Synthesis of New Chiral Secondary 1,2-Diamines Based on Levopimaric Acid and Their Use as Ligands in Copper(II)-Catalyzed Asymmetric Henry Reaction

Russian Journal of Organic Chemistry - Methods have been developed for the synthesis of new chiral imino amines and unsymmetrically substituted trans-1,2-diamines based on fumaropimaric acid. The...     

Catalytic dissymmetrization of meso-2-imidazolidinones: alternative route to chiral synthons for 1,2-diamines

The chiral functionalization of a simple heterocycle, 1,3-dihydro-2-imidazolone, was achieved by the highly enantioselective monodeacylation of meso-1,3-diacetyl-2-imidazolidinones via an oxazaborolidine-catalyzed borane reduction. This kinetically controlled dissymmetrization is sufficiently effective to provide a synthetic route to either enantiomer of (4S, 5S)- or (4R, 5R)-4,5-dimethoxy-2-imidazolidinone derivatives, which serve as chiral synthons for threo-1,2-diamines.     

An efficient synthesis of chiral terminal 1,2-diamines using an enantiomerically pure [1-(1′R)-methylbenzyl]aziridine-2-yl]methanol

Enantiomerically pure terminal 1,2-diamines, which can serve as precursors for the synthesis of many biologically important compounds, were synthesized efficiently from a commercially available chiral [1-(1′R)-methylbenzyl]aziridine-2-yl]methanol. Various enantiomerically pure 2-vinylaziridines were prepared by Wittig reactions from aziridine-2-carboxaldehyde and the corresponding phosphonium salts. The C(2)-N bond of the vinyl substituted aziridine ring was regioselectively cleaved by azidotrimethylsilane (TMSN₃). The azido group and the double bond were reduced successively to give the target compounds in high yields.     

Mild synthesis of enantiomerically pure imidazo-[1,2-a]azepines mediated by Yb(OTf)3

The reaction of various chiral 2,2′-diaryldialdehydes with achiral and chiral 1,2-diamines in the presence of Lewis acids to give imidazo[1,2-a]azepines was investigated. Best results were achieved with Yb(OTf)₃; the reaction outcome is strongly dependent upon the geometric features of both reactants. Kinetic resolution of rac-2,2′-dinaphthyldialdehyde with (R,R)-1,2-diphenyl-1,2-diamminoethane (up to 92% e.e.) was achieved.     

Synthesis of 1,4-diazines by ring expansion of 1,3-diazines

Fully saturated piperazin-3-one and quinoxalin-3-one derivatives were prepared by reactions of 2-anilino-2-ethoxy-3-oxothiobutanoic acid anilide with aliphatic 1,2-diamines. An unusual ring expansion of the intermediate 1,3-diazines leads to 1,4-diazines. Moreover, quinoxalin-3-one derivatives from chiral trans-1,2-diaminocyclohexane were obtained with diastereoselectivity >95%.     

New chiral zinc complexes: synthesis, structure, and induction of axial chirality

We describe an efficient methodology for the preparation of new chiral zinc complexes by assembling dynamically racemic biphenol derivatives and chiral 1,2-diamines with suitable zinc(II) precursors. Mononuclear and dinuclear zinc(II) complexes were formed from differently substituted biphenols. The solid-state and solution structural characterization of the resulting compounds allowed us to demonstrate a preferential sense of induced axial chirality for mononuclear complexes, a phenomenon that was not observed for the dinuclear ones.     

Straightforward access to pyrazines, piperazinones, and quinoxalines by reactions of 1,2-diaza-1,3-butadienes with 1,2-diamines under solution, solvent-free, or solid-phase conditions

The preparation of tetrahydropyrazines, dihydropyrazines, pyrazines, piperazinones, and quinoxalines by 1,4-addition of 1,2-diamines to 1,2-diaza-1,3-butadienes bearing carboxylate, carboxamide, or phosphorylated groups at the terminal carbon and subsequent internal heterocyclization is described. The solvent-free reaction of carboxylated 1,2-diaza-1,3-butadienes with the same reagents affords piperazinones, while phosphorylated 1,2-diaza-1,3-butadienes yield phosphorylated pyrazines. The solid-phase reaction of polymer-bound 1,2-diaza-1,3-butadienes with 1,2-diamines produces pyrazines.     

The surprising nucleophilic addition of aminochlorocarbenes to diethyl acetylenedicarboxylate and to oxalyl chloride: quinolines and benzo[1,4]diazepines from N-alkylformanilides and oxalyl chloride in the presence of Hünig's base

Vilsmeier reagents derived from N-methylformanilides undergo ready deprotonation with Hünig's base. In xylene, the derived nucleophilic arylaminochlorocarbenes bearing 4-methyl- and 4-methoxy-substituents react with acetylenedicarboxylates to give 2-(2-chloro-1,2-bis(ethoxycarbonyl)vinyl)-3,4-bis(ethoxycarbonyl)-1-methyl-1,2-dihydroquinolines while most derivatives react with oxalyl chloride to give substituted 1-methyl-4 phenylbenzo[f][1,4]diazepine-2,3-dicarboxylic anhydrides.     

Asymmetric Coupling of Carbon-Centered Radicals Adjacent to Nitrogen: Copper-Catalyzed Cyanation and Etherification of Enamides

The first copper-catalyzed asymmetric cyanation and etherification reactions of enamides have been established, where a carbon-centered radical adjacent to a nitrogen atom (CRAN) is enantioselectively trapped by a chiral copper(II) species. Moreover, the asymmetric cyanation of vinyl esters was disclosed as well. These reactions feature very mild reaction conditions and high functional group tolerance, and give a series of chiral α-cyano amides, α-cyano esters and α-hemiaminals in good yields with excellent enantioselectivity. The chiral α-cyano amides can be easily converted into enantioenriched 1,2-diamines and amino acids.     

The reaction of aromatic dialdehydes with enantiopure 1,2-diamines: an expeditious route to enantiopure tricyclic amidines

The condensation of enantiopure 1,2-diamines with terephthalaldehyde, isophthalaldehyde or 2-iodo-, 2-alkyl- or 2-aryl-1,3-benzenedialdehydes in toluene followed by treatment with NBS in dichloromethane gives direct access to enantiopure 1,4-, and 1,3-di(4,5-dihydro-1H-imidazol-2-yl)benzenes (diamidines). The condensation of o-phthalaldehyde, and other ortho-disubstituted aromatic dialdehydes, with enantiopure 1,2-diamines, without NBS, gives enantiopure 3,5-dihydro-2H-imidazol-[2,1]-isoindoles.     

Influence of the metal and chiral diamine on metal(II)salen catalysed, asymmetric synthesis of α-methyl α-amino acids

The influence of the metal ion and chiral diamine used to form a metal(salen) complex on the catalytic activity of the complex in the asymmetric benzylation of an alanine enolate was investigated. Only metal ions which could form square-planar complexes gave catalytically active complexes, and best results were obtained with metal ions from the first row of transition metals, particularly copper(II) and cobalt(II). Salen ligands derived from acyclic, chiral 1,2-diamines were found to generate poor catalysts, an effect which seems to correlate with the ability of the substituents within the diamine to adopt a conformation in which they are anti to one another. Complexes derived from a variety of 5- and 6-membered cyclic 1,2-diamines did form active catalysts, but the enantioselectivity was always far lower than that of the parent cyclohexane-1,2-diamine derived complex.     

Synthesis and Structure of New 2-(2-Quinolyl)-1,3-tropolone Derivatives

4,6-Di-tert-butyl-3-nitro-1,2-benzoquinone reacts with substituted 2-methylquinolines to give the corresponding 2-(2-quinolyl)-4-nitro-1,3-tropolones and 2-(2-quinolyl)-1,3-tropolones.     

Reactions of 2-polyfluoroalkylchromones with aliphatic diamines

2-Polyfluoroalkylchromones react with aliphatic 1,2-diamines to give 2,3-dihydro-1H-1,4-diazepines. A similar reaction with 1,3-diaminopropane yieldsN,N′-trimethylenebis(2-hydroxyacetophenomines) as a result of scission of the original chromones. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 817–819, April, 1999.     

Cyclic dithio-carbenium ion salts and their conversion to ketene dithioacetals

1,2-Ethanedithiol and 1,3-propanedithiol were treated with perchloric acid in acetic anhydride to give 2-methyl-1,3-dithiolan-2-yl and 2-methyl-1,3-dithian-2-yl perchlorates, respectively, which were converted to ketene dithioacetals by deprotonation with tertiary amines.     

Regio- and stereoselective C-2 and C-3 cleavage of 2-(1-aminoalkyl)aziridines with alcohols, carboxylic acids, and sodium iodide

Ring opening of nonactivated aziridines 1 using several nucleophiles, such as alcohols, carboxylic acids, and sodium iodide, is described. Depending on the nucleophile used, aziridines 1 are cleaved at C-3 or C-2 with total regio- and stereoselectivity, affording chiral 2-alkoxy-1,3-diamines 2 with alcohols, or O-acylated-1-hydroxy-2,3-diamines 6 with carboxylic acids in moderate or high yield. In the case of the aziridines derived from phenylalanine, treatment with NaI afford trans-4-phenylbut-3-en-1,2-diamines 9, generating the alkene with total diastereoselectivity. Mechanisms have been proposed to explain these reactions.     

Catalytic highly enantioselective 1,3-dipolar cycloaddition reaction of nitrones with 3-alkenoyl-2-oxazolidinones by use of a bidentate chiral bis(imine) ligand–Cu(II) triflate complex

A copper(II) triflate complex with bidentate, chiral C₂-symmetric cyclohexane-1,2-bis[(2,6-dichlorophenylmethylene)amine] catalyzed the 1,3-dipolar cycloaddition reactions of nitrones with electron-deficient dipolarophiles, 3-(2-alkenoyl)-1,3-oxazolidin-2-ones to give isoxazolidine cycloadducts with extremely high endo- and enantioselectivities.     

Direct asymmetric hydroxyamination reaction catalyzed by an axially chiral secondary amine catalyst

A direct asymmetric hydroxyamination reaction of aldehydes with nitrosobenzene was found to be catalyzed by the novel axially chiral secondary amine catalyst (S)-1d. The resulting optically enriched hydroxyamination products were readily converted to beta-amino alcohols or 1,2-diamines in one pot.     

Dimerization and isomerization reactions of alpha-lithiated terminal aziridines

The scope of dimerization and isomerization reactions of alpha-lithiated terminal aziridines is detailed. Regio- and stereoselective deprotonation of simple terminal aziridines with lithium 2,2,6,6-tetramethylpiperidide (LTMP) or lithium dicyclohexylamide (LiNCy2) generates trans-alpha-lithiated terminal aziridines. These latter species can then undergo dimerization or isomerization reactions depending on the nature of the N-protecting group. alpha-Lithiated terminal aziridines bearing N-alkoxycarbonyl (Boc) protection undergo N- to C-[1,2] migration to give N-H trans-aziridinylesters. In contrast, aziridines bearing N-organosulfonyl [tert-butylsulfonyl (Bus)] protection undergo rapid dimerization to give 2-ene-1,4-diamines or, if a pendant alkene is present, diastereoselective cyclopropanation to give 2-aminobicyclo[3.1.0]hexanes. All of these reactions were used as key steps in the preparation of synthetically and biologically important targets.     

Chiral calcium organophosphate-catalyzed enantioselective electrophilic amination of enamides

Highly enantioselective direct amination of enamides catalyzed by chiral nonracemic calcium bis(phosphate) complex 3g afforded optically active 1,2-hydrazinoimines 4. Following a subsequent in situ hydrolysis or reduction, 2-hydrazinoketones 5 or syn-1,2-disubstituted 1,2-diamines 6 were obtained in high yields and excellent enantiomeric excess.     

De novo synthesis of Tamiflu via a catalytic asymmetric ring-opening of meso-aziridines with TMSN3

An asymmetric ring-opening reaction of meso-aziridines with TMSN3 was developed using a catalyst prepared from Y(OiPr)3 and chiral ligand 2 in a 1:2 ratio. Excellent enantioselectivity was realized from a wide range of substrates with a practical catalyst loading. The products were efficiently converted to enantiomerically enriched 1,2-diamines, which are versatile chiral building blocks for pharmaceuticals and chiral ligands. This reaction was applied to a catalytic asymmetric synthesis of Tamiflu, a very important anti-influenza drug containing a chiral 1,2-diamino functionality.