A novel and efficient synthesis of chiral C2-symmetric 1,4-diamines

A novel and efficient method for synthesis of (R,R)- and (S,S)-C₂-symmetric 1,4-diamines was established. The key steps are a combination of Pinacol Coupling and Corey-Winter olefination.     

Synthesis of C2-symmetric chiral crown ethers by lipase-catalyzed reactions

Kinetic resolution of a racemic mixture of C₂-symmetric 18-crown-6 diols (rac-1a) and 15-crown-5 diol (rac-1c) was achieved by lipase-catalyzed acetylation. The enantiomeric excess of the chiral crown diols (95% ee and 82% ee) was determined by ¹H NMR spectroscopy, using (R)-(+)-1-(1-naphthyl)ethylammonium hydrochloride as a shift reagent. The C₂-symmetric chiral 15-crown-5 diol (>95% ee) was also obtained by kinetic resolution of the racemic diacetate (rac-2c) using lipase-catalyzed solvolysis.     

Asymmetric allylation of N-benzoylhydrazones promoted by novel C2-symmetric bis-sulfoxide organocatalysts

Novel C₂-symmetric bis-sulfoxide/N-oxide (R,R)-5 was prepared in good yield according to the Andersen protocol with (S)-menthyl p-tolyl sulfinate (2 equiv) and the dilithium derivate of 2,6-dimethylpyridine N-oxide. Reduction of (R,R)-5 to pyridine/bis-sulfoxide (R,R)-6 was accomplished by means of Katritzky’s procedure (Fe⁰/AcOH). Both bis-sulfoxides (R,R)-5 and (R,R)-6 are efficient chiral organocatalysts in the asymmetric allylation of N-benzoyl hydrazones derived from both aldehydes and ketones.     

Asymmetric alkylation of 5-alkyl-2-aminothiazolones using a C2-symmetric chiral tetraamine base

The diastereoselective alkylation of a series of 5-alkyl-2-aminothiazolones utilizing a C₂-symmetric chiral tetraamine base is reported.     

Novel C2-symmetric chiral 18-crown-6 derivatives with two aromatic sidearms as chiral NMR discriminating agents

Novel C₂-symmetric chiral 18-crown-6 derivatives with two aromatic sidearms 2-4 were prepared, and their enantiomeric recognition abilities as chiral NMR discriminating agents towards primary ammonium salts were examined. Among these chiral crown ethers, the most effective enantiomeric discrimination of racemic ammonium salts in the ¹H NMR spectra was attained by the derivative with two pyrenylmethyl sidearms.     

Synthesis of C1-symmetric chiral tripodal oxazolines through an oxazoline exchange reaction with amino alcohols

Various C₁-symmetric chiral tripodal tris(oxazolines) with two different oxazoline units were synthesized from chiral C₃-symmetric tris(oxazolines) through an oxazoline exchange reaction with amino alcohols in the presence of zinc chloride. Evaluation of the new oxazolines as chiral molecular receptor showed that some of the receptors have chiral discrimination ability.     

Studies in stereoselective [2+2]-cycloadditions with dichloroketene

During the investigation of the reaction of dichloroketene with cyclic enoxy-lactones and acyclic enoxy-ester substrates it was found that only the acylic variants effectively participated in the [2+2]-cycloaddition. Although a complete understanding of the reasons for this are lacking, molecular mechanics calculations do suggest that an out of plane twist of the cabonyl group in the acyclic compounds may be partially responsible. After screening a variety of chiral auxiliaries it was found that useful levels of diastereoselectivity (2.6-10.8:1) could be obtained in this cycloaddition reaction when (R)-2,2-diphenylcyclopentanol was used as the chiral auxiliary.     

Catalytic enantioselective [2+2]-cycloaddition reaction of 2-methoxycarbonyl-2-cyclopenten-1-one by chiral copper catalyst

A new catalytic system for enantioselective [2+2]-cycloaddition reaction of 2-methoxycarbonyl-2-cyclopenten-1-one with thioacetylene derivatives is described. The use of a catalytic amount (20-30 mol%) of copper(II) salt with chiral bis-pyridine ligand was found to be effective in promoting the [2+2]-cycloaddition reaction, furnishing the corresponding bicyclic compound in good yield and good enantioselectivity.     

Concise synthesis of the core structure of madreporanone by Rh-catalyzed [3+2] cycloaddition

A model study toward total synthesis of madreporanone, a novel diterpene isolated from Azorella madreporica, was investigated. The [3.3.0] bicyclic core of madreporanone bearing a cis-configured isopropyl group and two vicinal quaternary carbon centers was stereoselectively constructed via an intramolecular Rh-catalyzed [3 + 2] cycloaddition in a single step.     

Synthesis of cis bis-β-lactams via Staudinger cycloaddition reaction using C2-symmetric 1,2-diamines

An efficient stereoselective synthesis of bis-β-lactams via cycloaddition reaction (Staudinger reaction) of ketenes with bisimines derived from C₂-symmetric 1, 2-diamines is described. The reaction provided diastereomeric mixture of meso and C₂-symmetric cis-bis-β-lactams with higher selectivity for meso-bis-β-lactams.     

Efficient synthesis of chiral C2-symmetric diamines via allylboration of bis-N,N′-metallodiimines

An enantioselective synthesis of C₂-symmetric bis-homoallylic aromatic and heteroaromatic diamines in 54-89% yields, in 73-94% de and ?98% ee has been achieved via the allylboration of the corresponding N,N′-bis(trimethylsilyl)dialdimines and N,N′-bis(diisobutylalumino)dialdimines with B-allyldiisopinocampheylborane in the presence of methanol, followed by alkaline hydrogen peroxide workup. One-pot synthesis of stable N,N′-bis(benzaldimine-triethylborane) complexes and subsequent allylboration to afford benzene diamines is also described.     

Synthesis and applications of C2-symmetric guanidine bases

The preparation of the tetracyclic C₂-symmetric guanidinium salts 5 and 11-13 is reported together with their application to enantioselective transformations.     

Synthesis and chiroptical property of C2-symmetric cyclohexapyrrole

Condensation reaction of gem-dimethyldipyrrylmethane-5,5′-dicarbinol and 4,4′-dimethyl-3,3′-di-iso-butyl-2,2′-bipyrrole under the catalysis by trifluoroacetic acid gave a hexapyrrolic macrocycle 6 in 15% yield after DDQ oxidation. X-ray crystallography of 6 shows that three parts of highly planar dipyrrylmethene unit are assembled by two sp³ hybridized gem-dimethyl carbon bridges and one direct linking at the pyrrole α-positions, leading to C₂ molecular symmetry. The complexation of 6 with (S)-(+)- and (R)-(−)-mandelic acid induced a CD Cotton effect at 461 and 650 nm.     

Target cum flexibility: synthesis of C(3′)-spiroannulated nucleosides

We report a simple strategy for the synthesis of a collection of C(3′)-spirodihydroisobenzo-furannulated nucleosides featuring a [2+2+2]-cyclotrimerization as the key reaction. The cyclotrimerization reactions are facile with the unprotected nucleosides having a diyne unit. When both alkynes of the diyne are terminal, the regioselectivity is poor. However, when one of the terminal alkynes is additionally substituted, the cyclotrimerizations are highly diastereoselective. Since the key bicycloannulation is the final step, this strategy provides flexibility in terms of the alkynes and is thus amenable for the synthesis of a focussed small molecule library.     

Synthesis of C3- and C2-symmetric tris- and bis-sulfoxide ligands by asymmetric oxidation

A series of tris- and bis-sulfoxides were synthesized by multiple asymmetric oxidation of the corresponding sulfides. High enantioselectivities were obtained based on Horeau-type amplification of selectivity. Naphthyl-substituted sulfoxides allowed for higher selectivity and greater ease of purification. These sulfoxides were tested as ligands in rhodium-catalyzed olefin hydroacylation and 1,4-addition of phenyl boronic acid to 2-cyclohexen-1-one. While no enantioinduction was observed in hydroacylation, up to 80% ee was obtained for a tris-sulfoxide and a bis-sulfoxide ligand in the 1,4-addition. Bis-sulfoxides with flexible backbones gave lower and inversed enantioselectivity, suggesting backbone rigidity plays a key role in enantioinduction.     

Synthesis and unusual [2+2]-cycloaddition reactions of ethyl 4-chloro-2-oxobut-3-ynoate with unactivated alkenes

The highly activated acetylenes, ethyl 4-chloro-2-oxobut-3-ynoate and ethyl 4-bromo-2-oxobut-3-ynoate, were prepared from readily available bis(trimethylstannyl)acetylene in two steps with high overall yield. An unusual ability of the former to furnish [2+2]-cycloadducts with 1,1-disubstituted alkenes in the absence of irradiation and catalysts was discovered. The cycloaddition of ethyl 4-chloro-2-oxobut-3-ynoate to the 1,2-disubstituted alkenes was shown to be effectively catalyzed with stannic chloride.     

Conceptually new chiral tertiary C2 symmetric diamines in asymmetric synthesis

New chiral diamines were prepared, based on the cyclohexane diamine core. The two different substituents on each nitrogen allow this heteroatom to become a stereogenic center upon chelation with a metal, such as lithium. The enantioselective addition of MeLi to imines, with ee's up to 68%, illustrates the validity of this concept.     

A novel way to chiral 2-oxazolidinones: selenium-catalyzed cyclocarbonylation of 2-aminoethanols

Selenium-catalyzed cyclocarbonylation of 2-aminoethanols with CO under atmospheric pressure at 30 °C afforded 2-oxazolidinones in excellent yields without any other co-catalyst. The method was then applied to the syntheses of chiral 2-oxazolidinones and no racemization was detected.     

Synthesis and structure of C2-symmetric N-heterocyclic carbene complexes of palladium

The first 9- and 11-membered cis and trans C₂-symmetric benzimidazol-2-ylidene palladium(II) complexes based on a trans-2,2-dimethyl-1,3-dioxalane backbone were synthesised and the configuration of the complexes was elucidated via NMR and X-ray crystallography.     

Novel C1-symmetric chiral crown ethers bearing rosin acids groups: synthesis and enantiomeric recognition for ammonium salts

Four types of novel C₁-symmetric chiral crown ethers including 28-crown-8, 20-crown-6, 17-crown-5 and 14-crown-3 (9a–m) were synthesized and their enantiodiscriminating abilities with protonated primary amines (10–14) were examined by ¹H NMR spectroscopy. 20-crown-6 crown ethers exhibited good chiral recognition properties toward these guests and showed different complementarity to some chiral guests, indicating that 20-crown-6 crown ethers could be used as a chiral NMR solvating agent to determine the enantiopurity of these guests. In addition, the binding model and binding site between the hosts and guests were also studied by the computational modeling and experimental calculation.