Quaternary Carbon Editing Enabled by Sequential Palladium Migration.

Peripheral functionalization of a quaternary carbon via C(sp3)-H bond activation has made significant progress in recent years. However, direct editing of a quaternary carbon through Csp3-Csp3 bond cleavage and refunctionalization of nonstrained acyclic molecules remain underexploited. Herein we report a reaction in which a methyl group attached to a quaternary carbon is shifted to its neighboring secondary carbon with concurrent oxidation of the quaternary C-C single bond to the C═C double bond. Specifically, morpholinyl amide of 2,2-dimethyl alkanoic acids is converted to 2-methylene-3-methyl alkanoic acid derivatives in the presence of a catalytic amount of palladium acetate, Selectfluor and sodium carbonate. Control experiments suggest that the reaction proceeds via a sequence of selective C(sp3)-H activation of the methyl group, oxidation of the resulting C(sp3)-PdII to PdIV intermediate followed by unprecedented 1,3-PdIV migration, 1,2-methyl/PdIV dyotropic rearrangement and finally, ß-Hydride elimination. In this domino process, palladium migrates successively from the primary to the secondary and finally to the quaternary carbon, leading to the concurrent functionalization of a primary, a secondary, and a quaternary carbon.

Arylative Ring Expansion of 3-Vinylazetidin-3-Ols and 3-Vinyloxetan-3-Ols to Dihydrofurans by Dual Palladium and Acid Catalysis.

In contrast to the well-studied 1-vinylcyclobutanols, the reactivity of 3-vinylazetidin-3-ols 1 and 3-vinyloxetan-3-ols 2 under transition metal catalysis remains largely unexplored. We report herein their unique reactivity under dual palladium and acid catalysis. In the presence of a catalytic amount of Pd(OAc)2(PPh3)2, AgTFA and triflic acid, the reaction of 1 or 2 with aryl iodides affords 2,3,4-trisubstituted dihydrofurans, which are valuable heterocycles in organic synthesis. Mechanistic studies reveal that this arylative ring-expansion reaction proceeds via a domino process involving Heck arylation of alkene, acid-catalyzed transposition of allylic alcohol and ring opening of the azetidine/oxetane by an internal hydroxyl group.

Modular Synthesis of Benzocyclobutenes via Pd(II)-Catalyzed Oxidative [2+2] Annulation of Arylboronic Acids with Alkenes.

Benzocyclobutenes (BCBs) are highly valuable compounds in organic synthesis, medicinal chemistry, and materials science. However, catalytic modular synthesis of functionalized BCBs from easily accessible starting materials remains limited. We report herein an efficient synthesis of diversely functionalized BCBs by a Pd(II)-catalyzed formal [2+2] annulation between arylboronic acids and alkenes in the presence of N-fluorobenzenesulfonimide (NFSI). An intermolecular carbopalladation followed by palladium oxidation, intramolecular C(sp2)-H activation by a transient C(sp3)-Pd(IV) species, and selective carbon-carbon (C-C) bond-forming reductive elimination from a high-valent five-membered palladacycle is proposed to account for the reaction outcome. Kinetically competent oxidation of alkylPd(II) to alkylPd(IV) species is important to avoid the formation of a Heck adduct. The reaction forges two C-C bonds of the cyclobutene core and is compatible with a wide range of functional groups. No chelating bidentate directing group in the alkene part is needed for this transformation.

Highly enantioselective synthesis of trifluoromethyl cyclopropanes by using Ru(ii)-Pheox catalysts.

An asymmetric synthesis of various trifluoromethyl cyclopropanes from olefins, such as vinyl ferrocene, vinyl ethers, vinyl amines, vinyl carbamates and dienes, was achieved by using Ru(ii)-Pheox catalysts. This catalytic system can function at a low catalyst loading (3 mol%) compared with those reported previously, and the desired cyclopropane products are obtained in high yields with excellent diastereoselectivity (up to >99 : 1) and enantioselectivity (up to 97% ee).