Regioselective activation of benzocyclobutenones and dienamides lead to anti-Bredt bridged-ring systems by a [4+4] cycloaddition

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 sp2-carbon embedded anti-Bredt bicyclo[5.3.1] skeletons through the Rh-catalyzed C1–C8 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.

Rh-Catalyzed Cascade C–C/Colefin–H Activations and Mechanistic Insight

“…The deuterium was transferred intramolecularly from the olefinic position to the methyl group (eq 2, Scheme ). The 50% incorporation of deuterium was attributed to the scrambling of transiently formed Cl 2 (nbd)­Rh-D from DCl and (nbd)­RhCl with nbd . However, the deuterium transfer undoubtedly demonstrated that C olefin –H can be selectively activated and is in good agreement with the mechanism.…”

Catalytic [4+2]- and [4+4]-cycloaddition using furan-fused cyclobutanone as a privileged C4 synthon

“…1b ) 43 – 47 . However, challenges remain in this area, including: (1) derivatization of BCBs to those that are heteroarene-fused remains elusive; (2) these transformations are mainly limited to the intramolecular versions due to the high reactivity of in situ formed metallacycle species; (3) the unsaturated units for [4 + 2]-cycloaddition have been primarily restricted to alkenes 48 – 51 , alkynes 52 – 55 , carbonyls 56 , oximes 57 , allenes/1,3-dienes 58 , and heteroarenes 59 , but imines and other readily available nucleophilic reagents are still unexploited; (4) only few catalytic asymmetric methods have been reported, and the asymmetric synthesis of chiral (hetero)arene fused heterocycles represents a significant challenge 60 – 65 . To address these limitations, the development of a platform molecule as a versatile C4 synthon is a pivotal aspect.…”

Organo-photoredox catalyzed gem-difluoroallylation of ketone-derived dihydroquinazolinones via C(sp3)–C bond and C(sp3)–F bond cleavage

“…Recently, transition-metal catalyzed C(sp 3 )–C bond activation and functionalization of ketones have received remarkable attraction, despite the substrate scope being limited to either 1,3-dicarbonyl 14 or strained motifs. 11 d ,15 Additionally, directing groups 16 and/or high temperatures 17 are often required for successful activation. Most recently, photochemistry has been utilized as an efficient method to address these issues, and cyclic ketone-derived oxime esters and oxime carboxylic acids have been successfully installed with α-trifluoromethyl alkenes to forge gem -difluoroalkenes.…”