Catalytic C(sp3)-H Trifluoroethylation of Amino Acids and Carboxylic Acids.

Integrating of the trifluoroethyl (-CH2CF3) group into the organic compounds by activating the distal C(sp3)-H bond is a challenging but crucial task in organic chemistry. This transformation imparts unique physicochemical properties to the compounds, such as enhanced lipophilicity, metabolic stability, and altered electronic characteristics. In this study, we unveil a new palladium-catalyzed method to directly introduce the trifluoroethyl group into amino acid and carboxylic acid derivatives. Remarkably, this method effectively activates the ß-C(sp3)-H bond across various substrates at room temperature. Utilizing mesityl(2,2,2-trifluoroethyl)iodonium triflate as a trifluoroethyl source, our approach selectively targets the distal ß-C(sp3)-H bonds of amino and carboxylic acids, ensuring high chemoselectivity and enabling the straightforward synthesis of a diverse array of important γ-trifluoromethyl amino acid and carboxylic acid derivatives. Furthermore, the practical applicability of this methodology is demonstrated through its scalability for gram-scale synthesis.

Diastereoselective Hydroacylation of Cyclopropenes by Visible-Light Photocatalysis.

An efficient and general strategy for the hydroacylation of cyclopropene is disclosed for synthesizing various 2-acylcyclopropane derivatives under mild reaction conditions. High functional group tolerance of this protocol features a novel route to access a divergent synthesis of acylated cyclopropane in a diastereoselective manner by photoinduced decarboxylation of α-ketoacid followed by acyl radical addition to cyclopropene. Additionally, the regioselective addition of acyl radical at the least substituted olefinic carbon center with trans-selective fashion makes this protocol more appealing toward natural product development.

An organo-photocatalyzed visible-light-driven multi-component approach for carbothioaryl/alkylation of activated alkenes via C(sp3)-H bond functionalization.

A visible-light-driven organophotocatalyzed multi-component approach for carbothiolation of activated alkenes is demonstrated under environmentally benign and redox-neutral conditions, involving direct C(sp3)-H functionalization followed by electrophilic alkyl/arylthiolation. The three-component difunctionalization reaction is a complete transition-metal and peroxide-free process conducted under milder conditions. In this composite reaction, by employing bench-stable reagents, the formation of two new C(sp3)-C(sp3) and C(sp3)-S bonds is achieved for a wide variety of substrates, showcasing the excellent functional group tolerance and chemoselectivity of the methodology. Furthermore, the scalability and utilization of natural sunlight instead of artificial blue LEDs, along with the use of an inexpensive and easy-to-prepare pyrylium salt as an organo-photocatalyst, make this protocol greener and more energy efficient.

Palladium-Catalyzed Direct C(sp2)-H Cyanomethylation of Arylamides using Chloroacetonitrile.

In this study, we devised a palladium-catalyzed efficient and versatile method for C(sp2)-H ortho-cyanomethylation of arylamides with a broad substrate scope and moderate to excellent yields. An inexpensive and commercially available chloroacetonitrile was employed as a cyanomethylating source. This method is also compatible with the air atmosphere. Further, the synthetic feasibility of this technique is established by gram-scale synthesis and functional group transformation of the products.

Visible-Light-Driven Organophotocatalyzed Multicomponent Approach for Tandem C(sp3)-H Activation and Alkylation Followed by Trifluoromethylthiolation.

A visible-light-driven organophotocatalyzed multicomponent approach has been developed for tandem direct C(sp3)-H activation and alkylation followed by trifluoromethylthiolation in a one-pot operation. We report a completely metal-free, tandem, three-component approach for the difunctionalization of activated alkenes via the photoinduced radical pathway. This protocol allows the formation of two new C(sp3)-C(sp3) and C(sp3)-SCF3 bonds using a bench-stable, easy-to-handle trifluoromethylthiolating reagent under mild reaction conditions. The generosity of this reaction is shown with a library of C(sp3)-H donors and alkenes derivatives. The reaction conditions can tolerate a wide variety of functional groups. Gram-scale synthesis using environmentally benign and straightforward conditions highlights the synthetic advancement of the methodology. Further functionalization of the final product is also successfully demonstrated.

Diastereoselective palladium-catalyzed C(sp3)-H cyanomethylation of amino acid and carboxylic acid derivatives.

In this study, we report an efficient protocol for Pd-catalyzed methylene ß-C(sp3)-H cyanomethylation of 8-aminoquinoline-directed α-amino acids using inexpensive chloroacetonitrile. Iodoacetonitrile generated in situ from chloroacetonitrile reacts with methylene C(sp3)-H bonds of α-amino acids with excellent diastereoselectivity, enabling access to a wide range of important γ-cyano-α-amino acids. Our protocol works well with different amino acid and carboxylic acid derivatives with good chemical yields and high functional group tolerance.