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Abstract Hybrid fused two-dimensional/three-dimensional (2D/3D) rings are important pharmacophores in drugs owing to their unique structural and physicochemical properties. Preparation of these strained ring systems often requires elaborate synthetic effort and exhibits low efficiency, thus representing a limiting factor in drug discovery. Here, we report two types of energy-transfer-mediated cascade dearomative [2 + 2] cycloaddition/rearrangement reactions of quinoline derivatives with alkenes, which provide a straightforward avenue to 2D/3D pyridine-fused 6−5−4−3- and 6−4−6-membered ring systems. Notably, this energy-transfer-mediated strategy features excellent diastereoselectivity that bypasses the general reactivity and selectivity issues of photochemical [2 + 2] cycloaddition of various other aromatics. Tuning the aza-arene substitutions enabled selective diversion of the iridium photocatalysed energy transfer manifold towards either cyclopropanation or cyclobutane-rearrangement products. Density functional theory calculations revealed a cascade energy transfer scenario to be operative. 

Reactions that lead to destruction of aromatic ring systems often require harsh conditions and, thus, take place with poor selectivities. Selective partial dearomatization of fused arenes is even more challenging but can be a strategic approach to creating versatile, complex polycyclic frameworks. Herein we describe a general organophotoredox approach for the chemo- and regioselective dearomatization of structurally diverse polycyclic aromatics, including quinolines, isoquinolines, quinoxalines, naphthalenes, anthracenes and phenanthrenes. The success of the method for chemoselective oxidative rupture of aromatic moieties relies on precise manipulation of the electronic nature of the fused polycyclic arenes. Mechanistic studies show that the addition of a hydrogen atom transfer (HAT) agent helps favor the dearomatization pathway over the more thermodynamically downhill aromatization pathway. We show that this strategy can be applied to rapid synthesis of biologically valued targets and late-stage skeletal remodeling en route to complex structures.

 

Although radical formation from a trialkylborane is well documented, the analogous reaction mode is unknown for trihaloboranes. We have discovered the generation of bromine radicals from boron tribromide and simple proton sources, such as water or tert -butanol, under open-flask conditions. Cyclopropanes bearing a variety of substituents were hydro- and deuterio-brominated to furnish anti-Markovnikov products in a highly regioselective fashion. NMR mechanistic studies and DFT calculations point to a radical pathway instead of the conventional ionic mechanism expected for BBr 3 .