Regioselective activation of benzocyclobutenones and dienamides lead to anti-Bredt bridged-ring systems by a [4+4] cycloaddition.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34021154.
- Also identified by DOI 10.1038/s41467-021-23344-0 and PMC identifier 8140143.
- 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
To the best of our knowledge, bridgehead carbon benzofused-bridged ring systems have previously not been accessible to the synthetic community. Here, we describe a formal type-II [4 + 4] cycloaddition approach that provides fully sp<sup>2</sup>-carbon embedded anti-Bredt bicyclo[5.3.1] skeletons through the Rh-catalyzed C<sub>1</sub>-C<sub>8</sub> activation of benzocyclobutenones (BCBs) and their coupling with pedant dienamides. Variously substituted dienamides have been coupled with BCBs to provide a range of complex bicyclo[5.3.1] scaffolds (>20 examples, up to 89% yield). The bridged rings were further converted to polyfused hydroquinoline-containing tetracycles via a serendipitously discovered transannular 1,5-hydride shift/Prins-like cyclization/Schmidt rearrangement cascade.