Lei Chen

Chiral ethers adjacent to a carbonyl group represent a valuable class of motifs; however, their catalytic asymmetric synthesis from readily available carbonyl compounds remains underexplored. Here, we present a catalytic asymmetric umpolung C–O bond-forming reaction of β-keto esters with alkyl hydroperoxides. This protocol employs in situ activation of alkyl hydroperoxides with trichloroacetonitrile, enabling the enantioselective alkoxy transfer to β-keto esters under catalysis by a chiral bifunctional organocatalyst, thereby allowing access to a broad range of highly functionalized, enantioenriched ethers bearing quaternary stereocenters.

Ketones are ubiquitous functional groups and serve as versatile synthetic handles. However, a long-standing challenge in ketone chemistry is the lack of mild, broadly compatible approaches for converting common aliphatic ketones into ketyl-type radicals, especially those circumventing strongly reductive conditions and/or reagents. This limitation has hindered the development of unconventional ketone transformations, particularly the integration of ketyl-type radical generation with transition-metal catalysis for valuable C-C bond formation at carbonyl carbons. Here we report an efficient, mild protocol that converts aliphatic ketones to ketyl-type radicals via a bifunctional silyl reagent. Leveraging a distinct radical translocation strategy, our approach bypasses strongly reductive conditions and enables its merger with Pd catalysis to unlock redox-neutral ketone-olefin couplings. Diverse alkenylation and allylation products were obtained using readily available olefins instead of organometallic reagents, with broad functional group tolerance. Both inter- and intramolecular variations were developed, and this adaptable ketone-to-ketyl-type radical platform may provide access to other valuable ketone transformations.

An efficient β-trifluoromethylation and perfluoroalkylation of enamide derivatives has been achieved under mild, transition metal-free conditions without requiring oxidants or photocatalysts.

Replacing non-renewable fossil resources with sustainable biomass feedstocks represents one of the central missions of modern chemistry. This shift inevitably places urgent demands on chemical methods for biomass degradation, particularly for the efficient and selective cleavage of unstrained C(sp³)−C(sp³) bonds that constitute the backbone of biomass molecules. Herein, 1,3-propanediol, a low-cost biomass-derived bulk chemical, is established as an efficient, green, and sustainable C₁ source for the mono-N-methylation of primary amines via chelation-free C(sp³)−C(sp³) bond cleavage. This method features high mono-N-methylation selectivity, low catalyst loading, wide substrate scope, and mild conditions. Unlike the traditional C−C bond cleavage strategies to avoid the involvement of hydrogen transfer, this reaction instead leverages a hydrogen transfer-triggered N-hydroxyalkylation/retro-Mannich fragmentation pathway to facilitate the scission of unstrained C(sp³)−C(sp³) bond in primary 1,3-diols. This work is anticipated to stimulate innovation in developing new C−C bond cleavage strategies for biomass degradation.

We developed a novel electrochemical reductive coupling of allylbenzenes and vinylarenes, enabling the modular synthesis of 1,4-diarylbutanes with precise C1–C4 modification under mild conditions.