Iron-catalyzed C-H activation reactions via organometallic Fe-C intermediates have been extensively studied during the past two decades. One issue remains to be clarified is whether iron(III) salts containing weakly coordinating anions could directly activate C(sp2)-H or C(sp3)-H bonds without the assistance of a directing group. Herein, we report our finding that iron(III) salts containing weakly coordinating anions can indeed be effective catalyst for the direct activation of C(sp2)-H and C(sp3)-H bonds under weakly coordinating environment. This mechanism could be extended to other types of first-row transition metal complexes such as Co(II), Ni(II), and Cu(II). Thus, an iron(III) catalyzed H/D exchange reaction for aromatic C(sp2)-H bonds and the corresponding beta-C(sp3)-H bonds of the alkyl substituents is developed, unlocking an easy access to the valuable deuterated aromatic products from feedstock chemicals.

Enantioselective synthesis of chiral compounds is of high interest due to their importance in organic chemistry, medicinal chemistry, life science, and materials science. Catalytic construction of chiral centers via the enantioselective carbon-carbon coupling is one of the most efficient approaches. Chiral 1,5-alkadienes are prevalent in natural and bioactive compounds. Thus, allyl-allyl coupling towards to the synthesis of chiral 1,5-alkadienes is of high interest. However, in addition to the issue of enantioselectivity, the extra challenge is the issue of regio-selectivity referring to the branched and linear products caused by the steric and electronic effect of 1,3-terminals. Herein, such challenge is addressed by a synergistic copper/palladium catalysis strategy: A three-component allylboration reaction of allenes with bis(pinacolato)diboron and allylic phosphates is developed to afford a series of optically active 1,5-alkadienes with either tertiary or quaternary carbon stereocenters. Their synthetic potentials are demonstrated, including the synthesis of (-)-protrifenbute and its derivatives.

Cyclization of bicyclo[1.1.0]butanes (BCBs) is an effective way to construct saturated polycyclic 3D structures. Herein we report a visible-light-induced intramolecular dearomative reaction to forge bicyclo[4.1.1] frameworks through (1,3)-cyclization of BCBs. Moreover, the unprecedented (1,2,3)-cyclization of BCBs through 1,4-hydrogen atom transfer (HAT) process was also realized along with the further transformations. The mechanistic studies revealed that the reaction was initially carried out by an energy transfer (EnT) process and the key open-shell singlet biradical intermediate may undergo [4 pi + 2 sigma] cycloaddition or 1,4-HAT process leading to the formation of two products and we found that the selectivity of product is related to the substituents at the BCBs bridgehead position. Our findings are supported by control experiments, deuterium labeling and kinetic studies, cyclic voltammetry, Stern-Volmer experiments, as well as density functional theory (DFT) calculations.

Chiral allenyl phosphine oxides hold significant application value in organic synthesis, serving as efficient catalysts, ligands, and versatile synthons. However, the development of transition metal-catalyzed asymmetric synthesis for these compounds remains unexplored, primarily due to the facile tautomerization of phosphine oxides into trivalent R1R2P-OH species, which may severely deactivate transition metal catalysts through strong coordination interactions. Herein, a ligand relay strategy has been applied to address this challenge in the Pd-catalyzed enantioselective coupling reactions of propargylic benzoates and secondary phosphine oxides (SPOs) to afford chiral trisubstituted allenyl phosphine oxides with high ee. The ligand relay protocol involves the initial coordination of a palladium catalyst with readily available triphenylphosphine, followed by dynamic ligand exchange with the stretchable chiral ligand DACH-ZYC-Phos-C1 (L26), while PPh3 does not work as a nonchiral ligand for palladium catalysts in this transformation. Chiral trivalent organophosphines with high ee have been obtained upon the reduction of allenyl phosphine oxides. Mechanistic studies revealed the nature of the kinetic resolution. DFT calculations provide a mechanistic rationale for the observed high enantioselectivity and superior catalytic efficiency, which is governed by the ligand L26 through steric repulsions that selectively destabilize the disfavored oxidative addition transition states.

In the past decade, visible-light-mediated photocatalysis has emerged as an applicable strategy for the generation of diverse radical species via single electron transfer (SET) and energy transfer (EnT) processes. Within this context, visible-light-mediated hydrogen atom transfer (HAT) has attracted major interest due to its mild and environmentally benign conditions applied in the selective activation of C-H bonds. Strategies employing C- and heteroatom-centered radical species to selectively activate C-H bonds have become versatile tools due to their mildness and good functional group compatibility for synthesizing value-added products. In this regard, a review on C-centered radical-promoted HAT processes was reported by Gevorgyan's group (Chem. Sci. 2020, 11, 12974, DOI: 10.1039/d0sc04881j), and a review on visible-light-promoted remote C-H functionalization via 1,5-HAT was recently reported by Zhu's group (Chem. Soc. Rev. 2021, DOI: 10.1039/d0cs00774a). Compared to N- and O-centered radical-promoted HAT processes, C(sp(3))-centered radical-promoted HAT is more challenging and less explored due to the small differences in C-H bond dissociation energies. Additionally, in the realm of C-centered radical-promoted HAT, the generation of C-centered radicals has mostly involved SET processes, while the EnT-mediated C-centered radical-promoted HAT process has been less discussed because of the considerable scarcity of related reports. As a result of the rapid advancement of EnT catalysis in synthetic chemistry, C-C-centered biradical species can be readily generated from C=C double bonds via the EnT process using a photocatalyst under visible-light irradiation. An array of transformations (such as cycloaddition and isomerization) involving these C-C-centered biradical species have been reported. Our group recognized these C-C-centered biradicals as practical initiators of the HAT process in C-H functionalization reactions and devoted considerable effort to this field. Initially, we used a triplet excited allene moiety to realize remote sp(3) C-H bond activation successfully. Later, a visible-light-induced triplet biradical HAT reaction of diarylethylenes was disclosed by our group. To further enhance its synthetic applicability, we applied simple styrene derivatives to realize such a novel EnT-mediated HAT process. Detailed control experiments combined with comprehensive density functional theory calculations elucidated the reaction mechanisms of these biradical-mediated HAT reactions along with the subsequent transformations of the obtained products. In addition to the advancements achieved in our group, Bach, Petersen, and others also reported such EnT-mediated HAT processes utilizing aryl acrylamide or aryl acrylate derivatives. Given the rapid progress over the past 5 years and the lack of focused discussion in this area, it is necessary to highlight these reports as a complement to the area of visible-light-mediated HAT via carbon-to-carbon processes. We anticipate that this Account will offer worthwhile insights and serve as guidance for future related research.

Photoinduced electron transfer is fundamental to both biological and synthetic processes; however, modulating back electron transfer (BET) remains a formidable challenge in achieving more efficient photocatalytic transformations. In this work, we present a strategy to regulate electron transfer dynamics via ligand-to-metal charge transfer (LMCT) catalysis, wherein the rapid beta-scission of alkoxy radicals is harnessed to suppress BET, thereby facilitating the efficient transfer of reducing equivalents to drive transition metal-mediated reductive cross-coupling reactions. By strategically utilizing a diverse array of alcohol reductants, such as methanol and pinacol, we employ a cerium benzoate catalyst to enable reductive processes not through modulation of redox potentials, but by promoting synchronized electron transfer. Detailed mechanistic investigations reveal that the photoinduced electron relay process, governed by LMCT-BET, plays a pivotal role in effectively delivering reducing equivalents to catalytic sites, underscoring its significance in optimizing catalytic efficiency.

Radical polymers, containing stable nitroxyl radical, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), within their repeating units, are considered as bipolar cathode materials capable of undergoing both oxidation and reduction in the redox process. However, in most cases, TEMPOcontaining radical polymers are exclusively employed as p-type cathode materials, initially oxidized to a positively charged state, with only one electron being stored or released in the redox process of TEMPO units. Here, a kind of composite material, poly(2,2,6,6-tetramethylpiperidin-1-oxyl-4-yl methacrylate) (PTMA) grafted to reduced graphene oxide, rGO-g-PTMA, is applied as cathode material for zinc-organic battery. Its high specific capacity (>220 mAh g(-1)) and two well-resolved voltage plateaus confirmed the participation of TEMPO reduction in energy storage, as well as the bipolar energy storage capability of PTMA. Its electrochemical reaction mechanism and energy storage performance are also investigated in detail. This first full and distinct utilization of its p- and n-type redox reaction of PTMA opens a new avenue for nitroxyl radicals as high-performance cathode materials for zinc-organic batteries.

Development of catalytic enantioselective transformations through divergent pathways from a single set of starting materials provides one of the most straightforward and efficient strategies for rapid establishment of a library of molecules in chemical synthesis and drug discovery. Catalytic reactions that generate enantioenriched cyclobutenes and cyclobutanes which are not only important units in medicinal chemistry, natural products and material science, but also useful intermediates in organic synthesis are of importance in the field of catalysis. Here we report a cobalt-catalyzed protocol for pathway-divergent enantioselective coupling of alkynes and cyclobutenes. Such processes that begin with oxidative cyclization followed by protonation or reductive elimination accurately controlled by ligands produce densely functionalized cyclobutanes and cyclobutenes in up to 95% yield with >98:2 regio- and diastereoselectivity and >99.5:0.5 enantiomeric ratio. Mechanistic studies and DFT calculations reveal that the reaction pathways are manipulated precisely by ligands and elucidate the origin of stereoselectivity.

The catalytic asymmetric dearomatization of naphthalenes is a pivotal strategy for generating enantioenriched three-dimensional aliphatic polycycles from flat aromatic precursors. However, achieving such transformations involving electronically unbiased naphthalenes remains a long-standing challenge. Here, we describe a silver-mediated enantioselective aza-electrophilic dearomatization approach that couples readily accessible vinylnaphthalenes in conjunction with azodicarboxylates to afford chiral polyheterocycles via formal [4 + 2] cycloaddition reactions, yielding up to 99% yield and 99 : 1 e.r. Central to the method is the formation of an aziridinium intermediate that facilitates the subsequent dearomatization of naphthalenes. A 100 mmol-scale reaction and the divergent transformation of the products into enantioenriched aliphatic polycycles highlight their synthetic utility. Mechanistic experiments and DFT calculations offer insights into the reaction mechanism and the origin of the observed enantiocontrol outcome.

Taurine is a conditionally essential nutrient and one of the most abundant amino acids in humans, with diverse physiological functions. The cellular uptake of taurine is primarily mediated by the taurine transporter (TauT), and its dysfunction leads to retinal regeneration, cardiomyopathy, neurological and aging-associated disorders. Here we determine structures of TauT in two states: the apo inward-facing open state and the occluded state bound with substrate taurine or gamma-aminobutyric acid (GABA). In addition to monomer, the structures also reveal a TauT dimer, where two cholesterol molecules act as molecular glue, and close contacts of two TM5 from each protomer mediate the dimer interface. In combination with functional characterizations, our results elucidate the detailed mechanisms of substrate recognition, specificity and transport by TauT, providing a structural framework for understanding TauT function and exploring potential therapeutic strategies for taurine-deficiency-related disorders.

The self-assembly of biomolecules through noncovalent interactions is critical in both physiological and pathological processes, as exemplified by the assembly of amyloid beta peptide (A beta) into oligomers or fibrils in Alzheimer's disease (AD). Developing molecules that can modulate this assembly process holds significant mechanistic and therapeutic potential. In this study, we identified glycopeptides as a class of protein aggregation modulators, showing that beta-N-acetylgalactosamine (beta-GalNAc)-modified A beta 9-21 promotes A beta 42 fibrillation while reducing its toxic oligomers. Using biochemical assays, cryo-EM, and molecular dynamics simulations, we demonstrated that beta-GalNAc-modified A beta 9-21 coassembles with A beta 42, forming unique fibril structures stabilized by both hydrophobic interactions and an organized hydrogen bond network facilitated by the glycopeptide. Importantly, beta-GalNAc-modified A beta 9-21 can alleviate the neurotoxicity of A beta 42 in neuronal cells and an AD male mouse model. These findings underscore the potential of glycopeptides in regulating amyloid aggregation and provide structural insights for designing molecules targeting amyloid-related pathologies.