Dual-Catalytic Structural Isomerisation as a Route to α-Arylated Ketones.

Isomerisation reactions provide streamlined routes to organic compounds which are otherwise hard to directly synthesise. The most common forms are positional, geometrical or stereochemical isomerisations which involve the relocation of a double bond or a change in relative location of groups in space. In contrast, far fewer examples of structural (or constitutional) isomerisation exist where the connectivity between atoms is altered. The development of platforms capable of such rearrangement poses a unique set of challenges because chemical bonds must be selectively cleaved, and new ones formed without overall addition or removal of atoms. Here, we show that a dual catalytic system can enable the structural isomerisation of readily available allylic alcohols into more challenging-to-synthesise α-arylated ketones via a H-atom transfer initiated semi-pinacol rearrangement. Key to our strategy is the combination of a cobalt catalyst and photocatalyst under reductive, protic conditions which allows intermediates to propagate catalytic turnover. By providing an unusual disconnection to structural motifs which are difficult to access through direct arylation, we anticipate inspiring other advanced catalytic isomerisation strategies that will further retrosynthetic logic for complex molecule synthesis.

Photoinduced Cobalt Catalysis for the Reductive Coupling of Pyridines and Dienes Enabled by Paired Single-Electron Transfer.

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.

Catalytic Atroposelective Electrophilic Amination of Indoles.

Reported here is the first catalytic atroposelective electrophilic amination of indoles, which delivers functionalized atropochiral N-sulfonyl-3-arylaminoindoles with excellent optical purity. This reaction was furnished by 1,6-nucleophilic addition to p-quinone diimines. Control experiments suggest an ionic mechanism that differs from the radical addition pathway commonly proposed for 1,6-addition to quinones. The origin of 1,6-addition selectivity was investigated through computational studies. Preliminary studies show that the obtained 3-aminoindoles atropisomers exhibit anticancer activities. This method is valuable with respect to enlarging the toolbox for atropochiral amine derivatives.

Hemin-Catalyzed Oxidative Phenol-Hydrazone [3+3] Cycloaddition Enables Rapid Construction of 1,3,4-Oxadiazines.

Herein, we present a hemin-catalyzed oxidative phenol-hydrazone [3+3] cycloaddition that accommodates a broad spectrum of N-arylhydrazones, a class of less exploited 1,3-dipoles due to their significant Lewis basicity and weak tendency to undergo 1,2-prototropy to form azomethine imines. It renders expedient assembly of diversely functionalized 1,3,4-oxadiazines with excellent atom and step economy. Preliminary mechanistic studies point to the involvement of a one-electron oxidation pathway, which likely differs from the base-promoted aerobic oxidative scenario.