New N,N-diamine ligands derived from (−)-menthol and their application in the asymmetric transfer hydrogenation

Natural (?)-menthol was applied to construction of mono-N-tosylated-1,2-diamine derivatives. The O-tosylation and elimination of the tosylate of the menthol intermediate led to trans-p-menth-2-ene. The unsaturated menth-2-ene was next transformed into a mixture of N-tosylaziridines, which upon reaction with sodium azide gave four isomeric azides. The reduction of the formed tosylazides on Pd/C gave new chiral mono-N-tosylated-1,2-diamines, which were used as ligands in the asymmetric transfer hydrogenation protocol on aromatic ketones and endocyclic imine.     

Synthesis of chiral vicinal C2 symmetric and unsymmetric bis(sulfonamide) ligands based on trans-1,2-cyclohexanediamine by aminolysis of N-tosylaziridines

The ring opening of N-tosylaziridines with aliphatic amines can be efficiently catalyzed by lithium perchlorate to provide derivatives of the trans-1,2-diamine in high yields. The reaction was used in desymmetrization of several cyclic N-tosylaziridines using chiral amines. Using this strategy, an efficient synthesis of chiral vicinal C₂ symmetric bis(sulfonamide) and unsymmetrical bis(sulfonamide) ligands based on trans-1,2-cyclohexanediamine was developed.     

Reaction of N,N-diarylamidines with 3,4,5,6-tetrachloro-1,2-benzoquinone

A synthesis of 5,11b-dihydro-1H-dibenzo[d,f][1,3]diazepin-1-ones was found in the reaction of nitro-substituted N¹,N²-diarylamidines with 3,4,5,6-tetrachloro-1,2-benzoquinone. In contrast, 6,7,8,9-tetrachlorodibenzodioxins were obtained from reaction of N¹,N²-diphenylpropionamidine and N¹,N²-di-(4-tert-butylphenyl)acetamidine with 3,4,5,6-tetrachloro-1,2-benzoquinone.     

Synthesis and transformations of alkyl N-(1-cyclohex-3-enyl)carbamates prepared from cyclohex-3-ene carboxylic acid via Curtius rearrangement

The Curtius rearrangement of cyclohex-3-ene carboxylic acid using diphenylphosphoryl azide in the presence of triethylamime and ethanol, t-butanol or benzyl alcohol has been described. As a result the synthesis of ethyl, t-butyl or benzyl N-(1-cyclohex-3-enyl)carbamates has been achieved in one pot, in good chemical yield. A series of transformations of benzyl N-(1-cyclohex-3-enyl)carbamate, such as iodination and epoxidation, as well as opening of the corresponding ring epoxide, have been carried out leading to some useful oxygenated cyclohexylamimo building blocks.     

Syntheses and X-ray structures of Cu(II) and Zn(II) complexes of N,N′-dibenzyl-(R,R)-1,2-diaminocyclohexane and application to nitroaldol reaction

Chiral Cu(II) and Zn(II) complexes with N,N′-dibenzyl-(R,R)-1,2-diaminocyclohexane ligands were synthesized and characterized. X-ray crystal structures of these complexes reveal that Cu complex has the distorted square-planar geometry and the Zn one has the nearly tetrahedral pattern. The coordination of metals to the chiral diamine ligand leads to a 5-membered metallaheterocycle of (S,S)-configuration of nitrogen atoms. Their asymmetric catalytic activities to nitroaldol reaction of benzaldehyde and nitromethane were examined. The difference of the geometry around metals leads to the opposite preferential configuration of alcohol products using these chiral complexes as asymmetric catalysts in the presence of triethylamine or diisopropylethylamine.     

An efficient preparation of N-per- (or poly)fluorophenyl pyrroles and N-fluoroalkanesulfonyl pyrroles

Hetero-Diels-Alder reaction of N-sulfinyl per- (or poly)fluoroaniline and N-sulfinylfluoroalkanesulfonyl amine with 1,3-dienes affords the corresponding cycloadduct 3,6-dihydro-1,2-thiazine-1-oxide which is readily converted to N-per- (or poly)fluorophenyl pyrrole and N-fluoroalkanesulfonyl pyrrole under mild reaction conditions in good yields.     

Synthesis of N-Z, N-Fmoc or Boc protected α-hydrazinoacids and study of the coupling reaction in solution of N-Z-α-hydrazinoesters

The preparation of chiral orthogonally protected N^α-Z, N^β-Fmoc- or Boc-α-hydrazinoacids derivatives, directly suitable for SPPS, is described in six steps with good yields starting from the corresponding α-aminoacids. The coupling reaction assays performed in liquid phase between N^α-Z-hydrazinoesters and N-Fmoc-α-aminoacids demonstrated the low reactivity of the hydrazinoester derivatives. However, we found that the acid fluoride method allowed the formation of hydrazinodipeptides almost quantitatively.     

Chiral N-phosphonyl imine chemistry: asymmetric 1,2-additions of allylmagnesium bromides

Chiral N-phosphonyl homoallylic amines were synthesized by the reaction of allylmagnesium bromide with chiral N-phosphonyl imines. The C₂-symmetric chiral N-phosphonyl group was optimized for this reaction. Excellent yields and good diastereoselectivities were obtained for eight examples.     

Organocatalyzed stereoselective construction of N-formylpiperidines via a Michael-aza-Henry-hemiaminalization reaction cascade

An efficient asymmetric synthesis of N-formylpiperidines via an organocatalytic Michael-aza-Henry-hemiaminalization reaction cascade of an aldehyde, a nitroalkene, and an N-arylideneformamide is reported. The reaction is triggered by diphenylprolinol trimethylsilyl ether and creates two C-C and one C-N bonds leading to the formation of highly enantio-enriched N-formylpiperidines with five contiguous chiral centers in a one-pot operation.     

One-pot and microwave-assisted synthesis of N-sulfonylaziridines

A novel and efficient microwave-assisted one-step reaction was developed to synthesize chiral N-sulfonylaziridines by the reaction of different chiral amino alcohols and sulfonic chlorides. The newly developed microwave synthetic method has the advantage of reducing the reaction time from 24 to 0.5 h with improved yields (84-93%) and minimizing by-products.     

Synthesis of N-(iodophenyl)-amides via an unprecedented Ullmann-Finkelstein tandem reaction

Using a new Ullmann-Finkelstein tandem reaction, N-(iodophenyl)-amides were synthesized from the corresponding amides and iodo-bromobenzenes. The catalyst/ligand couple CuI/N,N′-dimethyl-cyclohexane-1,2-diamine was used for this reaction in dioxane with K₃PO₄ as base.     

N-Polyfluoroethyl and N-2-chlorodifluorovinyl derivatives of azoles

Reactions of tetrafluoroethylene, chlorotrifluoroethylene and 1,2-dichlorodifluoroethylene with N-potassium salts of imidazole, 2-methylbenzimidazole, 3,5-dimethylpyrazole, 1,2,4-triazole, and benzotriazole lead to the formation of the corresponding N-(1,1,2,2-tetrafluoroethyl), N-(2-chloro-1,1,2-trifluoroethyl), and N-(2-chloro-1,2-difluorovinyl) azoles. Treatment of N-(2-chloro-1,2-difluorovinyl) and N-(2-chloro-1,1,2-trifluoroethyl) derivatives of azoles with tetramethylammonium fluoride is a useful synthetic method for the preparation of heterocycles with 1,2,2,2-tetrafluoroethyl group attached to nitrogen.     

N-Cyanomethyl-β-chloroamines: a convenient source of aziridinium ions

N-Cyanomethyl-β-chloroamines smoothly react with a range of alcohols or amines to give regio- and stereoselectively 1,2-aminoethers or 1,2-diamines. The reaction proceeds through the formation of an intermediate aziridinium ion. The N-cyanomethyl group can then be cleaved easily.     

Asymmetric addition of trimethylsilylcyanide to N-benzylimines catalyzed by recyclable chiral dimeric V(V) salen complex

Chiral dimeric vanadium (V) salen complex (10 mol%) derived from 5,5-Methylene di-[(S,S)-{N-(3-tert-butyl salicylidine)-N′-(3′,5′-di-tert-butyl salicylidene)]-1,2-cyclohexanediamine] with vanadyl suphate followed by auto oxidation was used as efficient catalyst for enantioselective Strecker reaction of N-benzylimines with TMSCN at −30 °C. Excellent yield (92%) of α-aminonitrile and high chiral induction was achieved (ee up to 94%) in case of 2-methoxy substituted N-benzylimines in 10 h. The catalytic system worked well up to four cycles with retention of enantioselectivity.     

An effective synthesis of N,N-dimethylamides from carboxylic acids and a new route from N,N-dimethylamides to 1,2-diaryl-1,2-diketones

Carboxylic acids were heated at 150 °C in DMF in the presence of 1.25 equiv of thionyl chloride to give corresponding N,N-dimethylamides in good yields. Tandem chlorination and amidation reactions occurred in the one-pot procedure. Dicarboxylic acids needed prolonged reaction time to produce bisamides in good yields. Some benzamides were efficiently converted into corresponding 1,2-diaryl-1,2-diketones (benzils) under acyloin condensation conditions in the presence of 4,4′-di-tert-butylbiphenyl (DBB) in THF. Ultrasonic irradiation effectively accelerates the reaction, but it is not critical. However, the presence of DBB is fatal to the reaction. Although a few synthetic methods for benzils from benzoic acids have been reported so far, this method is one of the most convenient and highly reproducible procedures.     

Efficient nitrogen transfer from aldehyde-derived N-acyloxaziridines

The effect of solvent polarity on the reaction of 3-aryl-N-carboxamido- and 3-aryl-N-alkoxycarbonyl oxaziridines has been studied and an efficient procedure for high yielding sulfimidation developed by use of polar solvents. The first examples of asymmetric sulfimidation using novel chiral oxaziridines have been carried out with low diastereoselectivity (up to 30% de).     

N,N′-Dioxide-scandium(III) complex catalyzed highly enantioselective Friedel-Crafts alkylation of indole to alkylidene malonates

A highly efficient enantioselective Friedel-Crafts alkylation of indoles with alkylidene malonates has been developed using chiral N,N′-dioxide L4-scandium(III) complex as the catalyst, giving the corresponding products in high yields with excellent enantioselectivities (up to 99% yield and 95% ee). The product 3a was facilely converted into several interesting compounds, such as tryptamines, indolepropionic acids and β-carbolines. It is noteworthy that the seven-membered β-carboline-like compound has been synthesized for the first time. Based on the crystal structure of the chiral N,N′-dioxide L10-scandium(III) complex, the proposed transition state and possible catalytic cycle were presented to elucidate the reaction mechanism.     

A quantum chemical study on the mechanism of chiral N-oxides-catalyzed Strecker reaction

The mechanism for the Strecker reaction of silyl cyanide (H₃SiCN) and benzaldehyde N-methylimine (PhCHNCH₃) catalyzed by chiral 3,3′-dimethyl-2,2′-bipyridine N,N′-dioxide was investigated using the density functional theory (DFT) at the B3LYP/6-31G* level. The calculations revealed that the non-catalyzed reaction proceeded in a concerted way via a five-membered ring transition state, while the catalytic one occurred stepwisely via a hexacoordinate hypervalent silicate intermediate. It was predicted that both non-catalyzed and catalytic Strecker reactions involved two competitive reaction pathways, that is, addition followed by isomerization or isomerization followed by addition. The calculations indicated that two reaction pathways were comparable for both non-catalyzed and catalytic Strecker reactions. In the catalytic reaction, the strong electron donor (N-O) of chiral N-oxide played an important role in enhancing the reactivity and nucleophilicity of H₃SiCN by coordinating O atom to the Si atom of H₃SiCN. Chiral N-oxide could be used as a good catalyst for the reaction, which was in agreement with the experimental observations.     

Pd catalyzed coupling of 1,2-dibromoarenes and anilines: formation of N,N-diaryl-o-phenylenediamines

1,2-Dibromoarenes were coupled with aniline derivatives to yield N,N-diaryl-o-phenylenediamines in moderate to good yield using a palladium/phosphine or palladium/carbene catalyst system. Under similar conditions, 1,2,4,5-tetrabromobenzene was coupled with aniline derivatives to produce the corresponding tetrasubstituted derivatives which are oxidized on workup to yield azophenines. The sequential reaction of two different anilines with 1-chloro-2-iodobenzene afforded mixed N,N-diaryl-o-phenylenediamines.     

Chiral N-phosphonyl imine chemistry: new reagents and their applications for asymmetric reactions

Novel chiral N-phosphonyl imines 2 have been designed and synthesized using chiral N-phosphoramide 1. These N-phosphonyl imines have been successfully utilized for asymmetric aza-Darzens reaction and asymmetric aza-Henry reaction. The C₂-symmetric chiral auxiliary tolerates oxidation, is not sensitive to racemization and can be recycled for large scale synthesis.