Manuel Barday

Selective hydroarylation of dienes has potential to provide swift access to useful building blocks. However, most existing methods rely on dienes stabilised by an aromatic group and transmetallation or nucleophilic attack steps require electron‐rich aryl coupling partners. As such, there are few examples which tolerate wide‐spread heteroarenes such as pyridine. Whilst allylic C−H functionalisation could be considered an alternative approach, the positional selectivity of unsymmetrical substrates is hard to control. Here, we report a general approach for selective hydropyridylation of dienes under mild conditions using metal catalysed hydrogen‐atom transfer. Photoinduced, reductive conditions enable simultaneous formation of a cobalt‐hydride catalyst and the persistent radical of easily‐synthesised pyridyl phosphonium salts. This facilitates selective coupling of dienes in a traceless manner at the C4‐position of a wide‐range of pyridine substrates. The mildness of the method is underscored by its functional‐group tolerance and demonstrated by applications in late‐stage functionalisation. Based on a combination of experimental and computational studies, we propose a mechanistic pathway which proceeds through non‐reversible hydrogen‐atom transfer (HAT) from a cobalt hydride species which is uniquely selective for dienes in the presence of other olefins due to a much higher relative barrier associated with olefin HAT.

The design of a NHC‐catalyzed methodology for the straightforward access to hitherto unknown axially chiral N ‐aryl phthalimides has provided a breakthrough in the field of multichirality control. Anticipating a formal (4+2) oxidative annulation, the use of NHC‐derived chiral dienolate as ambident partner toward N ‐aryl maleimides unexpectedly yields original bis ‐succinimide‐type compounds featuring a multichiral architecture with up to four stereogenic centers and two remote chiral axes. The overall pseudo‐three components reaction between an enal and two equivalents of a N ‐aryl maleimide proceeds with excellent enantioselectivity and complete diastereoselectivity. This study illustrates the high synthetic potential of chiral NHC‐activated dienolates for the rapid and highly diastereo‐ and enantioselective preparation of underexplored atropisomers in the pentatomic series, featuring multiple stereogenic elements including challenging C sp 2 −N chiral axes. The practicality of this reaction is highlighted by a broad substrate scope and a scaled‐up synthesis. Moreover, the easy base‐induced transformation of the chiral bis ‐succinimide precursors allows to prepare the initially planned N ‐aryl phthalimide atropisomers with excellent retention of enantiopurity. magnified image