Alkyl Diazoacetates Research Articles

Stereoselective Synthesis of Kalafungin Based on CuI‐Catalyzed Tandem Reactions of Arylethynes Containing an Ortho‐(1‐Hydroxyethyl) Substituent with Alkyl Diazoacetates

AbstractAn isochromene synthesis is developed utilizing a cascade reaction involving a CuI catalyzed coupling reaction between an alkyne and diazoacetate followed by allenoate isomerization and subsequent oxa‐Michael addition. The cascade sequence was also demonstrated for the synthesis of naphthalenes. Furthermore, the methodology developed herein was applied toward a stereoselective synthesis of pyranonaphthoquinone kalafungin.magnified image

Polymerization of Alkyl Diazoacetates Initiated by Pd(Naphthoquinone)/Borate Systems: Dual Role of Naphthoquinones as Oxidant and Anionic Ligand for Generating Active Pd(II) Species

For polymerization of alkyl diazoacetates, the combination of a Pd complex bearing 1,4-naphthoquinone (NQ) or its derivatives as a ligand and borate, NaBPh4, was found to be an efficient initiating system. The polymerization of ethyl diazoacetate by a Pd(0) complex having two NQ molecules [Pd(nq)2] with NaBPh4 proceeded to give poly(ethoxycarbonylmethylene)s with a relatively high molecular weight (up to Mn = 36 kDa) in good yield (∼70%). This initiating system was also effective for polymerizing other diazoacetates, benzyl and cyclohexyl diazoacetates. In addition, in the presence of NaBPh4, a novel Pd(II) complex bearing an anionic naphthoquinonyl ligand derived from 2,3-dichloro-1,4-naphthoquinone (dichlone), [Pd(cod)(Cl-nq)Cl] (cod = 1,5-cyclooctadiene), which was newly prepared by treatment of a Pd(0) precursor, Pd2(dba)3·CHCl3 [dba = (E,E)-dibenzylideneacetone], with COD and dichlone, was capable of affording poly(alkoxycarbonylmethylene)s with much higher stereoregularity compared to the previously...

Synthesis of functionalized pyrazole derivatives by regioselective [3+2] cycloadditions ofN-Boc-α-amino acid-derived ynones

Abstract[3+2] cycloadditions of ynones derived from glycine and (S)-alanine and some other dipolarophiles with azomethine imines, nitrile oxides, diazoacetate, and azidoacetate were studied. The dipolarophiles were obtained fromα-amino acids, either by the reduction of the carboxy function with ethynylmagnesium bromide or by propiolation of the amino function. Cu-catalyzed cycloadditions of ynones to azomethine imines were regioselective and gave the expected cycloadducts as inseparable mixtures of diastereomers. In some instances, further oxidative hydrolytic ring-opening took place to afford 3,3-dimethyl-3-(1H-pyrazol-1-yl)propanoic acids. Acid-catalyzed cycloadditions of 3-butenone were also regioselective and provided mixtures of diastereomeric cycloadducts, which were separated by chromatography. In the reactions of title ynones with alkyl diazoacetates,in situ-formed benzonitrile oxides, andtert-butyl azidoacetate, all cycloadducts were obtained as single regioisomers. The structures of all novel compounds were established by nuclear magnetic resonance and X-ray diffraction.

Chiral Brønsted Acid‐Catalyzed Asymmetric Synthesis of N‐Aryl‐cis‐aziridine Carboxylate Esters

AbstractWe report a multi‐component asymmetric Brønsted acid‐catalyzed aza‐Darzens reaction which is not limited to specific aromatic or heterocyclic aldehydes. Incorporating alkyl diazoacetates and, important for high ee's, ortho‐tert‐butoxyaniline our optimized reaction (i.e. solvent, temperature and catalyst study) affords excellent yields (61–98 %) and mostly >90 % optically active cis‐aziridines. (+)‐Chloramphenicol was generated in 4 steps from commercial starting materials. A tentative mechanism is outlined.

Chiral Brønsted Acid-Catalyzed Asymmetric Synthesis of N-Aryl-cis-aziridine Carboxylate Esters.

We report a multi‐component asymmetric Brønsted acid‐catalyzed aza‐Darzens reaction which is not limited to specific aromatic or heterocyclic aldehydes. Incorporating alkyl diazoacetates and, important for high ee's, ortho‐tert‐butoxyaniline our optimized reaction (i.e. solvent, temperature and catalyst study) affords excellent yields (61–98 %) and mostly >90 % optically active cis‐aziridines. (+)‐Chloramphenicol was generated in 4 steps from commercial starting materials. A tentative mechanism is outlined.

Polymerization of alkyl diazoacetates initiated by the amidinate/Pd system: efficient synthesis of high molecular weight poly(alkoxycarbonylmethylene)s with moderate stereoregularity

The initiating ability of a new system, amidinate/Pd, for the polymerization of diazoacetates is described.

Copolymerization of alkyl diazoacetates with α,β-unsaturated aldehydes: synthesis and application

Copolymerization of alkyl diazoacetates with α,β-unsaturated aldehydes and the product's fluorescence property.

Catalytic Activity of Novel Vitamin B12 Derivatives

Among many biologically important metals, Co, in the form of vitamin B12 (cyano-cobalamin), plays a unique role. B12 coenzymes are indispensable for catalyzing enzymatic rearrangements (coenzyme B12, adenosylcobalamin) and methylation reactions (methylcobalamin).1 The special ability of vitamin B12 and other corrinoids to form a Co-C bond, combined with its facility in furnishing alkyl radicals via homolysis, has attracted the interest of many researchers, because corrinoids can be used as catalysts for C-C-bond forming reactions, which belong to the most challenging processes in organic synthesis. These catalytic reactions typically involve alkyl-cobalt complexes, which are formed in reactions of Co(I) species and an electrophile or a Co(II) and a radical. The most common chemical procedure utilizes the ‘supernucleophilicity’ of the Co(I) species (B12s) toward alkylating agents, such as alkyl halides. Homolysis of the Co-C bond generates a carbon-centered radical, which can, in situ, disproportionate, abstract H˙, or self-couple. In these reactions, B12 alkyl derivatives can be considered ‘reversible carriers’ of an alkyl radical.4 We have developed the synthesis of novel cobalamin derivatives possessing modified substituents at the periphery of the molecule. Our methodology presents a unique situation in which the six peripheral amide groups are transformed while leaving the bottom “f-loop” intact.2 These derivatives displayed UV-Vis spectra and oxidation-reduction characteristics similar to those of vitamin B12 but they differed significantly from the”incomplete” corrinoid heptamethyl cobyrinate, where the nucleotide moiety is absent, and instead, the second cyanide is coordinated. We confirmed that the intramolecular coordinating ligand plays a role in the radical reactions catalyzed by vitamin B12 derivatives. For example, the microwave-assisted homocoupling of benzylbromide3 catalyzed by cobalester produced a higher yield when compared to reactions catalyzed by reduced (CN)2Cob(OMe)7.Furthermore, the amphiphilic character of these newly synthesized derivatives facilitates carbon insertion into the vinyl C-H bond of olefins with alkyl diazoacetates in the presence of light. 1. Banerjee, R. Chemistry and Biochemistry of B12, John Wiley & Sons, Inc, 1999 2. Proinsias ó, K.; Giedyk, M.; Sharina, I.G.; Martin, E. and Gryko, D. ACS Med. Chem. Lett. 2012, 3, 476. 3. Giedyk, M.; Fedosov, S.; Gryko, D. Chem. Commun. 2014, 50, 4674-4676. 4. Shey, J.; McGinley, Ch.M.; McCauley, K.M.; Dearth, A.S.; Young, B.T. and van der Donk, W.A. J. Org. Chem. 2002, 67, 837. Figure 1

Polymerization of Alkyl Diazoacetates Initiated with Pd Complexes

SummaryPd‐initiated polymerization of alkyl diazoacetates as an effective methodology to prepare carbon‐carbon (CC) main chain polymers bearing a substituent on every main chain carbon is described. (NHC)Pd/borate (NHC = N‐heterocyclic carbene) systems are efficient at affording high Mn polymers. π‐AllylPdCl‐based systems can initiate the polymerization with the number of polymer chain per Pd ratios over 1.0 because of occurrence of chain transfer, capable of affording relatively low Mn polymers in high yield. Initiation and termination mechanisms have been proposed for the latter initiating systems, based on the detailed MALDI‐TOF‐MS analyses of the low Mn products.

ChemInform Abstract: Interceptive [4 + 1] Annulation of in situ Generated 1,2‐Diaza‐1,3‐dienes with Diazo Esters: Direct Access to Substituted Mono‐, Bi‐, and Tricyclic 4,5‐Dihydropyrazoles.

AbstractA Cu(II)‐catalyzed [4 + 1] annulation reaction of α‐halo N‐acyl hydrazones with alkyl diazoacetates is developed to allow the synthesis of trisubstituted pyrazolines.

ChemInform Abstract: Catalytic Carbon Insertion into the β‐Vinyl C—H Bond of Cyclic Enones with Alkyl Diazoacetates.

AbstractA novel Lewis acid‐promoted Csp2‐H functionalization reaction of cyclic enones using various diazoacetates is described.

Catalytic Carbon Insertion into the β-Vinyl C–H Bond of Cyclic Enones with Alkyl Diazoacetates

The first example of the boron Lewis acid catalyzed C(sp2)-H functionalization of cyclic enones was achieved using diazoacetates. The insertion of the carbon atom of diazoacetates utilizes BF3•Et2O or a newly designed oxazaborolidinium ion as a catalyst to afford β-functionalized cyclic enones from simple cyclic enones in a single step and high yields. The reaction mechanism was investigated with deuterium labeled 2-cyclohexen-1-one.

A simple criterion for gas chromatography/mass spectrometric analysis of thermally unstable compounds, and reassessment of the by‐products of alkyl diazoacetate synthesis

A principal limitation of gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) is the thermal instability of analytes. We propose that the injector and column temperatures should not exceed the atmospheric pressure boiling point, without decomposition, of the highest homologue of the series being analyzed, instead of the time-consuming procedure of obtaining chromatograms using different temperatures. A series of thermally unstable diazocarbonyl compounds, alkyl diazoacetates (predicted limit of stability approx. 140 °C, the boiling point of ethyl diazoacetate), was selected for GC/MS analysis using standard equipment. Different GC separation conditions were selected so that the retention temperatures of target compounds were both below and above 140 °C. Analyzing alkyl diazoacetates within their thermal stability range permitted reanalysis of their typical synthesis by-products. No dialkyl fumarate or maleate impurities, principal decomposition products which have often been reported previously, were found. Instead, alkyl esters of glycolic acid nitrate, O(2)NOCH(2)CO(2)R, and 'pseudo-dimeric' products, ROCO[C(2)H(3)NO]CO(2)R, were discovered for the first time. Avoiding the decomposition of thermally unstable organic compounds during GC and/or GC/MS analysis requires estimating their degradation temperature limits. This limit can be estimated as being equal to the atmospheric pressure boiling point of the highest homologue in the homologous series under consideration that does not decompose on boiling.

π-AllylPdCl-Based Initiating Systems for Polymerization of Alkyl Diazoacetates: Initiation and Termination Mechanism Based on Analysis of Polymer Chain End Structures

Polymerization of ethyl and benzyl diazoacetates (EDA and BDA) initiated with π-allylPdCl-based systems [π-allylPdCl/NaBPh4, π-allylPdCl/NaBArF4 (ArF = 3,5-{CF3}2C6H3), and π-allylPdCl] is described. Initiation efficiencies of the π-allylPdCl-based systems are much higher than those of the previously reported (NHC)Pd/borate (NHC = N-heterocyclic carbene) systems, and the new systems are capable of polymerizing the alkyl diazoacetates at low temperatures(0 ∼ −20 °C), where the (NHC)Pd/borate systems cannot initiate the polymerization. MALDI–TOF–MS analyses of the polymers obtained from EDA provide information for the chain-end structures of the polymers, based on which initiation and termination mechanisms are proposed. Interestingly, EDA polymerization by the π-allylPdCl-based systems in the presence of alcohols (EtOH, nPrOH, and nBuOH) or water was found to afford RO- or HO-initiated polymers as major products, as confirmed by MALDI–TOF–MS analyses.

A Regioselective Synthesis of Multi-Substituted 2-Imino-1,3-oxazolines by One-Pot Reaction

Heterocycles are significant chemical entities for research on small molecule drugs and their development in the pharmaceutical industry. Attention until now has focused on synthetic methods for forming heterocycles. However, new and efficient synthetic methods for the construction of heterocyclic molecules are now being researched continuously. In our previous papers, we reported the construction of two different combinatorial libraries, including novel 2imino-1,3-thiazolines 1, that show T-type calcium channel inhibitory activity and fungicidal property. Recently, a number of reports examined the significant biological activities of the 2-imino-1,3-thiazoline derivatives. As an extension of our efforts to investigate the biological activities of their analogues, we synthesized 2-imino-1,3-oxazolines 2, which are isosteres of 2-imino-1,3-thiazolines 1 (Figure 1). In the present study we investigate a method for synthesizing multi-substituted 2-imino-1,3-oxazolines 2 with the aim of increasing the diversity in chemical structures. A comparison of the biological activity of 1 and 2 promises to increase our understanding of the structure-activity relationship of this series. A literature survey revealed few reports on the synthetic methods of 2-imino-1,3-oxazolines. The synthetic methodologies of 2-imino-1,3-oxazolines reported over the past three decades were classified into four categories. First, a condensation of α-haloketone and symmetrical diphenylurea in presence of bromine as the condensing agent gave 2-arylimino-3-aryl-1,3-oxazolines. Second, electrochemical synthesis of substituted phenylmonoimine with N-acylcarbonimidoyl dichloride resulted in tetraaryliminooxazolines. Third, the reaction of ketenimine with hydroxylamino derivatives gave 2-imino-1,3-oxazolines through 3-iminoisoxazolines. Fourth, the reaction of alkyl diazoacetates with carbodiimides in presence of transition metal salts gave 2-imino-1,3-oxazoline derivatives. Unfortunately, all these reported methods suffered the limitations of low yield, harsh reaction conditions, and lack of regioselectivity and chemical structural diversity of the products. Therefore, we herein report a very simple and convenient synthetic method for the preparation of multi-substituted 2-imino-1,3-oxazolines derivatives with the aim of increasing the product diversity and production yield, by reacting α-hydroxyketone and carbodiimide in the presence of copper salts as a catalyst.

Stereoselective synthesis of cis- and trans-2′,5′-disubstituted N-arylpyrrolo[3′,4′:1,9](C60-I h )[5,6]fullerenes by the 1,3-dipolar cycloaddition of azomethine ylides from dialkyl aziridinedicarboxylates to fullerene C60

A stereoselective method for the synthesis of 2′,5′-disubstituted N-arylpyrrolofullerenes from anilines, alkyl glyoxylates, alkyl diazoacetates, and fullerene C60 was proposed. The key step of the synthesis is the 1,3-dipolar cycloaddition reaction of fullerene with azomethine ylides generated by heating of dialkyl aziridinedicarboxylates. The thermal opening of the aziridine ring to azomethine ylide and the cycloaddition of the latter to C60 at 100 °C are nearly completely stereoselective: only trans-adducts are formed from cis-aziridines, whereas trans-aziridines give exclusively cis-adducts.

Oxazaborolidinium Ion-Catalyzed Cyclopropanation of α-Substituted Acroleins: Enantioselective Synthesis of Cyclopropanes Bearing Two Chiral Quaternary Centers

A catalytic synthetic route to highly functionalized chiral cyclopropane derivatives was developed by Michael-initiated cyclopropanation of α-substituted acroleins with aryl- and alkyl diazoacetates. In the presence of chiral (S)-oxazaborolidinium cation 1b as a catalyst, the reaction proceeded in high yield (up to 93%) with high to excellent diastereoselectivity (up to 98% de) and enantioselectivity (up to 95% ee).

Generation and exploitation of acyclic azomethine imines in chiral Brønsted acid catalysis

Successful implementation of a catalytic asymmetric synthesis strategy to produce enantiomerically enriched compounds requires the adoption of suitable prochiral substrates. The combination of an azomethine imine electrophile with various nucleophiles could give straightforward access to a number of synthetically useful chiral hydrazines, but is used rarely. Here we report the exploitation of acyclic azomethine imines as a new type of prochiral electrophile. They can be generated in situ by the condensation of N'-benzylbenzoylhydrazide with a variety of aldehydes in the presence of a catalytic amount of an axially chiral dicarboxylic acid. By trapping these electrophiles with alkyl diazoacetate or (diazomethyl)phosphonate nucleophiles, we produced a diverse array of chiral α-diazo-β-hydrazino esters and phosphonates with excellent enantioselectivities.

Polymerization of Various Alkyl Diazoacetates Initiated with (N-Heterocyclic Carbene)Pd/Borate Systems

(NHC)Pd/borate initiating systems (NHC = N-heterocyclic carbene) were applied for polymerization of alkyl diazoacetates with a variety of ester groups. The monomers with n-hexyl, cyclohexyl, benzyl, and cholesteryl group as an ester group were transformed into the corresponding poly(alkoxycarbonylmethylene)s with Mn > 10 000. On the other hand, the polymerization of 1-adamantyl diazoacetate afforded low-Mn polymers (Mn < 4000), probably because of steric reasons. Copolymerization of a few comonomer combinations also proceeded successfully to give copolymers with Mn > 20 000.

ChemInform Abstract: Asymmetric Synthesis of Lactones with High Enantioselectivity by Intramolecular Carbon-Hydrogen Insertion Reactions of Alkyl Diazoacetates Catalyzed by Chiral Rhodium(II) Carboxamides.

ChemInform Abstract: Asymmetric Synthesis of Lactones with High Enantioselectivity by Intramolecular Carbon-Hydrogen Insertion Reactions of Alkyl Diazoacetates Catalyzed by Chiral Rhodium(II) Carboxamides.