Development of New Organic Photoredox Catalysis Driven by Visible Light

Abstract

Development of efficient and sustainable synthetic technologies for molecular construction is the central goal in modern organic synthesis. In recent decades, organocatalysis has become one of the viable tools in organic synthesis with notable features including easy manipulation, low cost, and/or less susceptible to air and moisture. Organophotoredox catalysis has merged as a front runner in organocatalysis. My Ph.D. study focuses on the development of novel visible-light mediated organic photoredox catalysis strategies for the construction of structurally diverse molecular architectures in distinct ways. In the first efforts, a metal- and oxidant-free organophotocatalytic method for preparing structurally diverse thioesters from readily accessible, abundant aldehydes, has been realized. Excited by blue light, the simple and cost-effective 9,10-phenanthrenequinone (PQ) promotes hydrogen atom transfer (HAT) to selectively generate acyl radicals from corresponding aldehydes without inducing crossover reactivity of thioesters. In situ formed acyl radicals then react with thiosulfonate S-esters to efficiently produce thioesters. The mild and efficient method exhibits excellent substrate scope and outstanding functional group tolerance. Significantly, it is proved to be useful in a late-stage functionalization of complex molecules. Direct H/D exchange at formyl groups represents the most straightforward approach to C-1 deuterated aldehydes. Along this line, a new photoredox catalytic, visible-light mediated neutral radical approach has been developed via a unique double-HAT process. Selective control of highly reactive acyl radical enables driving the formation of deuterated products when an excess of D2O is employed. The power of H/D exchange process has been demonstrated for both aromatic aldehydes and aliphatic substrates, and more important late-stage deuterium incorporation into complex structures with uniformly high deuteration level (>90%). The direct dearomatization of indoles represents the most straightforward access to indolines. However, the exiting dearomative methods largely restrict to electron-rich indoles or go through an ionic process using strong nucleophiles. Toward this end, an unprecedented organophotocatalytic process by harnessing nucleophilic radicals to react with electron-deficient indoles was developed. The preparative power of this radical-engaged strategy has been demonstrated by direct addition of in situ formed nucleophilic radicals from readily accessible feedstock carboxylic acids, into structurally diverse electrophilic indoles including (thio)ester, amide, ketone, nitrile and thus delivering a series of trans-2,3-disubstituted indolines with uniformly high stereoselectivity (> 20:1 dr). Moreover, this approach has also been successfully applied to other aromatic heterocycles such as pyrroles, benzofurans and benzothiophenes.