H-bonded reusable template assisted para-selective ketonisation using soft electrophilic vinyl ethers.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30181575.
- Also identified by DOI 10.1038/s41467-018-06018-2 and PMC identifier 6123475.
- 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
In nature, enzymatic pathways generate C<sub>aryl</sub>-C(O) bonds in a site-selective fashion. Synthetically, C<sub>aryl</sub>-C(O) bonds are synthesised in organometallic reactions using prefunctionalized substrate materials. Electrophilic routes are largely limited to electron-rich systems, non-polar medium, and multiple product formations with a limited scope of general application. Herein we disclose a directed para-selective ketonisation technique of arenes, overriding electronic bias and structural congestion, in the presence of a polar protic solvent. The concept of hard-soft interaction along with in situ activation techniques is utilised to suppress the competitive routes. Mechanistic pathways are investigated both experimentally and computationally to establish the hypothesis. Synthetic utility of the protocol is highlighted in formal synthesis of drugs, drug cores, and bioactive molecules.