Alkyne and Reversible Nitrile Activation: N,N '-Diamidocarbene-Facilitated Synthesis of Cyclopropenes, Cyclopropenones, and Azirines

We report the synthesis of a variety of diamidocyclopropenes by combining an isolable and readily accessible N,N'-diamidocarbene (DAC) with a range of alkynes (nine examples, 68-97% yield). Subsequent hydrolysis of selected cyclopropenes afforded the corresponding cyclopropenones or alpha,beta-unsaturated acids, depending on the reaction conditions. In addition, the combination of a DAC with alkyl or aryl nitriles was found to form 2H-azirines in a reversible manner (four examples, K-eq = 4-72 M-1 at 30 degrees C in toluene)

Reductive generation of stable, five-membered N,N '-diamidocarbenes

The synthesis of the first stable, five-membered N,N'-diamidocarbenes (DACs), including a differentially N-substituted derivative, was achieved via the reduction of a geminal dichloride precursor using potassium. Key differences between the reactivity of the five-membered DACs and their six-membered congeners were observed, including an ability to insert into electron-rich C-H bonds

Dihaloimidazolidinediones as Versatile Halodehydrating Agents

Dihaloimidazolidinediones containing geminal dibromides, dichlorides, or diiodides were synthesized and used to transform various alcohols to their corresponding alkyl halides in high yields and under mild conditions. High functional group tolerance and, in many cases, high selectivities were observed. Efforts toward elucidating the mechanism revealed that significant charge build-up may occur at the eventual halogen containing carbon nucleus prior to substitution.close

Olefin Metathesis Catalysts Containing N,N '-Diamidocarbenes

A series of Ru-based olefin metathesis catalysts containing N,N'-diamidocarbenes (DACs) were synthesized and studied. X-ray crystallographic analysis revealed that the Ru-C-carbene distances (1.938(5)-1.984(4) angstrom) measured in the DAC-supported complexes were relatively short, particularly in comparison to the range of Ru-C-carbene sdistances typically observed in analogous N-heterocyclic carbene (NHC) supported complexes (1.96-2.03 angstrom). While the Tolman electronic parameters (TEP) of various DACs (2056-2057 cm(-1)) were calculated to be similar to that of PCy3 (2056 cm(-1)), the ring-closing metathesis (RCM) of diethyl diallylmalonate facilitated by DAC-supported Ru complexes proceeded at a relatively slow rate. However, unlike the phosphine-containing complexes, the DAC analogues catalyzed the RCM of diethyl dimethallylmalonate to its respective tetrasubstituted olefin. A series of electrochemical experiments revealed that the Ru complexes bearing a DAC ligand underwent oxidation at significantly higher potentials (Delta E-pa > 0.5 V) than analogous complexes containing phosphines and various N-heterocyclic carbenes (NHCs), including a tetrahydropyrimidinylidene, a saturated and strongly donating NHC analogue of the DAC. The relative catalytic activities observed were attributed to the steric properties of the aforementioned ligands

N,N'-Diamidocarbenes: Isolable Divalent Carbons with Bona Fide Carbene Reactivity

Since the first reported isolation of a carbene just over a quarter century ago, the study of such compounds including stable derivatives has flourished. Indeed, N-heterocyclic carbenes (NHCs), of which imidazolylidenes and their derivatives are the most pervasive subclass, feature prominently in organocatalysis, as ligands for transition metal catalysts, and as stabilizers of reactive species. However, imidazolylidenes (and many other NHCs) typically lack the reactivity characteristic of electrophilic carbenes, including insertion into unactivated C-H bonds, participation in [2 + 1] cycloadditions, and reaction with carbon mohoxide. This has led to debates over whether NHCs are truly carbenic in nature or perhaps better regarded as ylides. The fundamental and synthetic utility of transformations that involve electrophilic carbenes has motivated our group and others to expand the reactivity of NHCs and other stable carbenes to encompass electrophilic carbene chemistry. These efforts have led to the develophient of the diamidocarbenes (DAcs), a stable and unique subset of the NHCs that feature carbonyl groups inserted into the N-heterocyclic scaffold. To date, crystalline five-, six-, and seven-membered DACs have been prepared and studied. Unlike imidaiolylidenes, which are often designated as prototypical NHCs, the DACs "exhibit a reactivity profile similar to that of bona fide carbenes, reactive species that are less "tamed" by heteroatom Pi conjugation. The DACs engage in [2 + 1] cycloadditions with electron-rich or -poor alkenes, aldehydes, alkynes, and nitriles, and doing so "in a reversible manner in some cases. They also react with isonitriles, reversibly couple to CO, and mediate the dehydrogenation of hydrocarbons. Such rich chemistry may be rationalized in terms of their ambiphilicity: DACs are nucleophilic, as required for some of the reactions above, yet also have electrophilic character, as evidenced by their insertions into unactivated N-H and CH bonds, including nonacidic derivatives. As will become clear, such reactivity is unique among isolable carbenes. DAC chemistry is expected to find applications in synthesis, dynamic covalent chemistry, and catalysis: For example, the hydrolysis of DAC-derived diamidocyclopropanes and -propenes affords carboxylic acids and cyclopropenones, respectively. These new hydrocarboxylation and carbonylation methodologies are significant in that they represent alternatives to processes that typically involve precious metals and gaseous carbon monoxide. Future efforts in this area may involve modifications that transform the stoichiometric conversions facilitated by DACs into catalytic variants. In this context, the reversible binding of CO to DACs is an indication that the latter. ay serve as a blueprint for the development of more electrophilic, stable carbenes with the capacity to activate other challenging small molecules. © 2016 American Chemical Society126261sciescopu

N,N'-Diamidocarbenes: Isolable Divalent Carbons with Bona Fide Carbene Reactivity

Since the first reported isolation of a carbene just over a quarter century ago, the study of such compounds including stable derivatives has flourished. Indeed, N-heterocyclic carbenes (NHCs), of which imidazolylidenes and their derivatives are the most pervasive subclass, feature prominently in organocatalysis, as ligands for transition metal catalysts, and as stabilizers of reactive species. However, imidazolylidenes (and many other NHCs) typically lack the reactivity characteristic of electrophilic carbenes, including insertion into unactivated C-H bonds, participation in [2 + 1] cycloadditions, and reaction with carbon mohoxide. This has led to debates over whether NHCs are truly carbenic in nature or perhaps better regarded as ylides. The fundamental and synthetic utility of transformations that involve electrophilic carbenes has motivated our group and others to expand the reactivity of NHCs and other stable carbenes to encompass electrophilic carbene chemistry. These efforts have led to the develophient of the diamidocarbenes (DAcs), a stable and unique subset of the NHCs that feature carbonyl groups inserted into the N-heterocyclic scaffold. To date, crystalline five-, six-, and seven-membered DACs have been prepared and studied. Unlike imidaiolylidenes, which are often designated as prototypical NHCs, the DACs "exhibit a reactivity profile similar to that of bona fide carbenes, reactive species that are less "tamed" by heteroatom Pi conjugation. The DACs engage in [2 + 1] cycloadditions with electron-rich or -poor alkenes, aldehydes, alkynes, and nitriles, and doing so "in a reversible manner in some cases. They also react with isonitriles, reversibly couple to CO, and mediate the dehydrogenation of hydrocarbons. Such rich chemistry may be rationalized in terms of their ambiphilicity: DACs are nucleophilic, as required for some of the reactions above, yet also have electrophilic character, as evidenced by their insertions into unactivated N-H and CH bonds, including nonacidic derivatives. As will become clear, such reactivity is unique among isolable carbenes. DAC chemistry is expected to find applications in synthesis, dynamic covalent chemistry, and catalysis: For example, the hydrolysis of DAC-derived diamidocyclopropanes and -propenes affords carboxylic acids and cyclopropenones, respectively. These new hydrocarboxylation and carbonylation methodologies are significant in that they represent alternatives to processes that typically involve precious metals and gaseous carbon monoxide. Future efforts in this area may involve modifications that transform the stoichiometric conversions facilitated by DACs into catalytic variants. In this context, the reversible binding of CO to DACs is an indication that the latter. ay serve as a blueprint for the development of more electrophilic, stable carbenes with the capacity to activate other challenging small molecules.ope

Exploring the Chemistry of N,N '-Diamidocarbenes with Organophosphorus Compounds

A readily available N,N'-diamidocarbene (DAC) was found to insert into the P-H bonds of primary and secondary phosphines as well as a phosphonate ester. In contrast, tertiary phosphines catalyzed the ring contraction of the DAC to an iminopyrrolidinedione. Treating the DAC with trimethyl phosphite afforded the corresponding diamidophosphonate ester and olefinic products expected from an Arbuzov-type reaction

Alkyne and Reversible Nitrile Activation: <i>N</i>,<i>N</i>′-Diamidocarbene-Facilitated Synthesis of Cyclopropenes, Cyclopropenones, and Azirines

We report the synthesis of a variety of diamidocyclopropenes by combining an isolable and readily accessible <i>N</i>,<i>N</i>′-diamidocarbene (DAC) with a range of alkynes (nine examples, 68–97% yield). Subsequent hydrolysis of selected cyclopropenes afforded the corresponding cyclopropenones or α,β-unsaturated acids, depending on the reaction conditions. In addition, the combination of a DAC with alkyl or aryl nitriles was found to form 2<i>H</i>-azirines in a reversible manner (four examples, <i>K</i>_eq = 4–72 M^–1 at 30 °C in toluene)

Ammonia N-H activation by a N,N &apos;-diamidocarbene

The synthesis and characterization of N,N&apos;-dimesityl-4,6-diketo-5,5-dimethylpyrimidin-2-ylidene is reported; this crystalline N,N&apos;-diamidocarbene was found to split ammonia and engage in other reactions not exhibited by typical N-heterocyclic carbenes

Elucidating the Mechanism of Reversible Oxiranations via Magnetization Transfer Spectroscopy

The reversible [2 + 1] cycloadditions between an N,N&apos;-diamidocarbene (DAC) and eight aldehydes were examined using NMR spectroscopy. Variable temperature magnetization transfer experiments revealed higher exchange rates and lower activation barriers when electron-deficient aldehydes were employed. Likewise, competitive equilibrium studies indicated a thermodynamic preference for electron-deficient aryl and sterically unhindered alkyl aldehydes compared to more electron-rich or bulkier substrates. Collectively, these and other data collected were consistent with the oxiranation process proceeding in an asynchronous manner