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Nitrogen-vacancy (NV) centers in diamond are a promising platform for nanoscale NMR sensing. Despite significant progress toward using NV centers to detect and localize nuclear spins down to the single spin level, NV-based spectroscopy of individual, intact, arbitrary target molecules remains elusive. Such sensing requires that target molecules are immobilized within nanometers of NV centers with long spin coherence. The inert nature of diamond typically requires harsh functionalization techniques such as thermal annealing or plasma processing, limiting the scope of functional groups that can be attached to the surface. Solution-phase chemical methods can be readily generalized to install diverse functional groups, but they have not been widely explored for single-crystal diamond surfaces. Moreover, realizing shallow NV centers with long spin coherence times requires highly ordered single-crystal surfaces, and solution-phase functionalization has not yet been shown with such demanding conditions. In this work, we report a versatile strategy to directly functionalize C--H bonds on single-crystal diamond surfaces under ambient conditions using visible light, forming C--F, C--Cl, C--S, and C--N bonds at the surface. This method is compatible with NV centers within 10 nm of the surface with spin coherence times comparable to the state of the art. As a proof-of-principle demonstration, we use shallow ensembles of NV centers to detect nuclear spins from surface-bound functional groups. Our approach to surface functionalization opens the door to deploying NV centers as a tool for chemical sensing and single-molecule spectroscopy. [ABSTRACT FROM AUTHOR]

Quantum mechanics revolutionized chemists' understanding of molecular structure. In contrast, the kinetics of molecular reactions in solution are well described by classical, statistical theories. To reveal how the dynamics of chemical systems transition from quantum to classical, we study femtosecond proton transfer in a symmetric molecule with two identical reactant sites that are spatially apart. With the reaction launched from a superposition of two local basis states, we hypothesize that the ensuing motions of the electrons and nuclei will proceed, conceptually, in lockstep as a superposition of probability amplitudes until decoherence collapses the system to a product. Using ultrafast spectroscopy, we observe that the initial superposition state affects the reaction kinetics by an interference mechanism. With the aid of a quantum dynamics model, we propose how the evolution of nuclear wavepackets manifests the unusual intersite quantum correlations during the reaction. [ABSTRACT FROM AUTHOR]

Author(s): Gilbert J. Choi [1]; Qilei Zhu [1]; David C. Miller [1]; Carol J. Gu [1]; Robert R. Knowles (corresponding author) [1] Despite advances in hydrogen atom transfer (HAT) catalysis [...]

A method is described for the isomerization of acyclic allylic alcohols into β‐functionalized ketones via 1,3‐alkyl transposition. This reaction proceeds via light‐driven proton‐coupled electron transfer (PCET) activation of the O−H bond in the allylic alcohol substrate, followed by C−C β‐scission of the resulting alkoxy radical. The transient alkyl radical and enone acceptor generated in the scission event subsequently recombine via radical conjugate addition to deliver β‐functionalized ketone products. A variety of allylic alcohol substrates bearing alkyl and acyl migratory groups were successfully accommodated. Insights from mechanistic studies led to a modified reaction protocol that improves reaction performance for challenging substrates. [ABSTRACT FROM AUTHOR]

We report a catalytic, light‐driven method for the intramolecular hydroetherification of unactivated alkenols to furnish cyclic ether products. These reactions occur under visible‐light irradiation in the presence of an IrIII‐based photoredox catalyst, a Brønsted base catalyst, and a hydrogen‐atom transfer (HAT) co‐catalyst. Reactive alkoxy radicals are proposed as key intermediates, generated by direct homolytic activation of alcohol O−H bonds through a proton‐coupled electron‐transfer mechanism. This method exhibits a broad substrate scope and high functional‐group tolerance, and it accommodates a diverse range of alkene substitution patterns. Results demonstrating the extension of this catalytic system to carboetherification reactions are also presented. [ABSTRACT FROM AUTHOR]

The mechanism of aldehyde [alpha]-oxyamination reaction is analyzed and the use of a validated cyclopropane-based radical-clock substrate has shown that carbon-oxygen bond formation has occurred through an enamine activation manifold. The studies have shown that complexation between TEMPO and a simple metal salt has led to electrophilic ionic reactivity.

A new thiourea catalyst is described for the enantioselective cationic polycyclization of hydroxylactams. The studies have provided evidence for a mechanism in which stabilizing cation-[pi] interactions are a principal determinant of enantioselectivity.

Concepts for the thermodynamically challenging synthesis of weak N–H bonds by photoinduced proton coupled electron transfer are explored. Upon irradiation with blue light, ammonia synthesis was achieved from the manganese nitride (tBuSalen)MnN (tBuSalen = (S,S)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine) in the presence of 9,10-dihydroacridine and a ruthenium photocatalyst in iPrOH solution. Although in one case the ruthenium complex bears a remote N–H bond that weakens to 41 kcal mol−1 upon irradiation, control experiments with the N-methylated analog demonstrate the ruthenium complex serves as a photoreductant rather than hydrogen-atom transfer catalyst in aprotic solvents. Luminescence quenching experiments support a ruthenium(ii)/(iii) cycle rather than a ruthenium(i)/(ii) alternative. Identification of the manganese complex following ammonia synthesis was also accomplished. [ABSTRACT FROM AUTHOR]

Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon-hydrogen (C-H) bond functionalization. In the latter process-a subset of the classical Hofmann-Löffler-Freytag reaction-amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Löffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using traditional HAT-based approaches. [ABSTRACT FROM AUTHOR]

Conspectus Redox events in which an electron and proton are exchanged in a concerted elementary step are commonly referred to as proton-coupled electron transfers (PCETs). PCETs are known to operate in numerous important biological redox processes, as well as recent inorganic technologies for small molecule activation. These studies suggest that PCET catalysis might also function as a general mode of substrate activation in organic synthesis. Over the past three years, our group has worked to advance this hypothesis and to demonstrate the synthetic utility of PCET through the development of novel catalytic radical chemistries. The central aim of these efforts has been to demonstrate the ability of PCET to homolytically activate a wide variety of common organic functional groups that are energetically inaccessible using known molecular H atom transfer catalysts. To do so, we made use of a simple formalism first introduced by Mayer and co-workers that allowed us to predict the thermodynamic capacity of any oxidant/base or reductant/acid pair to formally add or remove H· from a given substrate. With this insight, we were able to rationally select catalyst combinations thermodynamically competent to homolyze the extraordinarily strong E-H s-bonds found in many common protic functional groups (BDFEs > 100 kcal/mol) or to form unusually weak bonds to hydrogen via the reductive action of common organic p-systems (BDFEs < 35 kcal/mol). These ideas were reduced to practice through the development of new catalyst systems for reductive PCET activations of ketones and oxidative PCET activation of amide N-H bonds to directly furnish reactive ketyl and amidyl radicals, respectively. In both systems, the reaction outcomes were found to be successfully predicted using the effective bond strength formalism, suggesting that these simple thermochemical considerations can provide useful and actionable insights into PCET reaction design. The ability of PCET catalysis to control enantioselectivity in free radical processes has also been established. Specifically, multisite PCET requires the formation of a pre-equilibrium hydrogen bond between the substrate and a proton donor/acceptor prior to charge transfer. We recognized that these H-bond interfaces persist following the PCET event, resulting in the formation of noncovalent complexes of the nascent radical intermediates. When chiral proton donors/acceptors are employed, this association can provide a basis for asymmetric induction in subsequent bond-forming steps. We discuss our efforts to capitalize on this understanding via the development of a catalytic protocol for enantioselective aza-pinacol cyclizations. Lastly, we highlight an alternative PCET mechanism that exploits the ability of redox-active metals to homolytically weaken the bonds in coordinated ligands, enabling nominally strong bonds (BDFEs ~ 100 kcal) to be abstracted by weak H atom acceptors with concomitant oxidation of the metal center. This "soft homolysis" mechanism enables the generation of metalated intermediates from protic substrates under completely neutral conditions. The first example of this form of catalysis is presented in the context of a catalytic C-N bond forming reaction jointly mediated by bulky titanocene complexes and the stable nitroxyl radical TEMPO. [ABSTRACT FROM AUTHOR]

A new catalytic method is described to access carbocation intermediates via the mesolytic cleavage of alkoxyamine radical cations. In this process, electron transfer between an excited state oxidant and a TEMPO-derived alkoxyamine substrate gives rise to a radical cation with a remarkably weak C−O bond. Spontaneous scission results in the formation of the stable nitroxyl radical TEMPO. as well as a reactive carbocation intermediate that can be intercepted by a wide range of nucleophiles. Notably, this process occurs under neutral conditions and at comparatively mild potentials, enabling catalytic cation generation in the presence of both acid sensitive and easily oxidized nucleophilic partners. [ABSTRACT FROM AUTHOR]

Here we describe a dual catalyst system comprised of an iridium photocatalyst and weak phosphate base that is capable of both selectively homolyzing the N-H bonds of N-arylamides (bond dissociation free energies ~ 100 kcal/mol) via concerted proton-coupled electron transfer (PCET) and mediating efficient carboamination reactions of the resulting amidyl radicals. This manner of PCET activation, which finds its basis in numerous biological redox processes, enables the formal homolysis of a stronger amide N-H bond in the presence of weaker allylic C-H bonds, a selectivity that is uncommon in conventional molecular H atom acceptors. Moreover, this transformation affords access to a broad range of structurally complex heterocycles from simple amide starting materials. The design, synthetic scope, and mechanistic evaluation of the PCET process are described. [ABSTRACT FROM AUTHOR]