalized or functionalized products. In contrast to small-molecule catalysts, QDs are stable under these conditions and turnover numbers up to 47 500 have been achieved. These conditions can also effect other challenging reductions, such as tosylate protecting group removal from amines, debenzylation of benzyl-protected alcohols, and reductive ring opening of cyclopropane carboxylic acid derivatives.

Although alcohols represent one of the largest pools of commercially available alkyl substrates, approaches to di-rectly utilize them in cross-coupling and cross-electrophile coupling are limited. We report the use of alcohols in cross-electrophile coupling with aryl and vinyl halides to form C(sp3)–C(sp2) bonds in a one-pot strategy. This strategy allows the use of primary and secondary alcohols through their very fast (<1 min) in situ conversion to the corre-sponding alkyl bromides with compatible phosphonium activating reagents. The utility of the reaction is exempli-fied by its simple reaction setup, scalability, and broad scope (41 examples, 57% ± 15% ave yield). The reaction can be performed on the benchtop without the need for electro-chemical or photochemical equipment. Finally, translation to standard parallel synthesis techniques is demonstrated by successfully coupling all combinations of 8 alcohols with 12 aryl cores in a 96-well plate using only one (99% cover-age) or two (100% coverage) sets of conditions.

Although alcohols represent one of the largest pools of commercially available alkyl substrates, approaches to di-rectly utilize them in cross-coupling and cross-electrophile coupling are limited. We report the use of alcohols in cross-electrophile coupling with aryl and vinyl halides to form C(sp3)–C(sp2) bonds in a one-pot strategy. This strategy allows the use of primary and secondary alcohols through their very fast (<1 min) in situ conversion to the corre-sponding alkyl bromides with compatible phosphonium activating reagents. The utility of the reaction is exempli-fied by its simple reaction setup, scalability, and broad scope (41 examples, 57% ± 15% ave yield). The reaction can be performed on the benchtop without the need for electro-chemical or photochemical equipment. Finally, translation to standard parallel synthesis techniques is demonstrated by successfully coupling all combinations of 8 alcohols with 12 aryl cores in a 96-well plate using only one (99% cover-age) or two (100% coverage) sets of conditions.

Strong reducing agents (< -2.0 V vs SCE) enable a wide array of useful organic chemistry, but suffer from a variety of limitations. Stoichiometric metallic reductants such as alkali metals and SmI2 are commonly employed for these reactions, however considerations including expense, ease of use, safety, and waste generation limit the practicality of these methods. Recent approaches utilizing energy from multiple photons or electron-primed photoredox catalysis have accessed reduction potentials equivalent to Li0 and shown how this enables selective transformations of aryl chlorides via aryl radicals. However, in some cases low stability of catalytic intermediates can limit turnover numbers. Herein we report the ability of CdS nanocrystal quantum dots (QDs) to function as strong photoreductants and present evidence that a highly reducing electron is generated from two consecutive photoexcitations of CdS QDs with intermediate reductive quenching. Mechanistic experiments suggest that Auger recombination, a photophysical phenomenon known to occur in photoexcited anionic QDs, generates transient thermally excited electrons to enable the observed reductions. Using blue LEDs and sacrificial amine reductants, aryl chlorides and phosphate esters with reduction potentials up to -3.4 V vs. SCE are photo-reductively cleaved to afford hydrodefunctionalized or functionalized products. In contrast to small molecule catalysts, the QDs are stable under these conditions and turnover numbers up to 47500 have been achieved. These conditions can also effect other challenging reductions, such as tosylate protecting group removal from amines, debenzylation of alcohols, and reductive ring-opening of cyclopropanecarboxylic acid derivatives.