A chiral ferrocene-tethered ruthenium diamine catalyst has been developed for asymmetric transfer hydrogenation of ketones, enabling asymmetric reduction of a wide range of ketones including aryl alkyl ketones and cyclic dialkyl ketones with excellent reactivities and enantioselectivities. Efficient dynamic kinetic resolution (DKR) of racemic alpha-substituted cyclic ketones was established, affording a series of cyclic chiral alcohols with two contiguous stereocenters in high yields and excellent enantio- and diastereoselectivity levels. The chiral ATH Ru catalyst was found to offer practicality, with a TON of up to 4000.

Enantioselective synthesis of homopropargyl amines from easily available starting materials is attractive and challenging in organic synthesis field. Herein, we reported a copper(I) hydride (Cu-H)-catalyzed reductive coupling reactions of isatin ketimines or aldimines with a broad range of 1,3-enynes bearing silyl, alkyl, aryl, heteroaryl substituents, affording a variety of homopropargyl amines in up to 98 % yield with up to >95:5 dr and >99:1 er. A single multi-functional catalyst effectively controlled the chemo-, regio-, diastereo- and enantioselectivity. Selective deprotection of the resulting enantio-enriched homopropargyl amines followed by functionalizations furnished a variety of useful building blocks.

A diverse range of Pd(II)-catalyzed enantioselective C-H activation reactions have been developed to construct point, axial, and planar chirality. Despite the importance of chiral biaryl scaffolds in bioactive molecules and chiral ligands, atroposelective functionalization at the meta-position remains a significant challenge. Here, we realized a rare atroposelective remote meta-C-H functionalization with a chiral monoprotected amino acid (MPAA) ligand and a racemic transient norbornene mediator. The reaction starts with enantioselective ortho-C-H activation via kinetic resolution to give a chiral biaryl-palladium intermediate, which subsequently undergoes a Catellani relay to afford chiral meta-functionalized biaryl products (S-factors up to 458). The obtained diverse enantioenriched quinoline-based atropisomers are ubiquitous in natural products, pharmaceuticals, chiral ligands, and functional materials. Moreover, unprecedented enantioselective meta-alkenylation and alkynylation have also been developed using this approach. A wide range of synthetic applications of the chiral 8-aryl quinolines, including the synthesis of novel P,N-ligand and chiral functional materials with CPL activity, have been demonstrated.

The selectivity of protein kinase inhibitors (PKIs) remains a major challenge in drug discovery. In this study, we present an ultradeep phosphoproteomics approach for assessing PKI selectivity and elucidating mechanisms of action using Zanubrutinib as a model. Two complementary phosphoproteomics strategies were employed: phosphopeptides enriched with Zr4+-IMAC in combination with TiO2 beads were analyzed using data-independent acquisition (DIA), while tyrosine phosphopeptides enriched with SH2-Superbinder were analyzed via data-dependent acquisition (DDA). The comprehensive phosphoproteomic analysis identified that 97 and 316 phosphosites were significantly altered upon Zanubrutinib stimulation in the DDA and DIA data sets, respectively. Bioinformatics analysis of these phosphoproteins provided a detailed selectivity profile of Zanubrutinib, offering insights into its mechanism of action at the molecular level. Compared to existing methods, our approach is more comprehensive, has higher throughput, and is more precise-not only for PKI selectivity assessment but also for broader cell signaling research.

Aliphatic aldehydes are important building blocks in organ-ic synthesis due to their high reactivity and versatility. Herein, we reporta simple, mild and efficient method for the hydroformylation of allyl al-cohol esters under cobalt catalysis. This procedure offers good func-tional group tolerance, moderate to good product yields and exclusivechemo- and regioselectivity, making it an attractive method to preparealdehydes with linear selectivity.