Asymmetric 2,3-Addition of Sulfinylamines with Arylboronic Acids Enabled by Nickel Catalysis.

Sulfinamides have been widely used in organic synthesis, with research on their preparation spanning more than a century. Despite advancements in catalytic methodologies, creating sulfur stereocenters within these molecules remains a significant challenge. In this study, we present an effective and versatile method for synthesizing a diverse range of S-chirogenic sulfinamides through catalytic asymmetric aryl addition to sulfinylamines. By utilizing a nickel complex as a catalyst, this process exhibits impressive enantioselectivity and can incorporate various arylboronic acids at the sulfur position. The resulting synthetic sulfinamides are stable and highly adaptable, allowing for their conversion to a variety of sulfur-containing compounds. Our study also incorporates detailed experimental and computational studies to elucidate the reaction mechanism and factors influencing enantioselectivity.

Nickel-Catalyzed Asymmetric Propargyl-Aryl Cross-Electrophile Coupling.

Performing asymmetric cross-coupling reactions between propargylic electrophiles and aryl nucleophiles is a well-established method to build enantioenriched benzylic alkynes. Here, a catalytic enantioselective propargyl-aryl cross-coupling between two electrophiles was achieved for the first time in a stereoconvergent manner. Propargylic chlorides were treated with aryl iodides as well as heteroaryl iodides in the presence of a chiral nickel complex, and manganese metal was used as a stoichiometric reductant, allowing for the construction of a propargyl C-aryl bond under mild conditions. An alternative dual nickel/photoredox catalytic protocol was also developed for this cross-electrophile coupling in the absence of a metal reductant. The potential utility of this conversion is demonstrated in the facile construction of stereoenriched bioactive molecule derivatives and medicinal compounds based on the diversity of acetylenic chemistry. Detailed experimental studies have revealed the key mechanistic features of this transformation.

Stereospecific nickel-catalyzed [4+2] heteroannulation of alkynes with aminophosphanes.

Enantioenriched phosphorus compounds play crucial roles in many fields ranging from catalyst to materials science to drug development. Despite advances in the construction of phosphacycles, incorporation of a P-chirogenic center into heterocycles remains challenging. Here, we report an effective method for the preparation of phosphacycles through nickel-catalyzed [4+2] heteroannulation of internal alkynes with aminophosphanes derived from o-haloanilines. Notably, chiral 2-λ5-phosphaquinolines can be prepared from P-stereogenic substrates via NH/PH tautomeric equilibrium without loss of stereochemical integrity. The strategy is found to exhibit a broad scope in terms of both reaction components, enabling modular construction of libraries of 2-λ5-phosphaquinolines with different steric and electronic properties for fine-tuning photophysical properties, where some of these compounds showed distinct fluorescence with high quantum yields. A series of mechanistic studies further shed light on the pathway of the heteroannulation and reasons for stereospecificity.

Orthogonal excitations of lanthanide nanoparticle up/down conversion emissions via switching NIR lights for in-vivo theranostics.

With multiple emissions ranging from NIR-IIb to visible lights, near-infrared light-excited lanthanide nanoparticle (LnNP) is an ideal in-vivo theranostic platform to achieve imaging guided phototherapy. However, current reported LnNPs typically demonstrate simultaneous up and downconversion emissions with fixed single excitation light, which impairs therapeutic efficiency and generates side effect during navigation. Here we develop a lanthanide-based conversion switching nanoparticle (CSNP) with independent activation of 1550 nm NIR-IIb downconversion emission under 808 nm excitation and 345/450 nm upconversion emission under 980 nm excitation. CSNP is modified with Cy-GSH to quench NIR-IIb emission and photosensitizer hypocrellin A. In vivo delivery of CSNP is traced via 808 nm irradiation, and Cy-GSH changes structure in response to glutathione to activate NIR-IIb imaging. This indicates the tumor position and timing to switch for 980 nm irradiation to activate hypocrellin A for photodynamic therapy. Orthogonal activation of CSNP up/down conversion emissions demonstrates high tumor-to-normal tissue ratio in vivo and good therapeutic result, would have promising potential as a theranostics platform.

PIII -Directed Late-Stage Ligation and Macrocyclization of Peptides with Olefins by Rhodium Catalysis.

Transition metal-catalyzed C-H activation is a step-economical strategy for peptide functionalization. Herein, we report the method of late-stage peptide ligation and macrocyclization through rhodium-catalyzed alkylation of tryptophan residues at the C7 position. This method utilizes a N-Pt Bu2 directing group and tolerates various peptide and alkene substrates. Utilizing internal olefins, this study represents the first example of site-selective peptide C-H alkylation through deconjugative isomerization. Furthermore, our method provides access to peptide macrocycles with unique Trp(C7)-alkyl crosslinks and potent cytotoxicity towards cancer cells.

Nickel-Catalyzed Intermolecular Asymmetric Addition of Aryl Iodides across Aldehydes.

Enantioenriched alcohols comprise much of the framework of organic molecules. Here, we first report that chiral nickel complexes can catalyze the intermolecular enantioselective addition of aryl iodides across aldehydes to provide diverse optically active secondary alcohols using zinc metal as the reducing agent. This method shows a broad substrate scope under mild reaction conditions and precludes the traditional strategy through the pre-generation of organometallic reagents. Mechanistic studies indicate that an in situ formed arylnickel, instead of an arylzinc, adds efficiently to aldehydes, forming a new C-C bond and a chiral nickel alkoxide that may be turned over by zinc powder.

Nickel-Catalyzed Stereo- and Enantioselective Cross-Coupling of gem-Difluoroalkenes with Carbon Electrophiles by C-F Bond Activation.

Stereo- and enantioselective cross-electrophile coupling involving C-F bond activation is reported. Treatment of gem-difluoroalkenes with racemic benzyl electrophiles in the presence of a chiral nickel complex using B2 pin2 as a stoichiometric reductant allows the construction of a C(sp2 )-C(sp3 ) bond under mild conditions, affording a broad range of monofluoroalkenes bearing stereogenic allylic centers. Initial mechanistic studies indicate that a radical chain pathway may be operating, wherein the ester group in the gem-difluoroalkene promotes C-F bond activation through oxidative addition to a Ni species.

SOMOphilic Alkynylation of Unreactive Alkenes Enabled by Iron-Catalyzed Hydrogen Atom Transfer.

We report an efficient and practical iron-catalyzed hydrogen atom transfer protocol for assembling acetylenic motifs into functional alkenes. Diversities of internal alkynes could be obtained from readily available alkenes and acetylenic sulfones with excellent Markovnikov selectivity. An iron hydride hydrogen atom transfer catalytic cycle was described to clarify the mechanism of this reaction.

Bioinspired design of a robust d 3-methylating agent.

Methods to incorporate deuterium atoms into organic molecules are valuable for the pharmaceutical industry. The introduction of deuterium atoms by a synthetic method enables the direct tracing of the drug molecule without substantially altering its structure or function. The methyl group is one of the most commonly occurring carbon fragments in biologically active molecules. Here, a biomimetic design reagent, 5-(methyl-d 3)-5H-dibenzo[b,d]thiophen-5-ium trifluoromethane sulfonate (DMTT), as an analog of S-adenosylmethionine (SAM), has been developed for the selective d 3-methylation of complex molecules bearing several possible reactive sites with excellent selectivity and high-level deuterium incorporation. A series of d 3-methylated organic molecules and deuterated pharmaceuticals were synthesized under the mild system with excellent functional group compatibility.

Nickel-catalysed retro-hydroamidocarbonylation of aliphatic amides to olefins.

Amide and olefins are important synthetic intermediates with complementary reactivity which play a key role in the construction of natural products, pharmaceuticals and manmade materials. Converting the normally highly stable aliphatic amides into olefins directly is a challenging task. Here we show that a Ni/NHC-catalytic system has been established for decarbonylative elimination of aliphatic amides to generate various olefins via C-N and C-C bond cleavage. This study not only overcomes the acyl C-N bond activation in aliphatic amides, but also encompasses distinct chemical advances on a new type of elimination reaction called retro-hydroamidocarbonylation. This transformation shows good functional group compatibility and can serve as a powerful synthetic tool for late-stage olefination of amide groups in complex compounds.

Nickel-Catalyzed Decarbonylative Borylation of Amides: Evidence for Acyl C-N Bond Activation.

A nickel/N-heterocyclic carbene catalytic system has been established for decarbonylative borylation of amides with B2 nep2 by C-N bond activation. This transformation shows good functional-group compatibility and can serve as a powerful synthetic tool for late-stage borylation of amide groups in complex compounds. More importantly, as a key intermediate, the structure of an acyl nickel complex was first confirmed by X-ray analysis. Furthermore, the decarbonylative process was also observed. These findings confirm the key mechanistic features of the acyl C-N bond activation process.

Nickel-Catalyzed Borylation of Aryl- and Benzyltrimethylammonium Salts via C-N Bond Cleavage.

By developing a mild Ni-catalyzed system, a method for direct borylation of sp(2) and sp(3) C-N bonds has been established. The key to this hightly efficient C-N bond borylative cleavage depends on the appropriate choice of the nickel catalyst Ni(COD)2, ICy·HCl as a ligand, and the use of 2-ethoxyethanol as the cosolvent. This transformation shows good functional group compatibility and can serve as a powerful synthetic tool for gram-scale synthesis and late-stage C-N borylation of complex compounds.