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Herein we describe the use of synergistic Pd and Cu catalysis for stereodivergent coupling reactions between 1,3-dienes and aldimine esters. By using different enantiomers of the two metal catalysts, all four stereoisomers of the coupling products, which have two vicinal stereocenters, could be accessed with high diastereo-and enantioselectivity. This atom-economical cross-coupling reaction has a wide substrate scope and good functional group tolerance. Our work highlights the power of synergistic catalysis for asymmetric coupling reactions involving Pd-hydride catalysts.A s an atom-economical strategy for C−C bond formation, coupling reactions between enols/enolates and unsaturated hydrocarbons with catalysis by transition-metal hydrides (M-H) have been attracting increasing attention. 1 These reactions are initiated by addition of M-H to the unsaturated hydrocarbon to form an electrophilic π-allyl metal intermediate, which reacts with the enolizable carbonyl compound to form a C−C bond (Scheme 1A). Substantial progress on asymmetric versions of these reactions has been made. 2−4 However, controlling the stereochemistry when two contiguous stereocenters are generated by these methods remains a formidable challenge; Dong and co-workers reported the only successful example to date. 5 These investigators developed a cooperative system involving Rh−H and Jacobsen's amine for stereodivergent coupling of aldehydes with alkynes. Inspired by this work, as well as recent advances in Ir-catalyzed stereodivergent allylic alkylation reactions, 6−8 we herein report a protocol for asymmetric coupling reactions between 1,3-dienes and aldimine esters with synergistic catalysis 9 by Pd and Cu; all four possible stereoisomers of the coupling products could be obtained regio-, enantio-, and diastereoselectively by using various combinations of different enantiomers of the two catalysts.Pioneering work by Malcolmson and co-workers demonstrated that Pd-phosphinooxazoline (Pd-PHOX) catalysts can be used to accomplish the addition of various activated Cpronucleophiles to 1,3-dienes with high enantioselectivity. 2d,e However, these investigators did not evaluate less reactive pronucleophiles, 10,11 such as amino acid derivatives. Zhou et al. reported a Ni(0)-catalyzed coupling of 1,3-dienes with simple ketones, but nearly 1:1 mixtures of diastereomers were obtained when two stereocenters were generated. 4 We

The site-specific oxidation of strong C­(sp3)–H bonds is of uncontested utility in organic synthesis. From simplifying access to metabolites and late-stage diversification of lead compounds to truncating retrosynthetic plans, there is a growing need for new reagents and methods for achieving such a transformation in both academic and industrial circles. One main drawback of current chemical reagents is the lack of diversity with regard to structure and reactivity that prevents a combinatorial approach for rapid screening to be employed. In that regard, directed evolution still holds the greatest promise for achieving complex C–H oxidations in a variety of complex settings. Herein we present a rationally designed platform that provides a step toward this challenge using N-ammonium ylides as electrochemically driven oxidants for site-specific, chemoselective C­(sp3)–H oxidation. By taking a first-principles approach guided by computation, these new mediators were identified and rapidly expanded into a library using ubiquitous building blocks and trivial synthesis techniques. The ylide-based approach to C–H oxidation exhibits tunable selectivity that is often exclusive to this class of oxidants and can be applied to real-world problems in the agricultural and pharmaceutical sectors.

The catalysis by a π-allyl-Co/Ni complex has drawn significant attention recently due to its distinct reactivity in reductive Co/Ni-catalyzed allylation reactions. Despite significant success in reaction development, the critical oxidative addition mechanism to form the π-allyl-Co/Ni complex remains unclear. Herein, we present a study to investigate this process with four catalysis-relevant complexes: Co(MeBPy)Br2, Co(MePhen)Br2, Ni(MeBPy)Br2, and Ni(MePhen)Br2. Enabled by an electroanalytical platform, Co(I)/Ni(I) species were found responsible for the oxidative addition of allyl acetate. Kinetic features of different substrates were characterized through linear free-energy relationship (Hammett-type) studies, statistical modeling, and a DFT computational study. In this process, a coordination-ionization-type transition state was proposed, sharing a similar feature with Pd(0)-mediated oxidative addition in Tsuji–Trost reactions. Computational and ligand structural analysis studies support this mechanism, which should provide key information for next-generation catalyst development.

Petroleum hydrocarbons are our major energy source and an important feedstock for the chemical industry. With the exception of combustion, the deep conversion of chemically inert hydrocarbons to more valuable chemicals is of considerable interest. However, two challenges hinder this conversion. One is the regioselective activation of inert carbon–hydrogen (C–H) bonds. The other is designing a pathway to realize this complicated conversion. In response to the two challenges, a multistep bioelectrocatalytic system was developed to realize the one-pot deep conversion from heptane to N-heptylhepan-1-imine under mild conditions. First, in this enzymatic cascade, a bioelectrocatalytic C–H bond oxyfunctionalization step based on alkane hydroxylase (alkB) was applied to regioselectively convert heptane to 1-heptanol. By integrating subsequent alcohol oxidation and bioelectrocatalytic reductive amination steps based on an engineered choline oxidase (AcCO6) and a reductive aminase (NfRedAm), the generated 1-heptanol was successfully converted to N-heptylhepan-1-imine. The electrochemical architecture provided sufficient electrons to drive the bioelectrocatalytic C–H bond oxyfunctionalization and reductive amination steps with neutral red (NR) as electron mediator. The highest concentration of N-heptylhepan-1-imine achieved was 0.67 mM with a Faradaic efficiency of 45% for C–H bond oxyfunctionalization and 70% for reductive amination. Hexane, octane, and ethylbenzene were also successfully converted to the corresponding imines. Via regioselective C–H bond oxyfunctionalization, intermediate oxidation, and reductive amination, the bioelectrocatalytic hydrocarbon deep conversion system successfully realized the challenging conversion from inert hydrocarbons to imines that would have been impossible by using organic synthesis methods and provided a new methodology for the comprehensive conversion and utilization of inert hydrocarbons.

While the oxidative addition of Ni­(I) to aryl iodides has been commonly proposed in catalytic methods, an in-depth mechanistic understanding of this fundamental process is still lacking. Herein, we describe a detailed mechanistic study of the oxidative addition process using electroanalytical and statistical modeling techniques. Electroanalytical techniques allowed rapid measurement of the oxidative addition rates for a diverse set of aryl iodide substrates and four classes of catalytically relevant complexes (Ni­(MeBPy), Ni­(MePhen), Ni­(Terpy), and Ni­(BPP)). With >200 experimental rate measurements, we were able to identify essential electronic and steric factors impacting the rate of oxidative addition through multivariate linear regression models. This has led to a classification of oxidative addition mechanisms, either through a three-center concerted or halogen-atom abstraction pathway based on the ligand type. A global heat map of predicted oxidative addition rates was created and shown applicable to a better understanding of the reaction outcome in a case study of a Ni-catalyzed coupling reaction.

Redox catalysis has been broadly utilized in electrochemical synthesis due to its kinetic advantages over direct electrolysis. The appropriate choice of redox mediator can avoid electrode passivation and overpotential, which...

First‐row transition metal complexes have garnered attention due to their ability to activate aliphatic halides for catalytic cross‐coupling reactions. However, mechanistic investigation of these systems is challenging as a consequence of difficulties associated with preparing the relevant metal complexes and the resultant poor stability of such intermediates for subsequent analytical interrogation. In this context, we have developed a platform to rapidly measure kinetic data using electroanalytical methods, which facilitates a wide range of physical organic studies. As a result, we have investigated and compared the reaction of benzyllic halides with electrogenerated MnI(PyBox)Cl, FeI(Pyrox)OTf, CoI(Pyrox)Br, CoI(PyBox)Br, NiI(Phox)Br complexes. The experimental results support a unified inner‐sphere halogen atom abstraction mechanism for these different complexes while also providing the ability to directly compare through multivariate linear regression analyses the subtle differences imparted by metal/ligand combinations. The information gleaned by this study has implications why certain metal complexes are matched to oxidative addition processes relevant in catalytic processes.