Electrophilic Cyanation Research Articles

Enantioselective electrophilic cyanation of β-keto amides catalysed by a cinchona organocatalyst

An operationally simple protocol for the enantioselective electrophilic α-cyanation of β-keto amides catalyzed by cinchona-derived catalysts has been demonstrated. The resulting products could be obtained with good to high enantioselectivities (up to 88% ee) and with excellent yields (up to 94%) by employing the mild active 4-acetylphenyl cyanate as the cationic cyano source in the catalytic asymmetric α-cyanation reaction.

Electrophilic Cyanation of Boron Enolates: Efficient Access to Various β‐Ketonitrile Derivatives

AbstractThe highly efficient electrophilic cyanation of boron enolates using readily available cyanating reagents, N‐cyano‐N‐phenyl‐p‐toluenesulfonamide (NCTS) and p‐toluenesulfonyl cyanide (TsCN), is reported. Various β‐ketonitriles were prepared by this new protocol, which has a remarkably broad substrate scope compared to existing methods. The present method also allowed efficient synthesis of β‐ketonitriles containing a quaternary α‐carbon center. In addition, a preliminary result with the use of a chiral boron enolate for the enantioselective cyanation reaction is described.

Electrophilic Cyanation of Boron Enolates: Efficient Access to Various β-Ketonitrile Derivatives.

The highly efficient electrophilic cyanation of boron enolates using readily available cyanating reagents, N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) and p-toluenesulfonyl cyanide (TsCN), is reported. Various β-ketonitriles were prepared by this new protocol, which has a remarkably broad substrate scope compared to existing methods. The present method also allowed efficient synthesis of β-ketonitriles containing a quaternary α-carbon center. In addition, a preliminary result with the use of a chiral boron enolate for the enantioselective cyanation reaction is described.

The application of NCTS (N-cyano-N-phenyl-p-toluenesulfonamide) in palladium-catalyzed cyanation of arenediazonium tetrafluoroborates and aryl halides

Using NCTS (N-cyano-N-phenyl-p-toluenesulfonamide) as an electrophilic cyanation reagent, palladium-catalyzed cyanation of arenediazonium tetrafluoroborates and aryl halides was achieved under mild conditions. The method allowed the effective synthesis of various aryl nitriles in suitable yields via a coupling reaction.

ChemInform Abstract: Organic Base‐Promoted Enantioselective Electrophilic Cyanation of β‐Keto Esters by Using Chiral Phase‐Transfer Catalysts.

AbstractHighly enantioselective cyanation of β‐keto esters such as (I), (IV), and (VI) is achieved using hypervalent iodine reagent (II) as electrophilic cyanating reagent and a cinchona alkaloid‐based chiral quaternary ammonium salt as catalyst.

ChemInform Abstract: Copper‐Catalyzed Aerobic Radical C—C Bond Cleavage of N—H Ketimines.

AbstractThe title process is applied for the synthesis of oxaspirocyclohexadienones as well as in the electrophilic cyanation of Grignard reagents.

Rhodium-Catalyzed Transnitrilation of Aryl Boronic Acids with Dimethylmalononitrile.

An efficient transnitrilation of aryl boronic acids with dimethylmalononitrile (DMMN) is described. This rhodium-catalyzed electrophilic cyanation presents a novel approach to prepare aryl nitriles by using a carbon-bound cyanating reagent which undergoes cross-coupling with the aryl boronic acid. The reaction expands the degree of functional-group compatibility exhibited by the transnitrilation of aryl Grignard and aryllithium reagents. A variety of aryl boronic acid derivatives and dialkylmalononitriles were amenable to the transnitrilation.

Rhodium‐Catalyzed Transnitrilation of Aryl Boronic Acids with Dimethylmalononitrile

AbstractAn efficient transnitrilation of aryl boronic acids with dimethylmalononitrile (DMMN) is described. This rhodium‐catalyzed electrophilic cyanation presents a novel approach to prepare aryl nitriles by using a carbon‐bound cyanating reagent which undergoes cross‐coupling with the aryl boronic acid. The reaction expands the degree of functional‐group compatibility exhibited by the transnitrilation of aryl Grignard and aryllithium reagents. A variety of aryl boronic acid derivatives and dialkylmalononitriles were amenable to the transnitrilation.

Copper-catalyzed aerobic radical C-C bond cleavage of N-H ketimines.

We report herein studies on copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines. Treatment of N–H ketimines having an α-sp3 hybridized carbon under Cu-catalyzed aerobic reaction conditions resulted in a radical fragmentation with C–C bond cleavage to give the corresponding carbonitrile and carbon radical intermediate. This radical process has been applied for the construction of oxaspirocyclohexadienones as well as in the electrophilic cyanation of Grignard reagents with pivalonitrile as a CN source.

ChemInform Abstract: A Facile Synthesis of 2‐Aminobenzoxazoles and 2‐Aminobenzimidazoles Using N‐Cyano‐N‐phenyl‐p‐toluenesulfonamide (NCTS) as an Efficient Electrophilic Cyanating Agent.

AbstractThe newly developed protocol delivers 2‐aminobenzoxazoles in high yields and 2‐aminobenzimidazoles in moderate yields.

Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis.

An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C-H cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct.

Dihalo(imidazolium)sulfuranes: A Versatile Platform for the Synthesis of New Electrophilic Group-Transfer Reagents.

The syntheses of imidazolium thiocyanates and imidazolium thioalkynes from dihalo(imidazolium) sulfuranes are reported and their reactivities as CN(+) and R-CC(+) synthons evaluated, respectively. The easy and scalable preparation of these electrophilic reagents, their operationally simple handling, broad substrate scope, and functional group tolerance clearly illustrate the potential of these species to become a reference for the direct electrophilic cyanation and alkynylation of organic substrates.

ChemInform Abstract: The Direct Electrophilic Cyanation of β‐Keto Esters and Amides with Cyano Benziodoxole.

AbstractThe developed method is applicable to cyclic β‐ketoesters, but not to acyclic ones.

Mechanism and Origins of Selectivities in the Copper-Catalyzed Dearomatization-Induced ortho C–H Cyanation of Vinylarenes

The mechanism of the copper-catalyzed regioselective ortho C–H cyanation of vinylarenes has been investigated using density functional theory calculations. This C–H cyanation is composed of two discrete catalytic cycles (the copper-catalyzed electrophilic cyanative dearomatization and the subsequent base-catalyzed hydrogen transposition) that furnish the ortho C–H cyanated arenes. The electrophilic cyanation step features a unique six-membered transition state, leading to the formation of the dearomatized intermediate with a high level of site selectivity. Such dearomatization significantly increases the reactivity of the C–H bond, thereby enabling the base-assisted C–H activation in the following steps.

A Facile Synthesis of 2-Aminobenzoxazoles and 2-Aminobenzimidazoles Using N-Cyano-N-phenyl-p-toluenesulfonamide (NCTS) as an Efficient Electrophilic Cyanating Agent

A facile synthesis of 2-aminobenzoxazole and 2-aminobenz­imidazole derivatives employing a nonhazardous electrophilic cyanating agent: <i>N</i>-cyano-<i>N</i>-phenyl-<i>p</i>-toluenesulfonamide (NCTS) with various substituted 2-aminophenols and benzene-1,2-diamine derivatives in the presence of lithium hexamethyldisilazide (LiHMDS) is described. This novel protocol boasts operational simplicity, shorter reaction time, and simple workup.

Organic base-promoted enantioselective electrophilic cyanation of β-keto esters by using chiral phase-transfer catalysts.

Highly enantioselective cyanation of β-keto esters using hypervalent iodine(iii) as the electrophilic cyanating reagent induced by cinchona alkaloid-based chiral quaternary ammonium salt was demonstrated. Organic bases, especially DMAP, in the chiral phase-transfer catalysis were used to obtain high ees.

The direct electrophilic cyanation of β-keto esters and amides with cyano benziodoxole.

The direct electrophilic α-cyanation of β-keto esters and amides has been developed using a hypervalent iodine benziodoxole-derived cyano reagent. The procedure is accomplished within 10 min and without the use of any catalyst in DMF, at room temperature. Thus, the highly functionalized quaternary carbon-centered nitriles were produced in high to excellent yields.

ChemInform Abstract: A Simple Method for the Electrophilic Cyanation of Secondary Amines.

Bleach oxidizes trimethylsilyl cyanide to generate an electrophilic cyanating reagent that readily reacts with an amine nucleophile. This oxidative N-cyanation reaction allows for the preparation of disubstituted cyanamides from amines without using highly toxic cyanogen halides.

A simple method for the electrophilic cyanation of secondary amines.

Bleach oxidizes trimethylsilyl cyanide to generate an electrophilic cyanating reagent that readily reacts with an amine nucleophile. This oxidative N-cyanation reaction allows for the preparation of disubstituted cyanamides from amines without using highly toxic cyanogen halides.

ChemInform Abstract: Practical Synthesis of Aromatic Nitriles via Gallium‐Catalyzed Electrophilic Cyanation of Aromatic C—H Bonds.

AbstractThe cyanation of heteroarenes (I) and arenes (IV) proceeds with very high regioselectivity to afford single products (III) and (V), whilst the reaction of biaryl (VI) affords a mixture of isomers (VII) and (VIII).