1. Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters
Peng-Fei Wang, Jiao Yu, Kai-Xin Guo, Sheng-Peng Jiang, Ji-Jun Chen, Qiang-Shuai Gu, Ji-Ren Liu, Xin Hong, Zhong-Liang Li, Xin-Yuan Liu J Am Chem Soc. 2022 Apr 13;144(14):6442-6452. doi: 10.1021/jacs.2c00957. Epub 2022 Apr 1.
The enantioconvergent radical C(sp3)-C(sp2) cross-coupling of alkyl halides with alkenylboronate esters is an appealing tool in the assembly of synthetically valuable enantioenriched alkenes owing to the ready availability, low toxicity, and air/moisture stability of alkenylboronate esters. Here, we report a copper/chiral N,N,N-ligand catalytic system for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters (>80 examples) with good functional group tolerance. The key to the success is the rational design of hemilabile N,N,N-ligands by mounting steric hindrance at the ortho position of one coordinating quinoline ring. Thus, the newly designed ligand could not only promote the radical cross-coupling process in the tridentate form but also deliver enantiocontrol over highly reactive alkyl radicals in the bidentate form. Facile follow-up transformations highlight its potential utility in the synthesis of various enantioenriched building blocks as well as in the late-stage functionalization for drug discovery.
2. Electrochemical Benzylic C(sp3)-H Acyloxylation
Alexander P Atkins, Albert C Rowett, David M Heard, Joseph A Tate, Alastair J J Lennox Org Lett. 2022 Jul 22;24(28):5105-5108. doi: 10.1021/acs.orglett.2c01930. Epub 2022 Jul 13.
The development of sustainable C(sp3)-H functionalization methods is of great interest to the pharmaceutical and agrochemical industries. Anodic oxidation is an efficient means of producing benzylic cations that can undergo subsequent in situ nucleophilic attack to afford functionalized benzylic products. Herein, we demonstrate the suitability of carboxylic acids as nucleophiles to yield benzylic esters. This method employs a series of secondary benzylic substrates and functionalized carboxylic acids and is demonstrated on a gram scale in flow.
3. N-carboxy-L-aspartic anhydride benzyl ester
Hitoshi Kanazawa, Jun Magoshi Acta Crystallogr C. 2003 Mar;59(Pt 3):o159-61. doi: 10.1107/s0108270103002567. Epub 2003 Feb 28.
The structure of the title compound, benzyl (1,2,3,4-tetrahydro-2,5-dioxo-1,3-oxazol-4-yl)acetate, C(12)H(11)NO(5), has been determined in an attempt to explain the polymerization observed in the solid state. The molecules are linked by intermolecular hydrogen bonds between the imino group of the five-membered ring and an adjacent carbonyl O atom, along the c axis. Intramolecular hydrogen bonds are also formed, between the imino group and the carbonyl O atom of the ester group. The five-membered rings are arranged in a layer, sandwiched by layers incorporating the benzyl groups. This structure is thought to be preferable for the polymerization of the compound in the solid state, because the five-membered rings can react with each other in the layer.
