Straightforward construction of functionalized γ-lactams via conjugated-engineered covalent organic framework photocatalysed cascade reactions
Xiangfeng Lin, Jianguo Li, Jiaxian Zheng, Xiaowei Cai, Liwei Wang, Rongjian Sa, Chuanling Si, Dong Jiang, Yunqing Kang, Jie Wang, Yusuke Yamauchi, Zhanhui Yuan
Abstract
Straightforward synthetic approach for direct constructing functionalized γ-lactams is highly valuable given their ubiquity in bioactive molecules yet challenging due to instability of the products and difficulties in controlling diastereoselectivity. We herein report the design and synthesis of a naphthyl-based pyrene-containing covalent organic framework and utilize it as heterogeneous photocatalyst in visible-light catalytic cascade reactions between tryptamine-derived isocyanides and phosphine oxides. A broad range of 3-(2-aminophenyl)-γ-lactams are isolated in good yields under mild conditions and 3-(2-isocyanobenzyl)-indoles are also tolerated, giving (2-aminophenyl)-tetrahydroquinolines in moderate yield. Experimental studies and theoretical calculations reveal that a proton-coupled electron transfer process occurs between the excited covalent organic framework and phosphine oxide, which subsequently triggers a series of cascade reactions involving cyclization, semipinacol rearrangement, and dehydrogenation/hydration processes. Notably, the in situ generated spiroindolenine is identified to be the key intermediate. Illustrated by the efficient synthesis of 3-(2-aminophenyl)-γ-lactams, this work sets a precedent for the development of heterogeneous photocatalytic strategies for constructing complex bioactive molecules.