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Fluorinated amino acids and related peptides/proteins have been found widespread applications in pharmaceutical and agricultural compounds. However, strategies for introducing a C−F bond into amino acids in an enantioselective manner are still limited and no such asymmetric catalysis strategy has been reported. Herein, we have successfully developed a Pd/Cu/Li ternary system for stereodivergent synthesis of chiral fluorinated amino acids. This method involves a sequential desymmetrization of geminal difluoromethylenes and allylic substitution with amino acid Schiff bases via Pd/Li and Pd/Cu dual activation, respectively. A series of non‐natural amino acids bearing a chiral allylic/benzylic fluorine motif are easily synthesized in high yields with excellent regio‐, diastereo‐, and enantioselectivities (up to >20 : 1 dr and >99 % ee). A density functional theory (DFT) study revealed the F−Cu interaction of the allylic substrate and the Cu catalyst significantly influence the stereoselectivity. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Skipped dienes are of great importance but remain challenging to synthesize because of the presence of a sp3 hybrid carbon between the two alkenes. Herein, we have developed the first nickel‐catalyzed regio‐, (E)‐stereo‐ and linear‐selective ring‐opening/cross‐coupling reaction of vinylaziridines with organoboronic acids under mild conditions to construct various skipped aminodienes. The reaction exhibits wide functional‐group compatibility, and could be adapted for the introduction of skipped aminodiene functionality into bioactive molecules. In addition, the reaction could be carried out on a gram‐scale, delivering the ring‐opening products in high yields and with linear‐selectivity (90% yield, l : b >20 : 1). Furthermore, DFT calculations and mechanistic experiments provided detailed insights into the mechanism. [ABSTRACT FROM AUTHOR]

An iridium‐catalyzed remote site‐switchable hydroarylation of alkenes was reported, delivering the products functionalized at the subterminal methylene and terminal methyl positions on an alkyl chain controlled by two different ligands, respectively, in good yields and with good to excellent site‐selectivities. The catalytic system showed good functional group tolerance and a broad substrate scope, including unactivated and activated alkenes. More importantly, the regioconvergent transformations of mixtures of isomeric alkenes were also successfully realized. The results of the mechanistic studies demonstrate that the reaction undergoes a chain‐walking process to give an [Ar−Ir−H] complex of terminal alkene. The subsequent processes proceed through the modified Chalk–Harrod‐type mechanism via the migratory insertion of terminal alkene into the Ir−C bond followed by C−H reductive elimination to afford the hydrofunctionalization products site‐selectively. [ABSTRACT FROM AUTHOR]

A highly chemoselective earth‐abundant transition metal copper catalyzed asymmetric hydrogenation of C=O bonds of exocyclic α,β‐unsaturated pentanones was realized using H2. The desired products were obtained with up to 99 % yield and 96 % ee (enantiomeric excess) (99 % ee, after recrystallization). The corresponding chiral exocyclic allylic pentanol products can be converted into several bioactive molecules. The hydrogenation mechanism was investigated via deuterium‐labelling experiments and control experiments, which indicate that the keto‐enol isomerization rate of the substrate is faster than that of the hydrogenation and also show that the Cu−H complex can only catalyze chemoselectively the asymmetric reduction of the carbonyl group. Computational results indicate that the multiple attractive dispersion interactions (MADI effect) between the catalyst with bulky substituents and substrate play important roles which stabilize the transition states and reduce the generation of by‐products. [ABSTRACT FROM AUTHOR]

Chemiluminescence (CL) has recently emerged as a novel light source for triggering various photoreactions with appealing features such as the elimination of continuous power supply and complex instrumentation. Here, CL‐induced cationic photopolymerization using ferrocenium salts as unimolecular photoinitiators is reported. The ferrocenium salts, facilely synthesized via ligand exchange reactions, absorb the visible light emitted from CL reactions and generate Lewis acids capable of initiating the cationic polymerization of oxirane and vinyl monomers. The presented method can be applied to create linear polymer chains and cross‐linked luminescent polymer networks, which have significant potential in the fabrication of new polymeric materials and various bioapplications. [ABSTRACT FROM AUTHOR]

Chiral α,β‐unsaturated γ‐lactams bearing simple γ‐ substituents are found in biologically active molecules and natural products, however, their synthesis still remains difficult. Herein, we report an efficient kinetic resolution (KR) of γ‐substituted α,β‐unsaturated γ‐lactams via a Cu‐catalyzed asymmetric boron conjugate addition, which also leads to the efficient synthesis of chiral β‐hydroxy‐γ‐lactams with β,γ‐stereogenic carbon centers. The KR proceeded smoothly with a wide range of γ‐alkyl or aryl substituted substrates including those bearing aromatic heterocycles and different N‐protected substrates in up to 347 of s value. Their highly versatile transformations, synthetic utility in biologically active molecules, and inhibitory activities against cisplatin‐sensitive ovarian cancer cell A2780 have also been demonstrated. Differing from the well‐known mechanism involving Cu−B species in Cu‐catalyzed boron conjugate additions, our mechanistic studies using density functional theory (DFT) calculations and experiments indicate that a Lewis acid CuI‐catalyzed mechanism is the likely pathway in the catalytic reaction. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: TBAJ‐876, developed by TB Alliance, a novel anti‐tuberculosis‐specific drug, has entered Phase II clinical trials. Herein, the first asymmetric synthesis of TBAJ‐876 has been realized using synergistic Li/Li catalysis with excellent yield of 95% and 88 : 12 er (99.6 : 0.4 er, 10 : 1 dr after simple recrystallization). Furthermore, DFT calculations and 7Li‐NMR analysis illustrated the mechanism of the synergistic reaction: a chiral Li‐complex activates the nucleophile to control the stereoselectivity, while the other achiral Li‐complex activates the electrophile to catalyze the carbonyl addition reaction. Additionally, this protocol has been successfully carried out at 5 gram‐scale, showing its industrial potential. [ABSTRACT FROM AUTHOR]

The allylic alcohol structural motif is prevalent in many important molecules and valuable building blocks. The rearrangement reaction is one of the most important transformations, however there are only a few reports for the 1,3‐rearrangement of allylic alcohols. Herein, a 1,3‐rearrangement of allylic alcohols catalyzed by an Ir(III) dihydride complex is described. This reaction could provide the corresponding less accessible allylic alcohols regio‐ and stereoselectively from readily available E/Z mixtures of the substrates. Furthermore, a tandem alkene isomerization followed by 1,3‐rearrangement of homoallylic alcohols was also realized. In addition, this rearrangement reaction could be used to synthesize the natural product Navenone B. Mechanistic investigation indicated that the reaction pathway involved a π‐allyl‐Ir(V) intermediate and that the dihydride in the iridium catalyst acts as a hydrogen switch to modulate the valence of the iridium center. [ABSTRACT FROM AUTHOR]

The stereodivergent synthesis of allene compounds bearing α,β‐adjacent central chiralities has been realized via the Pd/Cu‐catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl‐substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non‐natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo‐ and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommon η3‐butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2−Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT). [ABSTRACT FROM AUTHOR]

The first asymmetric Ni/Cu cocatalyzed benzylation of aldimine esters is reported. A series of benzyl‐substituted α‐quaternary amino acids could be synthesized in high yield and with high levels of enantioselectivity (up to 90 % yield and 99 % ee). The experimental and theoretical calculation results suggested that the strong electrophilicity of the η3‐benzylnickel intermediate is crucial for the high reactivity, enabling the reaction under base‐free conditions. Furthermore, this method has been applied to the synthesis of the cell adhesion inhibitor BIRT‐377 analogues, and the key intermediate of the NK1 receptor antagonist PD154075 and CCK‐B receptor antagonist CI‐988. [ABSTRACT FROM AUTHOR]

Asymmetric desymmetrization has been demonstrated to be a powerful strategy for building stereocenters in asymmetric synthesis. Herein, a Pd/Cu catalyzed asymmetric desymmetrization reaction with a simple geminal dicarboxylate is reported. A wide scope of imino esters bearing an aryl or heteroaromatic group were compatible with this bimetallic catalytic system. The reactions proceeded smoothly, giving the desired products in good yields with high to excellent regio‐, diastereo‐, and enantioselectivity (up to 20 : 1 branched:linear, >20 : 1 dr, >99 % ee). Notably, the reaction favored branched selectivity, which is unusual for the Pd‐catalyzed allylic alkylation reaction. In addition, the standard product could be easily transformed to other valuable molecules such as chiral allylic alcohols, carbamates, and organic boron compounds. Furthermore, DFT calculations were conducted to explain the origin of the branched selectivity. [ABSTRACT FROM AUTHOR]

The development of efficient and straightforward methods for obtaining all optically active isomers of structurally rigid spirocycles from readily available starting materials is of great value in drug discovery and chiral ligand development. However, the stereodivergent synthesis of spirocycles bearing multiple stereocenters remains an unsolved challenge owing to steric hindrance and ring strain. Herein, we report an enantio‐ and diastereodivergent synthesis of rigid spirocycles through dual‐metal‐catalyzed [3+2] annulation of oxy π‐allyl metallic dipoles with less commonly employed nucleophilic dipoles (imino esters). A series of spiro compounds bearing a pyrroline and an olefin were easily synthesized in an enantio‐ and diastereodivergent manner (up to 19:1 dr, >99 % ee), which showed great promise as a new type of N‐olefin ligand. Preliminary mechanistic studies were also carried out to understand the process of this bimetallic catalysis. [ABSTRACT FROM AUTHOR]

3,3‐Disubstituted oxindoles bearing quaternary and tertiary stereogenic centers are privileged structural motifs, which widely exist in pharmaceutical and natural products. Herein, a highly regio‐, enantio‐, and diastereoselective allylic alkylation of 3‐alkyl oxindoles through synergistic iridium and copper catalysis is described, which provides a series of 3,3‐disubstituted oxindole derivatives containing adjacent quaternary and tertiary stereogenic centers in excellent yields, enantiomeric excess, and diastereomeric ratio (for 30 examples, up to 97 % yield, >99 % ee, and >20 : 1 dr). This method provides exclusive branched selectivity, excellent enantio‐ and diastereoselectivities, and good functional compatibility. Control experiments suggested that the chiral copper catalyst is required for achieving high reactivities and diastereoselectivities under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Skipped dienes are of great importance but remain challenging to synthesize because of the presence of a sp3 hybrid carbon between the two alkenes. Herein, we have developed the first nickel‐catalyzed regio‐, (E)‐stereo‐ and linear‐selective ring‐opening/cross‐coupling reaction of vinylaziridines with organoboronic acids under mild conditions to construct various skipped aminodienes. The reaction exhibits wide functional‐group compatibility, and could be adapted for the introduction of skipped aminodiene functionality into bioactive molecules. In addition, the reaction could be carried out on a gram‐scale, delivering the ring‐opening products in high yields and with linear‐selectivity (90% yield, l : b >20 : 1). Furthermore, DFT calculations and mechanistic experiments provided detailed insights into the mechanism. [ABSTRACT FROM AUTHOR]