Solid-phase synthesis of aryl, heteroaryl, and sterically hindered alkyl amines using the Curtius rearrangement

An efficient method for the solid-phase synthesis of aryl amines, heteroaryl amines, and sterically hindered alkyl amines has been developed. The key step in this process was the formation of resin-bound carbamates (B) by the Curtius rearrangement of aryl carboxylic acids with Wang resin providing the trapping hydroxyl group. N-Alkylation reactions of B gave secondary amines in good yield. Some biaryl amines, which are found widely in biologically active substances, were also prepared by the Suzuki reaction of resin-bound carbamates of 2-iodoaniline (16) or 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (21). The developed methods can be applied to the preparation of libraries containing aryl, heteroaryl, and sterically hindered alkyl amine structures as the pharmacophores.     

Palladium-catalyzed arylation of malonates and cyanoesters using sterically hindered trialkyl- and ferrocenyldialkylphosphine ligands.

Palladium-catalyzed reactions of aryl bromides and chlorides with two common stabilized carbanions-enolates of dialkyl malonates and alkyl cyanoesters-are reported. An exploration of the scope of these reactions was conducted, and the processes were shown to occur in a general fashion. Using P(t-Bu)(3) (1), the pentaphenylferrocenyl ligand (Ph(5)C(5))Fe(C(5)H(4))P(t-Bu)(2) (2), or the adamantyl ligand (1-Ad)P(t-Bu)(2) (3), reactions of electron-poor and electron-rich, sterically hindered and unhindered aryl bromides and chlorides were shown to react with diethyl malonate, di-tert-butyl malonate, diethyl fluoromalonate, ethyl cyanoacetate, and ethyl phenylcyanoacetate. Although alkyl malonates and ethyl alkylcyanoacetates did not react with aryl halides using these catalysts, the same products were formed conveniently in one pot from diethylmalonate by cross-coupling of an aryl halide in the presence of excess base and subsequent alkylation.     

Synthesis of sterically hindered phenolic compounds from indole and its derivatives

Reactions of 3,5-di-tert-butyl-4-hydroxybenzyl acetate with indole and its derivatives gave a series of sterically hindered phenolic compounds having various functional groups. The products are potentially capable of inhibiting radical chain oxidation processes according to different mechanisms.     

Functional derivatives of sterically hindered amines. 1. Glycidyl compounds

Four polymerizable glycidyl derivatives of sterically hindered amines were prepared from derivatives of 2, 2, 6, 6-tetramethyl-4-hydroxypiperidine and 14, 16-dioxo-7, 15-diazadispiro [5, 1, 5, 3] hexadecane. One of them is a stable nitroxyl derivative.     

An efficient synthesis of sterically hindered arylboronic acids

Boronic acids are important intermediates and molecular recognition moieties in a wide variety of applications. In our research, we have found that the synthesis of ortho-substituted arylboronic acids is problematic with the commonly used bis(pinacolato)diboron in palladium-mediated borylation reactions. As a substitute, we have found that bis(neopentyl glycolato)diboron is a much more efficient borylation agent for the synthesis of sterically hindered ortho-substituted arylboronic acids.     

Novel synthesis of sterically hindered N-substituted lactams from imides

An efficient and practical synthesis of sterically hindered N-substituted lactams has been developed starting from simple starting materials. The stereochemistry of the synthetically useful N,N acetal intermediate has been established.     

Regiospecific oxidation by DDQ of unhindered alkyl groups in sterically hindered aromatic amines

DDQ oxidises an unhindered activated alkyl group to a carbonyl or a hydroxymethyl group depending on the nature of the substitution, in a sterically hindered aromatic amine.     

Palladium-catalyzed synthesis of indole fused coumarins via cross-dehydrogenative coupling

The present method describes a palladium-catalyzed cross-dehydrogenative coupling reaction of coumarin and aniline for the synthesis of indole fused coumarin derivatives. The one-pot method is operationally simple and molecular oxygen is used as sole oxidant. The target compounds are obtained in good yields from commercially available precursors.     

Facile synthesis of sterically hindered and electron-deficient secondary amides from isocyanates

The big easy: The direct coupling of Grignard reagents to isocyanates provides a facile and robust solution for the synthesis of sterically hindered and electron-deficient secondary amides. The products are obtained in high yields without the need for excess reagents or chromatographic purification.     

Isatin acylhydrazones with sterically hindered phenolic fragments: synthesis and structures

Isatin acylhydrazones with sterically hindered phenolic fragments were obtained. Their structures were determined using 1D and 2D 1H and 13C NMR spectroscopy and X-ray diffraction. The products synthesized by condensation of isatin and 1-(3,5-di- tert-butyl-4-hydroxybenzyl)-l H-indole-2,3-dione with 3-(3,5-di- tert-butyl-4-hydroxyphenyl)propiono-hydrazide exist as E- and Z-isomers about the C=N bond. E— Z isomerization takes place in boiling ethanol. The E-isomer of the condensation product from isatin and 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionohydrazide was structurally characterized using X-ray diffraction: this isomer is a cis-conformer about the amide group and has a E-configuration about the N—N bond. According to data on the concentration dependence of the signals for the NH protons in the 1H NMR spectra, the acylhydrazones obtained are stabilized in solution by intra-and intermolecular hydrogen bonding.     

High-pressure transesterification of sterically hindered esters

A mild, rapid, and efficient method for the solvolysis of sterically hindered esters under high pressure is described. Transesterification is carried out in the presence of DBU at room temperature and at a pressure of 10 kbar to give quantitative conversions within short reaction times. The substrates examined included aromatic and aliphatic esters of sterically hindered alcohols and phenols. An optically pure benzyl ester of phenylalanine was chosen to study racemization of the amino acid esters under high-pressure reaction conditions.     

Self-addition of a sterically hindered alkynylselenolate

[structure: see text] The unprecedented formation of a complex macrocyclic selenium-carbon ring system, which is initiated by the action of coordinating reagents upon a sterically hindered alkynylselenolate, has been observed. The crystal structure of the product could be obtained and shows a rigid tricyclic arrangement consisting only of selenium and sp(2)-hybridized carbon atoms. This reactivity stands in contrast to the corresponding unsubstituted alkynylselenolates and is an example where a bulky substituent destabilizes an adjacent unsaturated pi-system.     

Utilizing o-quinone methide chemistry: synthesis of sterically hindered acridin-4-ols

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Microwave-assisted synthesis of sterically hindered 3-(5-tetrazolyl)pyridines

Sterically hindered 2,4-disubstituted 3-(5-tetrazolyl)pyridines were efficiently prepared from the corresponding nicotinonitriles using microwave technology.     

Reactivity of a sterically hindered Fe(II) thiolate dimer with amines and hydrazines

The sterically hindered Fe(II) thiolate dimer Fe(2)(mu-STriph)(2)(STriph)(2) (1; [STriph](-) = 2,4,6-triphenylbenzenethiolate) reacts with primary amines ((t)BuNH(2), aniline) and N(2)H(4) to form the structurally characterized addition complexes Fe(STriph)(2)(NH(2)(t)Bu)(2), Fe(2)(mu-STriph)(2)(STriph)(2)(NH(2)Ph)(2), and Fe(2)(mu-eta(1):eta(1)-N(2)H(4))(2)(N(2)H(4))(4)(STriph)(4) in high yield. Chemical and NMR spectroscopic evidence indicate that the binding of these nitrogen donors is labile in solution and multispecies equilibria are likely. With arylhydrazines, 1 catalytically disproportionates 1,2-diphenylhydrazine to aniline and azobenzene, and it rearranges 1-methyl-1,2-diarylhydrazines to give, after treatment with alumina, mononuclear, trigonal bipyramidal Fe(III) complexes of composition Fe(ISQ)(2)(STriph), where [ISQ](-) denotes an appropriately substituted bidentate o-diiminobenzosemiquinonate ligand. Complex 1 shows no reaction with hindered 1,2-dialkylhydrazines (isopropyl or tert-butyl) or tetrasubstituted 1,2-dimethyl-1,2-diphenylhydrazine.     

Quantum-chemical analysis of the mechanism of action of sterically hindered amines in photostabilization of polyolefins

A quantum-chemical study was made of the reaction of sterically hindered amines with the degradation products of polyolefins. The reactivity indices of these compounds and the formation energies of their reaction products were calculated by the semiempirical CNDO/2 and MINDO/3 methods. The mechanism of the photostabilizing action of sterically hindered amines was substantiated theoretically. The criteria by means of which it is possible to determine their relative reactivities were established, and the role of the substituent was determined. The results are compared with experimental data on the photostabilizing effectiveness of these compounds.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 25, No. 5, pp. 594–597, September–October, 1989.     

Aquametric microdetermination of sterically hindered ketones

Conclusions The previously developed aquametric micromethod for determining carbonyl compounds also gives reliable results when most of the sterically hindered ketones studied by us are analyzed. The determination error is ±0.3%.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 942–944, April, 1972.