Affiliation:
1. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences Lanzhou University 199 West Donggang Road Lanzhou 730000 China
2. Research Unit of Peptide Science, 2019RU066 Chinese Academy of Medical Sciences 199 West Donggang Road Lanzhou 730000 China
3. Technology & Engineering Institute of Lanzhou University Gongyuan Road Baiyin 730900 China
Abstract
AbstractThe photoredox electron donor–acceptor (EDA) complex‐mediated radical coupling reaction has gained prominence in the field of organic synthesis, finding widespread application in two‐component coupling reactions. However, EDA complex‐promoted multi‐component reactions are not well developed with only a limited number of examples have been reported. Herein, we report a photoinduced and EDA complex‐promoted highly chemoselective three‐component radical arylalkylation of [1.1.1]propellane, which allows the direct functionalization of C(sp3)−H with bicyclo[1.1.1]pentanes (BCP)‐aryl groups under mild conditions. A variety of unnatural α‐amino acids, featuring structurally diversified 1,3‐disubstituted BCP moieties, were synthesized in a single‐step process. Notably, leveraging the high tension release of [1.1.1]propellane, the highly unstable transient aryl radical undergoes rapid conversion into a relatively stable tertiary alkyl transient radical, and consequently, the competing side‐reaction of two‐component coupling was entirely suppressed. The strategic use of this transient radical conversion approach would be useful for the design of diverse EDA complex‐mediated multi‐component reactions. It is noteworthy that the highly chemoselective late‐stage incorporation of the 1,3‐disubstituted BCP pharmacophores into peptides was achieved both in liquid‐phase and solid‐phase reactions. This advancement is anticipated to have significant application potential in the future development of peptide drugs.
Funder
National Natural Science Foundation of China
Cited by
4 articles.
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