Abstraction of Hydride from Alkanes and Dihydrogen by the Perfluorotrityl Cation.

Lewis acids play a central role in a large variety of chemical transformations. The reactivity of the strongest Lewis acids is typically studied in the context of affinity towards hard bases, such as fluoride or oxygenous species. Carbocations can be viewed as soft Lewis acids, possessing significant affinity for softer bases, such as hydride.

Ring expansion of indene by photoredox-enabled functionalized carbon-atom insertion.

Skeletal editing has received unprecedented attention as an emerging technology for the late-stage manipulation of molecular scaffolds. The direct achievement of functionalized carbon-atom insertion in aromatic rings is challenging. Despite ring-expanding carbon-atom insertion reactions, such as the Ciamician-Dennstedt re-arrangement, being performed for more than 140 years, only a few relevant examples of such transformations have been reported, with these limited to the installation of halogen, ester and phenyl groups.

Photochemical phosphorus-enabled scaffold remodeling of carboxylic acids.

The excitation of carbonyl compounds by light to generate radical intermediates has historically been restricted to ketones and aldehydes; carboxylic acids have been overlooked because of high energy requirements and low quantum efficiency. A successful activation strategy would necessitate a bathochromic shift in the absorbance profile, an increase in triplet diradical lifetime, and ease of further functionalization. We present a single-flask transformation of carboxylic acids to acyl phosphonates that can access synthetically useful triplet diradicals under visible light or near-ultraviolet irradiation.

Stereoselective Fe-Catalyzed Decoupled Cross-Couplings: Chiral Vinyl Oxazolidinones as Effective Radical Lynchpins for Diastereoselective C(sp)-C(sp) Bond Formation.

Modular, catalytic, and stereoselective methods for the dicarbofunctionalization of alkenes can streamline the synthesis of chiral active pharmaceutical ingredients (APIs) and agrochemicals. However, despite the inherent attractive properties of iron as catalysts for practical pharmaceutical synthesis (i.e.

Nitrogen-to-functionalized carbon atom transmutation of pyridine.

The targeted and selective replacement of a single atom in an aromatic system represents a powerful strategy for the rapid interconversion of molecular scaffolds. Herein, we report a pyridine-to-benzene transformation nitrogen-to-carbon skeletal editing. This approach proceeds a sequence of pyridine ring-opening, imine hydrolysis, olefination, electrocyclization, and aromatization to achieve the desired transmutation.

Fe-Catalyzed Fluoroalkyl(hetero)arylation of Vinyl Azaarenes: Rapid and Modular Synthesis of Unsymmetrical 1,1-Bis(hetero)arylalkanes.

In contrast to transition-metal-catalyzed difunctionalization of activated alkenes, selective alkylarylation of vinyl azaarenes is underdeveloped. Consequently, the lack of modular and rapid syntheses of 1,1-bis(hetero)arylalkanes limits their exploration in medicinal chemistry. Herein we report a protocol using commercially available iron salts, bisphosphine ligands, fluoroalkyl halides, and Grignard reagents that enables the selective 1,2-fluoroalkyl(hetero)arylation of vinyl azaarenes.

Molecular Ball Joints: Mechanochemical Perturbation of Bullvalene Hardy-Cope Rearrangements in Polymer Networks.

The solution-state fluxional behavior of bullvalene has fascinated physical organic and supramolecular chemists alike. Little effort, however, has been put into investigating bullvalene applications in bulk, partially due to difficulties in characterizing such dynamic systems. To address this knowledge gap, we herein probe whether bullvalene Hardy-Cope rearrangements can be mechanically perturbed in bulk polymer networks.

Evidence for Dearomatizing Spirocyclization and Dynamic Effects in the Quasi-stereospecific Nitrogen Deletion of Tetrahydroisoquinolines.

Selectivity in organic chemistry is generally presumed to arise from energy differences between competing selectivity-determining transition states. However, in cases where static density functional theory (DFT) fails to reproduce experimental product distributions, dynamic effects can be examined to understand the behavior of more complex reaction systems. Previously, we reported a method for nitrogen deletion of secondary amines which relies on the formation of isodiazene intermediates that subsequently extrude dinitrogen with concomitant C-C bond formation via a caged diradical.

Monodentate Phosphinoamine Nickel Complex Supported on a Metal-Organic Framework for High-Performance Ethylene Dimerization.

Ethylene dimerization is an efficient industrial chemical process to produce 1-butene, with demanding selectivity and activity requirements on new catalytic systems. Herein, a series of monodentate phosphinoamine-nickel complexes immobilized on UiO-66 are described for ethylene dimerization. These catalysts display extensive molecular tunability of the ligand similar to organometallic catalysis, while maintaining the high stability attributed to the metal-organic framework (MOF) scaffold.

Mechanism of -Selective Allylic Functionalization via Thianthrenium Salts.

A detailed mechanistic study of the -selective allylic functionalization via thianthrenium salts is presented. Kinetic analyses, deuterium labeling experiments, and computational methods are used to rationalize the observed reactivity and selectivity. We find that the reaction proceeds via a rate-determining and stereodetermining allylic deprotonation of an alkenylthianthrenium species.

Light-Induced Living Polymer Networks with Adaptive Functional Properties.

The advent of covalent adaptable networks (CANs) through the incorporation of dynamic covalent bonds has led to unprecedented properties of macromolecular systems, which can be engineered at the molecular level. Among the various types of stimuli that can be used to trigger chemical changes within polymer networks, light stands out for its remote and spatiotemporal control under ambient conditions. However, most examples of photoactive CANs need to be transparent and they exhibit slow response, side reactions, and limited light penetration.

γ-Amino Alcohols via Energy Transfer Enabled Brook Rearrangement.

In the long-standing quest to synthesize fundamental building blocks with key functional group motifs, photochemistry in the recent past has comprehensively established its attractiveness. Amino alcohols are not only functionally diverse but are ubiquitous in the biologically active realm of compounds. We developed bench-stable bifunctional reagents that could then access the sparsely reported γ-amino alcohols directly from feedstock alkenes through energy transfer (EnT) photocatalysis.

Cyclopropenimine-Mediated CO Activation for the Synthesis of Polyurethanes and Small-Molecule Carbonates and Carbamates.

Carbon dioxide (CO) is an abundant C1 feedstock with tremendous potential to produce versatile building blocks in synthetic applications. Given the adverse impact of CO on the atmosphere, it is of paramount importance to devise strategies for upcycling it into useful materials, such as polymers and fine chemicals. To activate such stable molecule, superbases offer viable modes of binding to CO.

Linear and Nonlinear Optical Properties of All- and All- Poly(-phenylenevinylene).

Poly(-phenylenevinylene) (PPV) is a staple of the family of conjugated polymers with desirable optoelectronic properties for applications including light-emitting diodes (LEDs) and photovoltaic devices. Although the significant impact of olefin geometry on the steady-state optical properties of PPVs has been extensively studied, PPVs with precise stereochemistry have yet to be investigated using nonlinear optical spectroscopy for quantum sensing, as well as light harvesting for biological applications. Herein, we report our investigation of the influence of olefin stereochemistry on both linear and nonlinear optical properties through the synthesis of all- and all- PPV copolymers.

Site-Selective Electrochemical Arene C-H Amination.

Here we present the discovery and development of a highly selective aromatic C-H amination reaction. This electrochemical strategy involves a cathodic reduction process that generates highly electrophilic dicationic -centered radicals that can efficiently engage in aromatic C-H functionalization and channel the regioselectivity of the aromatic substitution. The nitrogen-radical cation-pi interaction with arenes used throughout nature leads to a charge transfer mechanism, with subsequent aromatic C-N bond formation.

Selective 1,2-Hydroarylation(Alkenylation) of gem-Difluoroalkenes to Access (-CF H) Motifs.

An emerging class of C-C coupling transformations that furnish drug-like building blocks involves catalytic hydrocarbonation of alkenes. However, despite notable advances in the field, hydrocarbon addition to gem-difluoroalkenes without additional electronic activation remains largely unsuccessful. This owes partly to poor reactivity and the propensity of difluoroalkenes to undergo defluorinative side reactions.

Expanding the chemical space of enol silyl ethers: catalytic dicarbofunctionalization enabled by iron catalysis.

Enol silyl ethers are versatile, robust, and readily accessible substrates widely used in chemical synthesis. However, the conventional reactivity of these motifs has been limited to classical two electron (2-e) enolate-type chemistry with electrophilic partners or as radical acceptors in one electron (1-e) reactivity leading, in both cases, to exclusive α-monofunctionalization of carbonyls. Herein we describe a mild, fast, and operationally simple one-step protocol that combines readily available fluoroalkyl halides, silyl enol ethers, and, for the first time, hetero(aryl) Grignard reagents to promote selective dicarbofunctionalization of enol silyl ethers.

Iron-Catalyzed Enantioselective Multicomponent Cross-Couplings of α-Boryl Radicals.

Despite recent interest in the development of iron-catalyzed transformations, methods that use iron-based catalysts capable of controlling the enantioselectivity in carbon-carbon cross-couplings are underdeveloped. Herein, we report a practical and simple protocol that uses commercially available and expensive iron salts in combination with chiral bisphosphine ligands to enable the regio- and enantioselective (up to 91:9) multicomponent cross-coupling of vinyl boronates, (fluoro)alkyl halides, and Grignard reagents. Preliminary mechanistic studies are consistent with rapid formation of an α-boryl radical followed by radical addition to monoaryl bisphosphine-Fe(II) and subsequent enantioselective inner-sphere reductive elimination.

Programmable late-stage functionalization of bridge-substituted bicyclo[1.1.1]pentane bis-boronates.

Modular functionalization enables versatile exploration of chemical space and has been broadly applied in structure-activity relationship (SAR) studies of aromatic scaffolds during drug discovery. Recently, the bicyclo[1.1.

Rhodium-Catalyzed Asymmetric Synthesis of 1,2-Disubstituted Allylic Fluorides.

Although there are many methods for the asymmetric synthesis of monosubstituted allylic fluorides, construction of enantioenriched 1,2-disubstituted allylic fluorides has not been reported. To address this gap, we report an enantioselective synthesis of 1,2-disubstituted allylic fluorides using chiral diene-ligated rhodium catalyst, Et N ⋅ 3HF as a source of fluoride, and Morita Baylis Hillman (MBH) trichloroacetimidates. Kinetic studies show that one enantiomer of racemic MBH substrate reacts faster than the other.

Regioselective Fluoroalkylarylation of Enamides Enabled by an Iron-Catalyzed Multicomponent Radical Cross-Coupling Strategy.

Fluoroalkylated compounds are important entities in agrochemicals, pharmaceuticals, and materials. The catalytic dicarbofunctionalization of alkenes represents a powerful strategy for the rapid construction and diversification of compounds. In this vein, multicomponent cross-coupling reactions (MC-CCR) can provide an efficient synthetic route to build molecular complexity.

Experimental and Computational Studies on Cobalt(I)-Catalyzed Regioselective Allylic Alkylation Reactions.

Here, we report the development of cobalt(I)-catalyzed regioselective allylic alkylation reactions of tertiary allyl carbonates with 1,3-dicarbonyl compounds. A family of well-defined tetrahedral cobalt(I) complexes bearing commercially available bidentate bis(phosphine) ligands [(P,P)Co(PPh )Cl] are synthesized and explored as catalysts in allylic alkylation reactions. The catalyst [(dppp)Co(PPh )Cl] (dppp=1,3-Bis(diphenylphosphino)propane) enables the alkylation of a large variety of tertiary allyl carbonates with high yields and excellent regioselectivity for the branched product.

Visible-light-induced coupling of carboxylic acids with alcohols/amines via a phosphorous linchpin strategy.

The combination of activated carboxylic acids and alcohols/amines to access esters and amides, respectively, is a cornerstone of organic chemistry and has been well developed over the past century. These dehydrations are extensively used in medicinal chemistry and natural product synthesis due to the prevalence of these functional groups in bioactive molecules. Here, we report a divergent process from the expected ester/amide outcomes through a light-induced coupling of activated carboxylic acids and alcohols/amines to efficiently prepare α-hydroxy/amino ketones or β-ketophosphonates via single-electron chemistry.

Insight into Radical Initiation, Solvent Effects, and Biphenyl Production in Iron-Bisphosphine Cross-Couplings.

Iron-bisphosphines have attracted broad interest as highly effective and versatile catalytic systems for two- and three-component cross-coupling strategies. While recent mechanistic studies have defined the role of organoiron(II)-bisphosphine species as key intermediates for selective cross-coupled product formation in these systems, mechanistic features that are essential for catalytic performance remain undefined. Specifically, key questions include the following: what is the generality of iron(II) intermediates for radical initiation in cross-couplings? What factors control reactivity toward homocoupled biaryl side-products in these systems? Finally, what are the solvent effects in these reactions that enable high catalytic performance? Herein, we address these key questions by examining the mechanism of enantioselective coupling between α-chloro- and α-bromoalkanoates and aryl Grignard reagents catalyzed by chiral bisphosphine-iron complexes.