Lignin-derived guaiacols as platform chemicals for the modular synthesis of 1,2,3,4-tetrahydroquinolines and benzomorpholines

Abstract

Reductive catalytic fractionation (RCF) has emerged as a centrally important method in modern biorefining, delivering well-defined aromatic platform chemicals from lignin with high selectivity. To establish attractive future biorefinery schemes, urgent attention needs to be devoted to the development of sustainable catalytic methods for the downstream conversion of these aromatic platform chemicals. In this regard, the efficient production of structurally complex, biologically active amines with high atom and step economy represents an attractive goal. Herein, we describe the development of novel catalytic pathways for converting prominent lignin-derived guaiacols that originated during RCF processing into different series of six-membered N-heterocycles, applying hydrogen borrowing amination and C–N cross coupling as key catalytic steps. Specifically, 4-propanol guaiacol (1G) was converted into 1,2,3,4-tetrahydroquinolines 1Gd_n, whereas the formation of benzomorpholines 2–3Gd_n from 4-propyl guaiacol (2G) and 4-ethyl guaiacol (3G) was achieved. The biological activity of the developed compound libraries was evaluated in terms of anticancer activity using human HepG2 cells, which displayed promising activity in several examples.