A direct decarboxylative strategy for the generation of aza‐o‐quinone methides (aza‐o‐QMs) by N‐heterocyclic carbene (NHC) catalysis has been discovered and explored. This process requires no stoichiometric additives in contrast with current approaches. Aza‐o‐QMs react with trifluoromethyl ketones through a formal [4+2] manifold to access highly enantioenriched dihydrobenzoxazin‐4‐one products, which can be converted to dihydroquinolones through an interesting stereoretentive aza‐Petasis–Ferrier rearrangement sequence. Complementary dispersion‐corrected density functional theory (DFT) studies provided an accurate prediction of the reaction enantioselectivity and lend further insight to the origins of stereocontrol. Additionally, a computed potential energy surface around the major transition structure suggests a concerted asynchronous mechanism for the formal annulation.

Axially chiral phenols are attractive targets in organic synthesis.T his motif is central to many natural products and widely used as precursors to,ordirectly,aschiral ligands and catalysts.D espite their utility few simple catalytic methods are available for their synthesis in high enantiopurity.Herein the atropselective acylation of ar ange of symmetric biaryl diols is investigated using isothiourea catalysis.S tudies on amodel biaryl diol substrate shows that the high product er observed in the process is ar esult of two successive enantioselective reactions consisting of an initial enantioselective desymmetrization coupled with as econd chiroablative kinetic resolution. Extension of this process to ar ange of substrates, including achallenging tetraorthosubstituted biaryl diol, led to highly enantioenriched products (14 examples,u pt o9 8:2e r), with either HyperBTM or BTM identified as the optimal catalyst depending upon the substitution pattern within the substrate.Computation has been used to understand the factors that lead to high enantiocontrol in this process,w ith maintenance of planarity to maximizea1,5-S···O interaction within the key acyl ammonium intermediate identified as the major feature that determines atropselective acylation and thus product enantioselectivity.

Transition metal-catalyzed C–H functionalization and decarboxylative coupling are two of the most notable synthetic strategies developed in the last 30 years. Herein, we connect these two reaction pathways using bases and a simple Pd-based catalyst system to promote a para -selective C–H functionalization reaction from benzylic electrophiles. Experimental and computational mechanistic studies suggest a pathway involving an uncommon Pd-catalyzed dearomatization of the benzyl moiety followed by a base-enabled rearomatization through a formal 1,5-hydrogen migration. This reaction complements “C–H activation” strategies that convert inert C–H bonds into C–metal bonds prior to C–C bond formation. Instead, this reaction exploits an inverted sequence and promotes C–C bond formation prior to deprotonation. These studies provide an opportunity to develop general para -selective C–H functionalization reactions from benzylic electrophiles and show how new reactive modalities may be accessed with careful control of reaction conditions.

A novel strategy for the stereospecific Pd-catalyzed acylative cross-coupling of enantiomerically enriched alkylboron compounds has been developed. The protocol features an extremely high level of enantiospecificity to allow facile access to synthetically challenging and valuable chiral ketones and carboxylic acid derivatives. The use of a sterically encumbered and electronrich phosphine ligand proved to be crucial for the success of the reaction. Furthermore, on the basis of experimental and computational studies, a unique mechanism for the transmetalation, assisted by the noncovalent interactions of the C(sp 3 )-based organoboron reagent, has been identified.

The combined experimental and computational study on palladium-catalyzed regioselective C–H functionalization of O-coordinating directing groups with epoxides is described.