Rhodium-catalyzed regio- and enantioselective allylic arylation of racemic alkyl- and aryl- substituted allylic carbonates with arylboronic acids using commercially available BIBOP ligand is reported. This reaction proceeds at room temperature without base or other additive to deliver allylic arylation products in excellent yields, regio- and enantioselectivity (up to 95% yield, >20:1 b/l, >99% ee). Rh/BIBOP is disclosed as an efficient catalytic system for allylic substitution reaction.

Crispine A is a representative alkaloid bearing pyrrolo[2,1-a]isoquinoline to exhibit various biological activities. In this report, enantiodivergent synthesis of crispine A has been achieved, featuring a stereoselective 1,3-dipolar cycloaddition and an enzymatic kinetic resolution. The sequential process including cleavage of the N-O bond and cyclization proved to be effective and practical toward pyrrolo[2,1-a]isoquinoline in intriguing bioactive alkaloids. The capacity of enzymatic resolution dictated in this work is of great interest to accumulate the tetrahydroisoquinoline (THIQ)-fused pyrrolidine which is commonly embedded in various bioactive compounds.

In this paper, we report a visible light-mediated aza-Norrish-Yang type cyclization upon energy transfer catalysis for the rapid construction of thiazaspiro[3.4]octanes or hexahydropyrrolo[b]isothiazoles from benzyloxy cyclosulfonimides or acetal cyclosulfonimides, along with broad substrate scope. In addition, most of the thiazaspiro[3.4]octane derivatives are obtained with complete diastereoselectivities. However, for ortho-electron-withdrawing group substituted substrates, moderate diastereoselectivities were observed, probably due to the influence of the torquoelectronic effect. This photochemical process is initiated by the formation of a triplet state of cyclic imine, followed by 1,5-hydrogen atom abstraction (1,5-HAA) and cyclization steps. The plausible reaction mechanisms have been validated through a series of experimental procedures, including control experiments, kinetic studies, deuterium labeling experiments, electrochemical analysis, Stern-Volmer analysis, and density functional theory (DFT) calculations. Based on DFT calculations, we have elucidated the origins of the stereoselectivity and chemoselectivity of this protocol.

Herein, we report a catalytic reductive [4+1] sila-cycloaddition between functionalized 1,3-dienes and chemical feedstock di-, tri-, and tetrachlorosilane(s), enabled by a cost-effective pyridine-diimine-nickel complex, providing a practical method to prepare diverse silacyclopent-3-enes in up to 92% yield, including bridged and spiro silacarbocycles. This reaction demonstrates a broad substrate compatibility, including 1,3-dienes with different substitution patterns and a more accessible E/Z isomeric mixture. Notably, trichlorosilanes undergo tandem [4+1] sila-cycloadditions/nucleophilic substitutions, while tetrachlorosilane successfully performs double [4+1] sila-cycloadditions with 2 equiv of 1,3-dienes to directly construct spiro silacarbocycles.

In this report, the reaction mechanism of triphenylphosphite addition to beta-nitrostyrene is theoretically investigated. The M062X method, a subset of density functional theory (DFT), and the def2svp basis set are used to determine the appropriate mechanism. Three plausible mechanistic routes, labeled pathways A, B, and C, are proposed. In pathway A, triphenyl phosphite is added to the beta-position of beta-nitrostyrene. Pathway B involves the addition of the triphenyl phosphite molecule to the oxygen of the nitro group in beta-nitrostyrene. In pathway C, triphenyl phosphite is added to the nitrogen of the beta-nitrostyrene compound. Since the reaction requires the presence of two mmol of triphenyl phosphite to form the desired product, all three routes of the proposed mechanism are designed accordingly. In the gas phase, the overall energy barriers of paths A and B are 19.31 and 43.47 kcal mol(-1), respectively, while no reliable transition state is obtained for path C. For path A in different solvents, the overall energy barriers are 20.75, 20.76, and 20.76 kcal mol(-1), respectively in water, methanol, and dimethylformamide. Therefore, path A is a more favorable path, and there is not a meaningful difference between the results of the gas phase and different solvents.

Herein we describe the first transition-metal-catalyzed asymmetric Cloke-Wilson rearrangement through unprecedented propargylic alkenoxylation reaction with enol as the O-nucleophile. A set of new chiral PPBOX ligands was prepared to guarantee the high enantioselectivity of the transformation. A series of polysubstituted dihydrofuran skeletons bearing an alkyne unit was prepared in good yield and high enantioselectivity under very mild reaction conditions, and various downstream transformations were facilely conducted to access different chiral skeletons.

A transition-metal-free C-H functionalization method has been developed for the synthesis of aryl sulfoximines. This two-step protocol involves the 3,5-dimethyl-4-isoxazolyliodonium salt as an intermediate. The iodonium salt is obtained with high site selectivity from arenes via C-H activation, and is then converted into sulfoximines through a ligand coupling at the hypervalent iodine center with sulfinamides. The process is mild and does not require transition metals, enabling the late-stage incorporation of chiral sulfonimidoyl groups into drug candidates.

Lysine residue represents an attractive site for covalent drug development due to its high abundance (5.6%) and critical functions. However, very few lysines have been characterized to be accessible to covalent ligands and perturb the protein functions, owing to their protonation state and adjacent steric hindrance. Herein, we report a new lysine bioconjugation chemistry, O-cyanobenzaldehyde (CNBA), that enables selective modification of the lysine epsilon-amine to form iso-indolinones under physiological conditions. Activity-based proteome profiling enabled the mapping of 3451 lysine residues and 85 endogenous kinases in live cells, highlighting its potential for modifying hyper-reactive lysines within the proteome or buried catalytic lysines within the kinome. Further protein crystallography and mass spectrometry confirmed that K271_ABL1 and K162_AURKA are covalently targetable sites in kinases. Leveraging a structure-based drug design, we incorporated CNBA into the core structure of Nutlin-3 to irreversibly inhibit the MDM2-p53 interaction by targeting an exposed lysine K94 on the surface of murine double minute 2. Importantly, we have demonstrated the potential application of CNBA as a lysine-recognized bioconjugation agent for developing new antibody-drug conjugates. The results collectively validate CNBA as a new selective and efficient modifying agent with broad applications for both buried and exposed lysine residues in live cells.