Α-amino Nitriles Research Articles

Cellulose sulfuric acid as a bio-supported and recyclable solid acid catalyst for the one-pot three-component synthesis of α-amino nitriles

α-Amino nitriles are synthesized by a one-pot three-component condensation reaction of amines, aldehydes and trimethylsilylcyanide in the presence of a catalytic amount of cellulose sulfuric acid as a bio-supported catalyst, in excellent yields with short reaction times at ambient temperature. The reaction work-up is simple and the catalyst can be easily separated from the product and reused in subsequent reactions.

Advantage of in situ generation of N-arylsulfonyl imines from α-amide sulfones in the phase-transfer-catalyzed asymmetric Strecker reaction

Highly efficient, catalytic enantioselective synthesis of N-arylsulfonyl α-amino nitriles from the corresponding α-amido sulfones has been achieved under toluene–aqueous potassium cyanide biphasic conditions using chiral quaternary ammonium iodide ( R, R, R)- 1 as an effective phase-transfer catalyst. This Strecker synthesis involving the in situ generation of the reactive N-sulfonyl imines is advantageous for the cyanation of the substrates having primary and secondary alkyl substituents.

Phase Transfer Catalyzed Enantioselective Strecker Reactions of α-Amido Sulfones with Cyanohydrins

A study into the use of a chiral phase-transfer catalyst in conjunction with acetone cyanohydrin to effect the enantioselective formation of alpha-amino nitriles from alpha-amido sulfones is described. This novel catalytic asymmetric Strecker reaction is analyzed with regard to the possible mechanistic basis.

Lanthanum(III) nitrate hexahydrate or gadolinium(III) chloride hexahydrate catalyzed one-pot synthesis of α-amino nitriles

A simple, convenient and general method has been developed for the synthesis of α-aminonitriles by a one-pot three component condensation of aldehydes, amines and trimethyl silyl cyanide in acetonitrile in the presence of a catalytic amount of La(NO 3) 3·6H 2O or GdCl 3·6H 2O.

H14[NaP5W30O110] as an Efficient Catalyst for the One-Pot Synthesis of α-Amino Nitriles

In this study, the synthesis of some α-amino nitriles is reported. The compounds were prepared by the nucleophilic addition reaction of aldehydes and amines with TMSCN in the presence of a catalytic amount of H 14 [NaP 5 W 30 O 110 ], Preyssler's heteropoly acid, in excellent yields. The catalyst can be recovered and reused in subsequent reactions.

A practical synthesis of 3-ethyl- l-norvaline

An efficient process for the synthesis of 3-ethyl- l-norvaline has been developed. The route makes use of a Strecker reaction, whereby ( S)-(−)-α-methylbenzylamine acts as a chiral auxiliary to provide nearly diastereomerically pure α-amino nitrile. Crystallization-induced asymmetric transformation enhances the yield and diastereomeric ratio and allows for efficient isolation of the product. The amino nitrile intermediate is converted to enantiomerically pure 3-ethyl- l-norvaline in three steps.

Towards Reaction Selectivities of Imines and Aziridines

Several simple and convenient transformations of imines and aziridines under mild conditions have been developed, rendering access to several kinds of β-amino derivatives, α-amino nitriles and phosphonates, aziridines, and conjugated dienes from imines and aziridines under neutral and metal-free conditions very conveniently. High stereoselectivities are realized in most reactions based upon mechanistic considerations.

Aminoboranes as new iminium ion generators in amination reactions

Abstract The utilization of aminoborane derivatives in amination reactions such as Strecker-type aminative cyanation, Mannich-type reaction, and reductive amination is described. Bis(dialkylamino)cyanoboranes and bis(dialkylamino)boron enolates underwent the concurrent transfer of the amino group and either the cyano or the enoxy group from the boron to carbonyl carbon atom in their reaction with aldehydes, leading to the formation of α-amino nitriles and β-amino ketones, respectively. Bis(dialkylamino)borane derivatives that lack the additional nucleophilic groups on the boron atoms were found to serve as effective generators of iminium ions from aldehydes. In the presence of these aminoboranes, reactions of aldehydes with ketene silyl acetals or silyl enol ethers take place, giving Mannich-type products, i.e., β-amino esters and ketones, selectively. Using diisopropylamino-substituted boron compounds, which are designed as "universal" iminium ion generators, reactions of free sec-amines, aldehydes, and ketene silyl acetals proceed efficiently, giving β-amino esters in which the amino groups are derived exclusively from the free amines. The use of the universal iminium ion generator is also effective for reductive amination of aldehydes, in which NaBH4 is used as a hydride donor.

Rapid generation of molecular complexity using “hybrid” multi-component reactions (MCRs): application to the synthesis of α-amino nitriles and 1,2-diamines

Methyleneaziridines can be converted into a wide range of 1,2-diamines and 2-cyanopiperidines in a single operation with the formation of three intermolecular carbon-carbon bonds using a "hybrid" MCR.

Bicyclic glutamic acid derivatives

For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide.

Multicomponent Strecker Reaction under High Pressure.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel Domino Cyclization of Tryptophan-Derived Amino Nitriles: Scope and Stereoselectivity

[reaction: see text] The scope and stereoselectivity of the acid-promoted cyclization of new tryptophan-based alpha-amino nitriles derived from either ketones or aldehydes to novel hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indoles is described. This cyclization involves the generation of two or three stereogenic centers. The time and stereoselectivity of this reaction mostly depended on both the steric volume of the substituents at the amino nitrile and its stereochemistry. Unhindered amino nitriles gave exclusively 2-exo-isomers, while hindered amino nitriles, which required higher reaction times, provided also these isomers under kinetic control. Under thermodynamic control, the 2-endo-isomer was the main reaction product, except for the benzaldehyde-derived alpha-amino nitriles, where a favorable electronic interaction between the phenyl and methoxycarbonyl groups in a relative cis-disposition might be responsible of the formation of the 2-exo-isomer as the only cyclization product.

Molecular Iodine Catalyzed Imine Activation for Three‐Component Nucleophilic Addition Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Molecular Iodine-Catalyzed Imine Activation for Three-Component ­Nucleophilic Addition Reactions

β-Amino ketones and α-amino nitriles were synthesized from silyl enol ethers and trimethylsilyl cyanides, via a three-component nucleophilic addition reaction with aromatic aldehydes and amines; the reaction was found to be significantly accelerated by molecular iodine under neutral conditions.

Reactions of enantiopure ß-ketimino sulfoxides with Et2AlCN. Scope and limitations in asymmetric synthesis of α-amino nitriles

Results obtained in the reactions of Et2AlCN with exocyclic, endocyclic, and acyclic α-p- tolylsulfinyl ketimines are reported. Good conversions and satisfactory stereochemical results are obtained exclusively from cyclic ketimines. Imine-enamine equilibrium accounts for the incomplete conversions and low reactivities observed for acyclic amines. Configurational assignments and mechanistic proposals are based on the conformational analysis of substrates and products.

Molecular Diversity via Amino Acid Derived α-Amino Nitriles: Synthesis of Spirocyclic 2,6-Dioxopiperazine Derivatives

[reaction: see text] Chiral spirocyclic 2,6-dioxopiperazines were synthesized from amino acid derived alpha-quaternary alpha-amino nitriles via H(2)SO(4)-promoted cyano hydration, followed by base-mediated cyclization and N-alkylation. This methodology, requiring the previous preparation of the amino nitrile by a modified Strecker reaction, was applied to Phe, Trp, Pro, Asp, Glu, and Ser derivatives. In the case of the Trp-derived amino nitrile the major product of the treatment with H(2)SO(4) was not the expected carboxamide, but a new tetracyclic indoline derivative containing the novel heterocyclic system hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indole, as a result of a domino tautomerization. The treatment of this indoline derivative with refluxing 1 N HCl led to a Trp-derived 2,6-dioxopiperazine. The 2,6-dioxopiperazine ring opened under the reaction conditions of methyl ester saponification, giving N-(carboxyalkyl)amino acid derivatives. Therefore, the synthesis of 2,6-dioxopiperazines containing free carboxylic acids from the respective methyl esters required transesterification to benzyl esters, followed by hydrogenolysis.

Lewis Base-catalyzed Diastereoselective Strecker-type Reaction between Trimethylsilyl Cyanide and Chiral Sulfinimines

Abstract Lewis base-catalyzed diastereoselective Strecker-type reaction between trimethylsilyl cyanide and chiral sulfinimines derived from commercially available (S)-(+)-p-toluenesulfinamide and aliphatic aldehydes proceeded smoothly by using a catalytic amount of tetra-n-butylammonium acetate in DMF to afford the corresponding α-amino nitriles with (Ss,R)-configurations in good to high yields and diastereoselectivities.

Are Multicomponent Strecker Reactions of Diketones with Diamines under High Pressure Amenable to Heterocyclic Synthesis?

Employing double Strecker strategy, two new heterocyclic compounds, 5,6,11,12-tetrahydro-6,1 l-dimethyldibenzo[b,f][1,4]diazocine-6,11-dicarbonitrile and 1,2,3,4,5,10-hexahydrophenazine-4a,10a-dicarbonitrile, were prepared in one step albeit in low yields. The reaction has proven to be very limited, but such a sterically hindered amine as N-methylaniline underwent Strecker reaction with benzaldehyde and TMSCN to give the corresponding α-amino nitriles.

Solution-Phase Parallel Synthesis of Spirohydantoins

Spirohydantoins are considered privileged structures, making them attractive for the preparation of compound libraries with the potential for diverse biological activity. However, very few modifications of this scaffold have been reported to date. The spirohydantoin template was elaborated into a library of 168 compounds through a two-step solution-phase parallel synthesis starting from various N-substituted piperidinones. The Strecker reaction was employed to generate alpha-amino nitriles from aniline and TMSCN (or KCN). Subsequent reaction of the anilido nitrogen with a diverse set of isocyanates, followed by refluxing under acidic conditions, afforded the title library in high yield and purity.

Trimethylsilylcyanation of N-[3-(2-Furyl)-2-propenylidene]trifluoromethylanilines.

The addition of Me3SiCN to N-[3-(2-furyl)-2-propenylidene]trifluoromethylanilines, differing in the position of the CF3 group in the benzene ring and in the presence or absence of a methyl group in the heterocycle, was studied in the presence of aluminum bromide as catalyst. The direction of the process (1,2-addition in all cases) was determined, and certain other features of the reactions were discovered. A series of the corresponding unsaturated heterocyclic α-amino nitriles were synthesized. The molecular and crystal structures of one of them were determined by X-ray crystallographic analysis.