Carboxylic acids, including amino acids (AAs), have been widely used as reagents for decarboxylative couplings. In contrast to previous decarboxylative couplings that release CO 2 as a waste byproduct, herein we report a novel strategy with simultaneous utilization of both the alkyl and carboxyl components from carboxylic acids. Under this unique strategy, carboxylic acids act as bifunctional reagents in the redox-neutral carbocarboxylation of alkenes. Diverse, inexpensive, and readily available α-AAs take part in such difunctionalizations of activated alkenes via visiblelight photoredox catalysis, affording a variety of valuable but otherwise difficult to access γ-aminobutyric acid derivatives (GABAs). Additionally, a series of dipeptides and tripeptides also participate in this photocatalytic carbocarboxylation. Although several challenges exist in this system due to the low concentration and quantitative amount of CO 2 , as well as unproductive side reactions such as hydrodecarboxylation of the carboxylic acids and hydroalkylation of the alkenes, excellent regioselectivity and moderate to high chemoselectivity are achieved. This process features low catalyst loading, mild reaction conditions, high step and atom economy, and good functional group tolerance, and it is readily scalable. The resulting products are subject to efficient derivations, and the overall process is amenable to applications in the latestage modification of complex compounds. Mechanistic studies indicate that a carbanion is generated catalytically and it acts as the key intermediate to react with CO 2 , which is also generated catalytically in situ and thus remains in low concentration. The overall transformation represents an efficient and sustainable system for organic synthesis, pharmaceutics, and biochemistry.

To determine the reaction pathways at a metal-ligand site in enzymes, we incorporated a terminal thiolate site into a diiron bridging hydride. Trithiolato diiron hydride, (μ-H)Fe(pdt)(dppbz)(CO)(SR) (1(μ-H)) [pdt = 1,3-(CH)S, dppbz = 1,2-CH(PPh), RS = 1,2-CyPCHS)], was synthesized directly by photoassisted oxidative addition of 1,2-CyPCHSH to Fe(pdt)(dppbz)(CO). The terminal thiolate in 1(μ-H) undergoes protonation, affording a thiol-hydride complex [1(μ-H)H]. Placing an acidic SH site adjacent to the Fe-H-Fe site allows intramolecular thiol-hydride coupling and releases H from [1(μ-H)H]. A diiron η-H intermediate in the formation of H is proposed, and is evidenced by the H/D exchange reactions of [1(μ-H)H] with D, DO, and CDOD. Isotopic exchange in [1(μ-D)H] is driven by an equilibrium isotope effect with 2.1 kJ/mol difference in free energy that favors [1(μ-H)D]. [1(μ-H)H] catalyzes H/D scrambling between H and DO or CDOD to produce HD. The reactions based on such a "proton-hydride" model provide insights into the reversible heterolytic cleavage of H by Hases.

Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds. However, general approaches towards carboxylation of carbonyl compounds with CO2 remain scarce. Herein, we report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO2 by using Lewis acidic chlorosilanes as activating/protecting groups. This strategy is general and practical to generate valuable α-hydroxycarboxylic acids. It works well for challenging alkyl aryl ketones and aryl aldehydes, as well as for α-ketoamides and α-ketoesters, the latter two of which have never been successfully applied in umpolung carboxylations with CO2 (to the best of our knowledge). This reaction features high selectivity, broad substrate scope, good functional group tolerance, mild reaction conditions and facile derivations of products to bioactive compounds, including oxypheonium, mepenzolate bromide, benactyzine, and tiotropium. Moreover, the formation of carbon radicals and carbanions as well as the key role of chlorosilanes are supported by control experiments.

Herein a simple, catalyst- and solvent-free system for highly atom-economic synthesis of phthalazinones has been developed using phthalaldehydic acid, 2-acyl-benzoic acid, and substituted hydrazine as simple substrates. The reaction time was shortened to 20–60 min. Structurally diverse phthalaldehydic acids, 2-acyl-benzoic acids, and hydrazines were transformed into phthalazinones with a nearly 100% yield regardless of the aggregate state and electronic nature of the substituents. The transformation was demonstrated to be amenable for scale-up with multiple liquid and solid materials. In addition, isolation and purification of the crude products can be simply done with only crystallization. The heavy metal pollution was also eliminated from the source.

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