Direct C?-heteroarylation of structurally diverse ethers via a mild N-hydroxysuccinimide mediated cross-dehydrogenative coupling reaction.

ABSTRACT: An important challenge in the C?-heteroarylation of ethers is the requirement of a large excess amount of ethers (that are used as solvents in many cases) to achieve effective transformations. This drawback has significantly restricted the C?-heteroarylation of ethers to the use of simple and easily accessible ether substrates. To overcome this limitation, a new, efficient, N-hydroxysuccinimide (NHS) mediated, mild and metal-free CDC strategy for the direct C?-heteroarylation of diverse ethers has been developed. Different to our previous benzaldehyde mediated photoredox C?-heteroarylation, we have identified NHS as a new and efficient mediator without using light. A distinct non-photoredox engaged hydrogen-atom-transfer (HAT) mechanism that used a nitrogen-centered radical cation produced from NHS is initially revealed. Notably, only 5-10 equivalents of ethers as coupling partners are used, which allows for structurally diverse and complex ethers to engage in this process, to create highly medicinally relevant C?-heteroarylated ethers. Furthermore, more structurally diverse heterocyclics can serve as reactants for this process.

SUBMITTER: Liu S 

PROVIDER: S-EPMC6094177 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other