The group of Guosheng Liu at the State Key Laboratory of Metal Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences has developed the first palladium-catalyzed remote hydrohalogenation (including bromination and chlorination) of internal olefins, and the introduction of hydroxyl groups in pyridine-oxazoline ligands (Pyox) is the key to regulate the chemistry and regioselectivity of the reaction; the catalytic system is applicable to various substituted intramolecular olefins and terminal olefins, and exhibits very excellent regioselectivity, providing a new approach for the efficient conversion of mixed olefins to straight-chain alkyl halides. The work was published online in the journal Nature Chemistry in the early morning of February 1, 2022 (DOI: 10.1038/s41557-021-00869-x). Li Hong, a postdoctoral fellow in Guosheng Liu's group, and Jin Jianbo, a graduate student, are co-first authors of the paper, with the Shanghai Institute of Organic Chemistry as the first unit.

Straight-chain alkyl halides are widely used fine chemicals in organic synthesis, and are also common fragments in natural products, pharmaceuticals and pesticides as well as materials molecules, which usually require multi-step synthesis with the help of functional group conversion reactions to obtain. In contrast, the classical acid-catalyzed hydrohalogenation of olefins often yields products dominated by martensine addition or even a single martensine product. Therefore, the inverse martensite hydrohalogenation reactions of terminal olefins are extremely challenging. Not to mention, how difficult it is to convert intramolecular olefins and mixed olefins, the most basic raw materials in petrochemicals, into straight-chain alkyl halides.

Guosheng Liu's group at the Shanghai Institute of Organic Chemistry has long been engaged in the bifunctionalization of olefins (Acc. Chem. Res. 2016, 49, 2413) and has focused on exploring the asymmetric bifunctionalization of inactive olefins, developing new reactions such as intramolecular asymmetric amination of olefins based on Pd(IV) chemistry through the modification of Pyox ligands (J. Am. Chem. Soc. 2018, 140, 7415; Angew. Chem., Int. Ed. 2019, 58, 2392; 2020, 59, 2735; 2020, 59, 17239) and the realization of asymmetric double oxidation and oxycarbonylation reactions of simple terminal olefins (Nat. Catal. 2021, 4, 172. Angew. Chem. Int. Ed. 2021, 60, 14881). On this basis, they explored the selective hydrohalogenation reactions of simple olefins and achieved the first remote hydrochlorination and hydrobromination of intramolecular olefins based on hydrogen bonding by introducing hydroxyl groups in pyridoxazoline with NCS as the chloride source and Na-NMBI as the bromine source to obtain the corresponding straight-chain alkyl halides with high selectivity, and the reactions were equally well functional group compatible. Notably, the catalytic system is also applicable to mixed olefin substrates of alkane dehydrogenation to obtain terminal chlorination or bromination products in moderate to good yields singly, providing a new idea and a new way for the high-value conversion of cheap and easily available alkanes.

This work was supported by the National Key R&D Program of the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences, the Shanghai Municipal Science and Technology Commission, and the Shanghai Leading Talents Program.

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