Jian-Heng Ye

Lactamization of sp2 C−H Bonds with CO2: Transition‐Metal‐Free and Redox‐Neutral

The first direct use of carbon dioxide in the lactamization of alkenyl and heteroaryl C-H bonds to synthesize important 2-quinolinones and polyheterocycles in moderate to excellent yields is reported. Carbon dioxide, a nontoxic, inexpensive, and readily available greenhouse gas, acts as an ideal carbonyl source. Importantly, this transition-metal-free and redox-neutral process is eco-friendly and desirable for the pharmaceutical industry. Moreover, these reactions feature a broad substrate scope, good functional group tolerance, facile scalability, and easy product derivatization.

Selective Oxytrifluoromethylation of Allylamines with CO2

Reported is the first oxy-trifluoromethylation of allylamines with carbon dioxide (CO2 ) using copper catalysis, thus leading to important CF3 -containing 2-oxazolidones. It is also the first time CO2 , a nontoxic and easily available greenhouse gas, has been used to tune the difunctionalization of alkenes from amino- to oxy-trifluoromethylation. Of particular note, this multicomponent reaction is highly chemo-, regio-, and diastereoselective under redox-neutral and mild reaction conditions. Moreover, these reactions feature good functional-group tolerance, broad substrate scope, easy scalability and facile product diversification. The important products could also be formed with either spirocycles or two adjacent tetrasubstituted carbon centers.

Photochemical Carboxylation of Activated C(sp3)−H Bonds with CO2

From ugly duckling to beautiful C1: Although CO2 may represent an ideal C1 source, it is challenging to use it as a raw material and direct carboxylation with CO2 has mainly been confined to highly reactive species. However, recent significant breakthroughs have been made in photochemical carboxylation of challenging, un-acidic, C(sp3 )-H bonds, including benzylic, allylic and amine C-H bonds.

Highly Regio- and Enantioselective Copper-Catalyzed Reductive Hydroxymethylation of Styrenes and 1,3-Dienes with CO2

Herein, we report a highly regio- and enantioselective copper-catalyzed reductive hydroxymethylation of styrenes and 1,3-dienes with 1 atm of CO2. Diverse important chiral homobenzylic alcohols were readily prepared from styrenes. Moreover, a variety of 1,3-dienes also were converted to chiral homoallylic alcohols with high yields and excellent regio-, enantio-, and Z/E-selectivities. The utility of this transformation was demonstrated by a broad range of styrenes and 1,3-dienes, facile product modification, and synthesis of bioactive compounds (R)-(-)-curcumene and (S)-(+)-ibuprofen. Mechanistic studies demonstrated the carboxylation of phenylethylcopper complexes with CO2 as one key step.

Transition-Metal-Free Lactonization of sp2 C–H Bonds with CO2

The transition-metal-free lactonization of heteroaryl and alkenyl C-H bonds with carbon dioxide is reported to synthesize important coumarin derivatives in moderate to excellent yields. These redox-neutral reactions feature a broad substrate scope, good functional group tolerance, facile scalability, and easy product derivatization.

Visible-Light-Driven Iron-Promoted Thiocarboxylation of Styrenes and Acrylates with CO2

The first thiocarboxylation of styrenes and acrylates with CO2 was realized by using visible light as a driving force and catalytic iron salts as promoters. A variety of important β-thioacids were obtained in high yields. This multicomponent reaction proceeds in an atom- and redox-economical manner with broad substrate scope under mild reaction conditions. Notably, high regio-, chemo-, and diasteroselectivity are observed. Mechanistic studies indicate that a radical pathway can account for the unusual regioselectivity.

Oxy-Difluoroalkylation of Allylamines with CO2 via Visible-Light Photoredox Catalysis

A selective oxy-difluoroalkylation of allylamines with carbon dioxide (CO2) via visible-light photoredox catalysis is reported. These multicomponent reactions are efficient and environmentally friendly to generate a series of important 2-oxazolidinones with functionalized difluoroalkyl groups. The good functional group tolerance, broad substrate scope, easy scalability, mild reaction conditions, and facile functionalization of products provide great potential for application in organic synthesis and pharmaceutical chemistry.

Visible‐Light‐Driven Pd‐Catalyzed Radical Alkylation of C─H Bonds with General Unactivated Alkyl Bromides

Reported herein is a novel visible-light photoredox system with Pd(PPh3 )4 as the sole catalyst for the realization of the first direct cross-coupling of C(sp3 )-H bonds in N-aryl tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra- and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp3 )-C(sp3 ) and C(sp2 )-C(sp3 ) bonds in moderate to excellent yields. These redox-neutral reactions feature broad substrate scope (>60 examples), good functional-group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible-light photocatalyst and radicals are involved in the process.

The mechanism of copper-catalyzed oxytrifluoromethylation of allylamines with CO2: a computational study

The trifluoromethyl group (CF3) is a very important functional group. The mechanism of transition metal catalyzed trifluoromethylation has received considerable attention in recent years. In this work, the detailed mechanism of the copper-catalyzed oxytrifluoromethylation of allylamines with CO2 was investigated by density functional theory (DFT) calculations. Differing from the previous Cu(I)–Cu(III) catalytic cycle, the results show that the reaction proceeds through a Cu(I)–Cu(II) catalytic cycle. Deprotonation of allylamines initially occurs with the assistance of a copper catalyst followed by CO2 insertion. In the presence of Togni reagent II, the copper(I) carboxylate species can then be oxidized to the copper(II) dicarboxylate intermediate along with the formation of a free trifluoromethyl radical, which then attacks the alkene moiety to generate the electrophilic addition diradical adduct. The spiro ring is constructed by a carboxylate-delivered radical–radical cross-coupling procedure. In addition, the calculated global electrophilicity shows that the copper(III) intermediate cannot be generated from the combination of the electron deficient copper center and the electrophilic trifluoromethyl radical. Frontier molecular orbital analysis indicates that the Togni reagent II is activated by neutral Cu(I) rather than the cationic Cu(I) species. The origin of the diastereoselectivity can be mainly attributed to the repulsion between the trifluoromethyl group and the carbonyl moiety.

Oxy-Alkylation of Allylamines with Unactivated Alkyl Bromides and CO2 via Visible-Light-Driven Palladium Catalysis

A selective oxy-alkylation of allylamines with unactivated alkyl bromides and CO2 via visible-light-driven palladium catalysis is reported. The commercially available Pd(PPh3)4 is used as the sole catalyst in this three-component reaction. A variety of tertiary, secondary, and primary alkyl bromides undergo reactions to generate important 2-oxazolidinones in high yields and selectivity. The mild reaction conditions, easy scalability, and facile derivatization of products provide great potential for application in organic synthesis and pharmaceutical chemistry.