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An iridium-catalyzed remote site-switchable hydroarylation of alkenes was reported, delivering the products functionalized at the subterminal methylene and terminal methyl positions on an alkyl chain controlled by two different ligands, respectively, in good yields and with good to excellent site-selectivities. The catalytic system showed good functional group tolerance and a broad substrate scope, including unactivated and activated alkenes. More importantly, the regioconvergent transformations of mixtures of isomeric alkenes were also successfully realized. The results of the mechanistic studies demonstrate that the reaction undergoes a chain-walking process to give an [Ar-Ir-H] complex of terminal alkene. The subsequent processes proceed through the modified Chalk-Harrod-type mechanism via the migratory insertion of terminal alkene into the Ir-C bond followed by C-H reductive elimination to afford the hydrofunctionalization products site-selectively., (© 2023 Wiley-VCH GmbH.)

The allylic alcohol structural motif is prevalent in many important molecules and valuable building blocks. The rearrangement reaction is one of the most important transformations, however there are only a few reports for the 1,3-rearrangement of allylic alcohols. Herein, a 1,3-rearrangement of allylic alcohols catalyzed by an Ir(III) dihydride complex is described. This reaction could provide the corresponding less accessible allylic alcohols regio- and stereoselectively from readily available E/Z mixtures of the substrates. Furthermore, a tandem alkene isomerization followed by 1,3-rearrangement of homoallylic alcohols was also realized. In addition, this rearrangement reaction could be used to synthesize the natural product Navenone B. Mechanistic investigation indicated that the reaction pathway involved a π-allyl-Ir(V) intermediate and that the dihydride in the iridium catalyst acts as a hydrogen switch to modulate the valence of the iridium center., (© 2023 Wiley-VCH GmbH.)

The catalytic asymmetric synthesis of the anti-COVID-19 drug Remdesivir has been realized by the coupling of the P-racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst used is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proceed smoothly with high reactivity and excellent stereoselectivity (96 % conv., 22:1 S P :R P ). Mechanistic studies showed that this DyKAT is a first-order visual kinetic reaction dependent on the catalyst concentration. The unique chiral bicyclic imidazole skeleton and carbamate substituent of the catalyst are both required for the racemization process, involving the phosphoryl chloride, and subsequent stereodiscriminating step. A 10 gram scale reaction was also conducted with comparably excellent results, showing its potential for industrial application., (© 2020 Wiley-VCH GmbH.)

In this report, a palladium-catalyzed redox-relay Heck process to access optically active alkenylated α,β-unsaturated lactams is described. Under mild reaction conditions, electron-deficient alkenyl triflates and electron-rich alkenyl iodonium salts undergo enantioselective and site-selective coupling with enelactams to deliver the products in high yields and excellent enantioselectivities. Furthermore, the products allow facile access to natural products such as (+)-calvine and (+)-2-epicalvine in addition to the bioactive molecule aza-goniothalamin., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A palladium-catalyzed enantioselective redox-relay Heck reaction of 2-indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine-oxazoline ligand. Tuning the electronics of the indole, through judicious choice of N-protecting group, is required to ensure selective β-hydride elimination away from the indole core. Utility of this method is highlighted in a modular formal synthesis of an S1P 1 agonist precursor developed by Merck., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)