Redox-Neutral ortho Functionalization of Aryl Boroxines via Palladium/Norbornene Cooperative Catalysis

Abstract

A redox-neutral ortho functionalization of aryl boroxines via palladium/ norbornene cooperative catalysis is developed. The ortho amination and acylation are achieved with carboxylic acid anhydrides and O-benzoyl hydroxylamines as an electrophile, respectively, whereas protonation occurs at the ipso position. This transformation avoids using either extra oxidants and reductants or stoichiometric bases and acids. In addition, orthogonal chemoselectivity between aryl iodide and boroxine moieties is demonstrated for pathway divergence. HIGHLIGHTS First redox-neutral direct ortho functionalization of aryl boroxines Proton as the second electrophile coupled at the ipso position Avoiding stoichiometric bases in the Pd/NBE catalysis Orthogonal chemoselectivity between aryl iodide and boroxine moieties Li et al., Chem 5, 929-939 April 11, SUMMARYPalladium/norbornene (Pd/NBE) cooperative catalysis, also known as the Catellani reaction, has become an increasingly useful method for site-selective arene functionalization; however, certain constraints still exist because of its intrinsic mechanistic pathway. Herein, we report a redox-neutral ortho functionalization of aryl boroxines via Pd/NBE catalysis. An electrophile, such as carboxylic acid anhydrides or O-benzoyl hydroxylamines, is coupled at the boroxine ortho position, and a proton as the second electrophile is introduced at the ipso position. This reaction does not require extra oxidants or reductants and avoids stoichiometric bases or acids, thereby tolerating a wide range of functional groups. In particular, orthogonal chemoselectivity between aryl iodide and boroxine moieties is demonstrated, which could be used to control reaction sequences. Finally, a deuterium-labeling study supports the ipso protonation pathway. This unique mechanistic feature could inspire the development of a new class of Pd/NBE-catalyzed transformations.

Redox-neutral ortho-C–H amination of pinacol arylborates via palladium(ii)/norbornene catalysis for aniline synthesis

“…These experimental results indicated that both the protons from the ortho -C–H of pinacol arylborate and the adventitious water in the reaction system are the sources for the Catellani termination step, but not the solvent DMSO. The reduction of the deuterium incorporation ratio in eqn (C) and (D) was probably due to the facile H–D exchange with water in the reaction system 8. Thus, these results support the redox-neutral ipso -protonation mechanism proposed in Scheme 1C.…”

“…Additionally, allowing us to perform the reaction in air is very attractive from both the practical and economic perspective. Moreover, this process does not require any phosphine or arsine ligand7b,c which is pivotal for previous palladium-catalyzed aminations 3–5,7a,8. Overall, these practical features make this reaction amenable for industry.…”

“…Until recently, the group of Dong reported elegant related research (Scheme 1D). 8 As shown in Scheme 1C, it is surmised that the reaction is initiated through transmetalation between the palladium( ii ) catalyst and arylboronic acid derivative 1 to deliver the aryl palladium( ii ) intermediate I . The following steps involve insertion of NBE to I and subsequent ortho -C–H activation, generating the aryl/NBE palladacycle complex (ANP) II .…”

Catalytic Atroposelective Catellani Reaction Enables Construction of Axially Chiral Biaryl Monophosphine Oxides

“…Based on the previous reports on Pd/NBE-catalyzed aryl halide-involved three-component Catellani reaction [50][51][52][53][54][55][56] and our experience on catalytic asymmetric construction of atropisomeric biaryls, 59 reaction mechanism and atroposelectivity of the reported Pd-catalyzed Catellani reaction. As shown in Figure 2, the reaction starts from a solvent coordinated Pd species CP1, which can react with iodonaphthalene reactant 1a through an oxidative addition process via transition-state TS1 with an activation free energy of 8.6 kcal/mol.…”

“…In Gu et al's elegant work, 49 the chirality installation took place in the last cross-coupling step involving an achiral palladium (Pd) species. Motivated by the recent progress in Pd/norbornene (NBE) cooperative catalysis in which the functionalization of both ortho-and ipso-carbons of the starting arylhalides could be readily achieved, [50][51][52][53][54][55][56] especially the recent Pd/chiral NBE catalysis which has been successfully employed in asymmetric synthesis, 50,51 we envisioned a strategy for the establishment of optically active atropisomeric biaryl monophosphine oxides using a Pd/chiral NBE catalytic system from aryl iodide and a phosphine oxide-containing aryl bromide via the axially chiral Pd(II) intermediate in Figure 1c. Further trapping by the terminating nucleophile will render a modular platform for the divergent synthesis of enantioenriched biaryl atropisomers (Figure 1c).…”