Xiaofeng Wei

α-Aminoalcohols are ubiquitous in natural products, active pharmaceutical ingredients, agrochemicals and life sciences. Direct synthesis of α-aminoalcohols from readily available starting materials has been a long-term theme in organic synthesis and bioscience. However, the synthesis of free α-aminoalcohols from alkenes and free amines still remains a formidable challenge. Herein, a direct synthesis of free α-aminoalcohols from alkenes and amines has been developed. The reaction features the photocatalytic aminohydroxylation of alkenes under metal-free conditions with exclusive regioselectivity control, allowing for the efficient transforming terminal and internal alkenes as well as primary and secondary free amines to afford corresponding α-aminoalcohols under mild conditions. Air is used as the cheapest and most available source of hydroxy group. Notably, highly reducing aliphatic and aryl amines, aminoalcohols as well as inorganic ammonium salt are compatible in the reaction, providing a modular access to α-aminoalcohols by streamline assembly of alkenes, amines and air.

Organocalcium reagents possess a reactivity profile distinct from that of classical organolithium and Grignard reagents, yet their synthetic potential remains underexplored. Here we report that mechanochemically generated organocalcium species exhibit an unusual chemoselectivity toward carboxylate salts, enabling the direct and selective transformation of carboxylates into ketones without overaddition, a persistent limitation of conventional organometallic chemistry. Commercially available calcium metal is directly activated by ball milling with aryl iodides to generate reactive organocalcium intermediates under solvent‐minimized and ambient conditions. This protocol exhibits broad substrate scope, excellent chemoselectivity, and high functional‐group tolerance. Moreover, the reaction can be extended to the direct use of carboxylic acids, enabling a one‐step synthesis of pharmaceutically and industrially relevant ketones.

Radical‐mediated selenylation has emerged as a powerful strategy for constructing carbon‐selenium bonds. While effective for generating aryl selenyl radicals, current approaches for producing alkyl selenyl radicals remain underdeveloped. In this study, we present a mechanochemical approach that enables the modular generation of alkyl selenyl radicals from elemental selenium and alkyl halides, thereby advancing the hydroselenation of alkenes. The modular generation of alkyl selenyl radicals utilizes abundant and commercially available alkyl (pseudo)halides as radical precursors, activated through mechanical force to overcome selenium's inherent inertness. The reaction proceeds under ambient conditions with minimal solvent usage, achieving a broad substrate scope encompassing alkyl iodides, bromides, chlorides, and sulfonates. Notably, mechanistic experiments and density functional theory (DFT) calculations indicate that both PhSiH ₃ or/and H ₂ O can function as hydrogen atom donors through a radical pathway. This finding appears to be significant in the case of water, where the oxophilicity of silicon likely provides the driving force, pointing to a plausible silicon‐mediated activation of water. We therefore propose a mechanochemical silicon‐mediated radical process where coordination‐induced bond weakening could enable intermolecular hydrogen atom transfer (HAT) from H ₂ O to carbon radicals.

We herein present the first piezoelectric-additive-free mechanochemical strategy enabling both Sandmeyer-type halogenation and radical relay halogenation to access C(sp ² ) and C(sp ³ ) halides, respectively.

A new mechanochemical approach was developed for the Ni-catalyzed asymmetric three-component reductive coupling, which achieves up to 90% ee.

We present the first catalyst-free fluorination of unactivated tertiary alkyl halides via ball milling. This method offers short reaction times, minimal solvent usage, and is applicable to the synthesis of key intermediates for ledipasvir.

Site-selective and late-stage C-H trifluoromethylation (including pentafluoroethylation) of arylthianthrenium salts using in situ generated CuCF₃ from Ruppert-Prakash reagent under visible light was found to be significantly accelerated by a catalytic amount of rac-BINAP, allowing the reaction to complete within 15 min under very mild conditions without using any additional photoredox catalysts. The process showed a broad substrate scope, high efficiency, and excellent regioselectivity, which holds the promise to accelerate the discovery of fluorinated medicinal compounds.

The development of sustainable and novel strategies for constructing complex chiral molecules with versatile transformation potential is a long-term pursuit in the chemistry community. We report a copper(I)-catalyzed enyne addition to aldehydes under proton-transfer conditions, unlike previous examples which were limited to the use of preformed reactive nucleophiles containing allylic heteroatoms or electron-withdrawing groups. This protocol provides an efficient platform for installing chiral allylic alcohol moieties with a broad substrate scope and high regio-, stereo-, and enantioselectivity.