Imine as a linchpin approach for meta-C-H functionalization.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33654108.
- Also identified by DOI 10.1038/s41467-021-21633-2 and PMC identifier 7925593.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Despite the widespread applications of C-H functionalization, controlling site selectivity remains a significant challenge. Covalently attached directing groups (DGs) served as ancillary ligands to ensure ortho-, meta- and para-C-H functionalization over the last two decades. These covalently linked DGs necessitate two extra steps for a single C-H functionalization: introduction of DG prior to C-H activation and removal of DG post-functionalization. Here we report a temporary directing group (TDG) for meta-C-H functionalization via reversible imine formation. By overruling facile ortho-C-H bond activation by imine-N atom, a suitably designed pyrimidine-based TDG successfully delivered selective meta-C-C bond formation. Application of this temporary directing group strategy for streamlining the synthesis of complex organic molecules without any necessary pre-functionalization at the meta position has been explored.