Toward Rational Understandings of α-C-H Functionalization: Energetic Studies of Representative Tertiary Amines

Wenzhi Luo; Jin-Dong Yang; Jin-Pei Cheng

doi:10.1016/j.isci.2020.100851

Toward Rational Understandings of α-C-H Functionalization: Energetic Studies of Representative Tertiary Amines

iScience. 2020 Feb 21;23(2):100851. doi: 10.1016/j.isci.2020.100851. Epub 2020 Jan 21.

Authors

Wenzhi Luo¹, Jin-Dong Yang², Jin-Pei Cheng³

Affiliations

¹ Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing 100084, China.
² Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing 100084, China. Electronic address: jdyang@mail.tsinghua.edu.cn.
³ Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing 100084, China; State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China. Electronic address: jinpei_cheng@mail.tsinghua.edu.cn.

Abstract

Functionalization of α-C-H bonds of tertiary amines to build various α-C-X bonds has become a mainstream in synthetic chemistry nowadays. However, due to lack of fundamental knowledge on α-C-H bond strength as an energetic guideline, rational exploration of new synthetic methodologies remains a far-reaching anticipation. Herein, we report a unique hydricity-based approach to establish the first integrated energetic scale covering both the homolytic and heterolytic energies of α-C-H bonds for 45 representative tertiary amines and their radical cations. As showcased from the studies on tetrahydroisoquinolines (THIQs) by virtue of their thermodynamic criteria, the feasibility and mechanisms of THIQ oxidation were deduced, which, indeed, were found to correspond well with experimental observations. This integrated scale provides a good example to relate bond energetics with mechanisms and thermodynamic reactivity of amine α-C-H functionalization and hence, may be referenced for analyzing similar structure-property problems for various substrates.

Keywords: Organic Chemistry; Organic Synthesis; Physical Organic Chemistry.