Sensitive Functional Groups Research Articles

ChemInform Abstract: Synthesis of 1,8‐Diazaanthracenes as Building Blocks for Internally Functionalized Aromatic Oligoamide Foldamers.

The synthesis of a variety of 9-functionalized 1,8-diazaanthracene diesters and amino acids is described. Derivatization at the 9-position relies on facile reactions performed on the 9-chloro and 9-bromomethyl precursors. This has allowed the incorporation of nucleophilic or sensitive functional groups that otherwise cannot be incorporated under standard methods for synthesizing these compounds. Additionally, the synthesis of the protected amino acids via a high-yielding monosaponification and subsequent Curtius rearrangement has been accomplished on a multigram scale. These units, together with the functionalized derivatives, should prove to be useful monomers in the synthesis of aromatic oligoamide foldamers.

Nickel‐Catalyzed One‐Pot Suzuki–Miyaura Cross‐Coupling of Phenols and Arylboronic Acids Mediated by N,N‐Ditosylaniline

AbstractAn efficient method for the construction of two distinct Caryl–Caryl bonds through the Ni‐catalyzed Suzuki–Miyaura cross‐coupling of phenols with arylboronic acids has been developed. This reaction proceeds through the in situ tosylation of phenols by using N,N‐ditosylaniline as the sulfonylating reagent, which is highly active, markedly stable, and easily prepared. The scope with respect to the coupling partners – phenols and boronic acids – is broad, and sensitive functional groups are tolerated. Phenols, especially those containing an unprotected amino group, which are generally problematic for coupling under conventional one‐pot conditions, are also viable substrates in this transformation.

2+2] cycloaddition of 1,3-dienes by visible light photocatalysis.

[2+2] photocycloadditions of 1,3-dienes represent a powerful yet synthetically underutilized class of reactions. We report that visible light absorbing transition metal complexes enable the [2+2] cycloaddition of a diverse range of 1,3-dienes. The ability to use long-wavelength visible light is attractive because these reaction conditions tolerate the presence of sensitive functional groups that might be readily decomposed by the high-energy UVC radiation required for direct photoexcitation of 1,3-dienes. The resulting vinylcyclobutane products are poised for a variety of further diversification reactions, and this method is consequently expected to be powerfully enabling in the synthesis of complex organic targets.

2+2] Cycloaddition of 1,3‐Dienes by Visible Light Photocatalysis

Abstract[2+2] Photocycloadditions of 1,3‐dienes represent a powerful yet synthetically underutilized class of reactions. We report that visible light absorbing transition metal complexes enable the [2+2] cycloaddition of a diverse range of 1,3‐dienes. The ability to use long‐wavelength visible light is attractive because these reaction conditions tolerate the presence of sensitive functional groups that might be readily decomposed by the high‐energy UVC radiation required for direct photoexcitation of 1,3‐dienes. The resulting vinylcyclobutane products are poised for a variety of further diversification reactions, and this method is consequently expected to be powerfully enabling in the synthesis of complex organic targets.

ChemInform Abstract: Nucleophilic Addition to N‐Alkoxyamides

AbstractReview: 9 refs.

Magnetically separable silica@Fe3O4 core–shell supported nano-structured copper(II) composites as a versatile catalyst for the reduction of nitroarenes in aqueous medium at room temperature

In this paper, the fabrication of a highly efficient magnetically separable organic–inorganic hybrid nanocatalyst has been reported by covalently immobilizing the copper(II) acetylacetonate complex over amine functionalized silica@magnetite nanoparticles. The prepared nanocatalyst was characterized by electron microscopy techniques (SEM and TEM with EDS), X-ray diffraction (XRD), vibrational sampling magnetometer (VSM), Fourier transform infrared spectroscopy (FT-IR) and atomic absorption spectroscopy (AAS) techniques. The catalytic performance of the resulting nano-composites was examined for the degradation of various organic nitro-analogues in aqueous medium at room temperature using sodium-borohydride as the source of hydrogen. This nano-catalytic system selectively reduces the nitro group even in presence of other sensitive functional groups. To achieve the best catalytic efficacy, various parameters such as catalyst loading, reaction time, effect of various bases and solvents etc. were optimized. The reaction kinetics for the reduction of o-nitroaniline to benzenediamine was studied by UV–vis spectroscopy, and its apparent rate constant was determined and compared with different copper nanocatalysts. The identification of organic residues and purity of the obtained products was analysed by GC–MS. The acquisition of this nanocatalyst has been demonstrated by employing the catalyst in hot filtration and reusability test, and the results obtained from the tests show negligible metal leaching. The nano-catalytic system can be efficiently recovered using simple magnet and reused for multiple cycles without appreciable loss in its catalytic activity. In addition, the stability of the recycled catalyst has been proved by SEM and VSM techniques. It is noteworthy that the key-features like mild reaction conditions, simple work-up procedure, high turnover frequency (TOF), no use of toxic organic solvents, ease in recovery and reusability of the catalyst makes the present protocol more fascinating from an environmental and economic point of view.

A very mild and selective method for O-benzoylation of hydroxamic acids

Selective O-benzoylation of hydroxamic acids is achieved by the treatment of BPO and DABCO. Aliphatic alcohols are not reactive under these conditions. Various radical or oxidation sensitive functional groups are compatible with this protocol, and no anhydrous reagents or solvents are required for the high yields of the benzoylations.

ChemInform Abstract: A New Gold‐Catalyzed Azidation of Allenes.

AbstractThis highly modular gold‐catalyzed reaction fails for allenes containing acid sensitive functional groups.

Synthetic Studies towards Radicicol through Biomimetic Macrolactonization and Transannular Aromatization Reactions

AbstractStudies towards the total synthesis of the natural product radicicol are described that employ a late‐stage esterification and aromatization by trapping a ketene intermediate. The subsequent biomimetic aromatization of the resultant triketo ester gave highly functionalized resorcylates. Two distinct methods were examined that trap the ketene intermediate through either an intermolecular or intramolecular process. In the first approach, the synthesis of the resorcylate was followed by a ring‐closing metathesis, which gave the macrolactone and protected precursors to monocillin I. In the second approach, an intramolecular ketene trapping was examined as an alternative to close the macrocycle and form the resorcylate macrolactone. These studies showcased a wide range of sensitive functional groups that tolerated the aromatization reaction conditions, which started from the corresponding dioxinone precursors.

Asymmetric palladium-catalyzed allylic alkylation using dialkylzinc reagents: a remarkable ligand effect.

A serendipitously discovered palladium-catalyzed asymmetric allylic alkylation reaction with diorganozinc reagents, which displays broad functional group compatibility, is reported. This novel transformation hinges on a remarkable ligand effect which overrides the standard "umpolung" reactivity of allyl-palladium intermediates in the presence of dialkylzincs. Owing to its mild conditions, enantioselective allylic alkylations of racemic allylic electrophiles are possible in the presence of sensitive functional groups.

A highly efficient Cu-catalyzed S-transfer reaction: from amine to sulfide.

A highly efficient Cu-catalyzed dual C-S bonds formation reaction, proceeding in alcohol and water under air, is reported, in which inodorous stable Na2S2O3 is used as a sulfurating reagent. This powerful strategy provides a practical and efficient approach to construct thioethers, using readily available aromatic amines and alkyl halides as starting materials. Sensitive and synthetic useful functional groups could be tolerated. Furthermore, pharmaceuticals, glucose, an amino acid, and a chiral ligand are successfully furnished by this late-stage sulfuration strategy.

Enantioselective Enzymatic Hydrolysis of rac-Mandelonitrile to R-Mandelamide by Nitrile Hydratase Immobilized on Poly(vinyl alcohol)/Chitosan–Glutaraldehyde Support

Nitriles, amides and carboxylic acids have varied applications in active pharmaceutical intermediate (API), drug and chemical industry, and particularly in the synthesis of pure enantiomers of chiral compounds. The chemical hydrolysis of nitrile compounds is well studied, but it necessitates harsh conditions along with the protection of sensitive functional groups, which on deprotection leads to generation of a large amount of byproducts. Immobilization of nitrile hydratase using a novel support reduces the cost and allows green processes. In this work, enantioselective hydrolysis of rac-mandelonitrile was studied using poly(vinyl alcohol) (PVA)/chitosan–glutaraldehyde cross-linked Rhodococcus rhodochrous ATCC BAA-870 nitrile hydratase (NHase). Immobilized NHase converted rac-mandelonitrile to (R)-amide by dynamic kinetic resolution with enantiomeric excess (ee) up to 81%. The temperature of 40 °C and pH 8 were found to be optimum for the enantioselective nitrile hydrolysis. In the presence of various cosolvents, immobilized NHase showed higher retention of activity in methanol compared to other cosolvents. The kinetic constants for free and immobilized enzyme were obtained from the Lineweaver–Burk plot. The immobilized NHase was found to be reusable up to nine successive batch reactions.

NiXantphos: a deprotonatable ligand for room-temperature palladium-catalyzed cross-couplings of aryl chlorides.

Although the past 15 years have witnessed the development of sterically bulky and electron-rich alkylphosphine ligands for palladium-catalyzed cross-couplings with aryl chlorides, examples of palladium catalysts based on either triarylphosphine or bidentate phosphine ligands for efficient room temperature cross-coupling reactions with unactivated aryl chlorides are rare. Herein we report a palladium catalyst based on NiXantphos, a deprotonatable chelating aryldiphosphine ligand, to oxidatively add unactivated aryl chlorides at room temperature. Surprisingly, comparison of an extensive array of ligands revealed that under the basic reaction conditions the resultant heterobimetallic Pd–NiXantphos catalyst system outperformed all the other mono- and bidentate ligands in a deprotonative cross-coupling process (DCCP) with aryl chlorides. The DCCP with aryl chlorides affords a variety of triarylmethane products, a class of compounds with various applications and interesting biological activity. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of aryl chloride substrates bearing heteroaryl groups and sensitive functional groups that are known to undergo 1,2-addition, aldol reaction, and O-, N-, enolate-α-, and C(sp2)–H arylations. The advantages and importance of the Pd–NiXantphos catalyst system outlined herein make it a valuable contribution for applications in Pd-catalyzed arylation reactions with aryl chlorides.

Unsustainable cattle load in alpine pastures alters the diversity and the composition of lichen functional groups for nitrogen requirement

Despite their considerable relevance as biodiversity hotspots, alpine ecosystems are presently threatened by several anthropogenic disturbances. Among these, pasture-derived nitrogen deposition is expected to significantly alter community composition and diversity of many sensitive organisms, such as lichens. We analysed patterns of γ-diversity components in epilithic lichen communities of pasturelands in the Maritime Alps (north-west Italy). Our aims were: (1) to estimate the shift in functional groups for nitrogen tolerance along a gradient of increasing cattle load; (2) to establish the cattle critical load. High cattle load reduced the species replacement and significantly increased the similarity in the oligotrophic component of the lichen communities. The oligotrophic component was the most sensitive functional group to nitrogen. Based on the relative abundance of oligotrophs we set the cattle critical load of the area at 0.12 grazing animals per hectare.

C–H Methylation of Heteroarenes Inspired by Radical SAM Methyl Transferase

A practical C–H functionalization method for the methylation of heteroarenes is presented. Inspiration from Nature’s methylating agent, S-adenosylmethionine (SAM), allowed for the design and development of zinc bis(phenylsulfonylmethanesulfinate), or PSMS. The action of PSMS on a heteroarene generates a (phenylsulfonyl)methylated intermediate that can be easily separated from unreacted starting material. This intermediate can then be desulfonylated to the methylated product or elaborated to a deuteriomethylated product, and can divergently access medicinally important motifs. This mild, operationally simple protocol that can be conducted in open air at room temperature is compatible with sensitive functional groups for the late-stage functionalization of pharmacologically relevant substrates.

ChemInform Abstract: Synthesis of Structurally Diverse Polyfunctional Pyrrolo[1,2‐a]quinolines by Sequential Iron‐Catalyzed Three‐Component Coupling and Gold‐Catalyzed Hydroarylation Reactions.

A simple and efficient synthesis of complex pyrrolo[1,2-a]quinoline derivatives was achieved through sequential reactions that involved an iron(III)-catalyzed synthesis of N-(2-alkynylaryl)pyrroles and a gold(III)-catalyzed intramolecular hydroarylation reaction. This strategy tolerated a wide range of substrates with a variety of sensitive functional groups and afforded the corresponding pyrrolo[1,2-a]quinoline derivatives in moderate to good yields. The ease of availability of the starting materials and the generality of the reaction sequences make it a highly attractive strategy to synthesize a diverse range of pyrrolo[1,2-a]quinoline derivatives. Moreover, a preliminary photophysical study showed that the resulting molecules exhibit good fluorescence activity.

Synthesis of 1,8-Diazaanthracenes as Building Blocks for Internally Functionalized Aromatic Oligoamide Foldamers

The synthesis of a variety of 9-functionalized 1,8-diazaanthracene diesters and amino acids is described. Derivatization at the 9-position relies on facile reactions performed on the 9-chloro and 9-bromomethyl precursors. This has allowed the incorporation of nucleophilic or sensitive functional groups that otherwise cannot be incorporated under standard methods for synthesizing these compounds. Additionally, the synthesis of the protected amino acids via a high-yielding monosaponification and subsequent Curtius rearrangement has been accomplished on a multigram scale. These units, together with the functionalized derivatives, should prove to be useful monomers in the synthesis of aromatic oligoamide foldamers.

Rhodium(I)‐Catalyzed Decarbonylative Spirocyclization through CC Bond Cleavage of Benzocyclobutenones: An Efficient Approach to Functionalized Spirocycles

AbstractThe rhodium‐catalyzed formation of all‐carbon spirocenters involves a decarbonylative coupling of trisubstituted cyclic olefins and benzocyclobutenones through CC activation. The metal–ligand combination [{Rh(CO)2Cl}2]/P(C6F5)3 catalyzed this transformation most efficiently. A range of diverse spirocycles were synthesized in good to excellent yields and many sensitive functional groups were tolerated. A mechanistic study supports a hydrogen‐transfer process that occurs through a β‐H elimination/decarbonylation pathway.

Rhodium(I)-catalyzed decarbonylative spirocyclization through C-C bond cleavage of benzocyclobutenones: an efficient approach to functionalized spirocycles.

The rhodium-catalyzed formation of all-carbon spirocenters involves a decarbonylative coupling of trisubstituted cyclic olefins and benzocyclobutenones through CC activation. The metal-ligand combination [{Rh(CO)2 Cl}2 ]/P(C6 F5 )3 catalyzed this transformation most efficiently. A range of diverse spirocycles were synthesized in good to excellent yields and many sensitive functional groups were tolerated. A mechanistic study supports a hydrogen-transfer process that occurs through a β-H elimination/decarbonylation pathway.

ChemInform Abstract: Molecularly designed Architectures — The Metalloligand Way

AbstractReview: 316 refs.