The Ugi reaction with CF3-carbonyl compounds: effective synthesis of α-trifluoromethyl amino acid derivatives

The Ugi reaction with CF₃-carbonyl compounds is described in detail. The method is efficient for the multicomponent preparation of α-trifluoromethyl (Tfm) amino acids, α-Tfm containing dipeptides, and iminodicarboxylic acids. In addition, the first protected CF₃-opine derivative was prepared. The scope, limitations, and stereochemistry of the approach are discussed.     

Transition metal-catalyzed formation of CF3-substituted α,β-unsaturated alkene and the synthesis of α-trifluoromethyl substituted β-amino ester

A new transition metal-catalyzed formation of CF₃-substituted α,β-unsaturated alkenes through the ylide intermediate from the reaction between methyl 3,3,3-trifluoro-2-diazopropionate 1 and aryl aldehydes has been developed. Further transformation of the alkene affords the α-trifluoromethyl substituted β-amino ester, a valuable intermediate in the synthesis of fluorine-containing amino acids with potential biological application.     

Efficient synthesis of an α-trifluoromethyl-α-tosyloxymethyl epoxide enabling stepwise double functionalisation to afford CF3-substituted tertiary alcohols

The efficient synthesis of an α-trifluoromethyl-α-tosyloxymethyl epoxide is reported. This highly versatile building block may be reacted sequentially with two different nucleophiles to furnish α-trifluoromethyl tertiary alcohols. Furthermore, the two enantiomers of this key intermediate have been separated using chiral HPLC and the stereochemistry shown to be conserved during subsequent chemical manipulations. Finally, an enzyme-driven desymmetrisation approach has been successfully employed to confer chirality on an intermediate in the sequence.     

CpRu-catalyzed O-H insertion and condensation reactions of α-diazocarbonyl compounds

[CpRu(CH(3)CN)(3)][PF(6)] and diimine ligands catalyze together the decomposition of α-diazocarbonyl compounds leading to O-H insertion and condensation reactions. In comparison with Rh(II) and Cu(I) complexes, the CpRu catalysts produce rapid and often more selective reactions. Promising enantioselectivities are obtained in dioxole syntheses.     

Reactions of 3-aroylacrylates with α-aminoazoles*

Dihydro derivatives of pyrazolo[3,4-b]pyridine-, pyrazolo[1,5-a]pyrimidine-, and [1,2,4]triazolo-[1,5-a]pyrimidinecarboxylates have been prepared by cyclocondensation of β-aroylacrylates with 5-aminopyrazoles and 3-amino-1,2,4-triazole. Heating dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7-carboxylates with hydrazine hydrate led to recyclization of the pyrimidine ring to form 6-arylpyridazin-3(2H)-ones.     

Natural scaffolds-inspired synthesis of CF3-substituted macrolides enabled by Rh-catalyzed C–H alkylation macrocyclization

The development of innovative strategies and methods to provide natural product-like macrocycles not accessible by biosynthesis, but endowed with novel bioactivities and simplified structure, is highly desirable. Inspired by the key scaffolds of rapamycin and FR252921, herein, we report a Rh（III）-catalyzed C–H alkylation macrocyclization, which enables access to CF3-substituted macrolides. DFT calculations reveal that the chemoselectivity between C–H alkylation and olefination macrocyclization w...     

Rh-catalyzed intermolecular reactions of cyclic α-diazocarbonyl compounds with selectivity over tertiary C-H bond migration

Intermolecular Rh-catalyzed reactions of cyclic α-diazocarbonyl compounds with chemoselectivity over β-hydride elimination are described. These methods represent the first general intermolecular reactions of Rh-carbenoids that are selective over tertiary β-C-H bond migration. Successful transformations include cyclopropanation, cyclopropenation, and various X-H insertion reactions with a broad scope of substrates. We propose that the intermolecular approach of substrates to carbenes from acyclic diazo precursors may be relatively slow due to a steric interaction with the ester function, which is perpendicular to the π-system of the carbene. For carbenes derived from five- and six-membered cyclic α-diazocarbonyls, it is proposed that the carbene is constrained to be more conjugated with the carbonyl, thereby relieving the steric interaction for intermolecular reactions, and accelerating the rate of intermolecular reactivity relative to intramolecular β-hydride migration. However, attempts to use α-diazo-β-ethylcaprolactone in intermolecular cyclopropanation with styrene were unsuccessful. It is proposed that the conformational flexibility of the seven-membered ring allows the carbonyl to be oriented perpendicular to Rh-carbene. The significant intermolecular interaction between the carbonyl and approaching substrate is in agreement with the poor ability of α-diazo-β-ethylcaprolactone to participate in intermolecular cyclopropanation reactions. DFT calculations provide support for the mechanistic proposals that are described.     

Reactions of cyanofurazans with β-dicarbonyl compounds

In the presence of nickel acetylacetonate, -dicarbonyl compounds readily add at the nitrile group of 4-R-3-cyanofurazans to form enaminofurazans. The adducts obtained from 4-amino-3-cyanofurazan underwent intramolecular cyclization on heating with AcOH in EtOH to give furazano[3,4-b]pyridine derivatives in high yields.     

Reactions of α-halonitrosoalkanes with resorcinol

-Halonitrosoalkanes react with resorcinol as nitrosylating agents to form 3-hydroxy-N-(2,4-dihydroxyphenyl)-1,4-quinone imine.Translated fromIzvestiya Akademioi Nauk. Seriya Khimicheskaya, No. 3, pp.773–774, March, 1996.     

Gold-catalyzed synthesis of β-trifluoromethylated α,β-unsaturated ketones from CF3-substituted propargylic carboxylates and their reactivity in Diels-Alder reactions

The synthesis of fluorinated synthetic intermediates has become a field of intense research in organic chemistry. In this article, we report the application of a gold-catalyzed rearrangement to the synthesis of β-trifluoromethylated α,β-unsaturated ketones. The scope of the reaction, as well as the valorization of the products in subsequent transformations has been investigated. This study allowed for the preparation of various CF₃-substituted enones and fluorinated Diels-Alder adducts from easily accessible starting materials.     

Reactions of α-nitroacrylates with thiophenols

Reactions of α-nitroacrylates with aromatic thiols like 4-methyl- and 4-chlorothiophenols afford a series of new 3-arylsulfanyl-2-nitropropanoates. The latter were isolated as diastereomerically pure substances or mixtures of two diastereomers. Structures of the obtained S-adducts were confirmed by IR, ¹H and ¹³C-{¹H} NMR spectroscopy using HMQC and HMBC experiments.     

Lewis acid-promoted reactions of ethenetricarboxylates with γ-CF3-substituted propargyl alcohols

The Lewis acid-promoted reaction of an ethenetricarboxylate derivative (1) with CF₃-substituted propargyl alcohols has been examined. Reaction of γ-CF₃ propargyl alcohols in the presence of zinc bromide gave five-membered CF₃-containing tetrahydrofurans in 66-85% yield. The CF₃ group activates alkyne as an electron-withdrawing group. On the other hand, reaction of γ-trifluoromethyl-α-aryl propargyl alcohols 2 with 1 in the presence of 1 equiv of SnCl₄ gave cyclobutane derivatives 6 in 29-49% yield. Formation of cyclobutane 6a arises from the [2+2] cycloaddition between ethenetricarboxylate 1 and chloroallene 8, which is produced by the reaction of propargyl alcohol 2a and SnCl₄.     

Quantum chemical study of α-diazocarbonyl bullvalene derivatives and related heterocyclic compounds

According to the results of PBE0/cc-pVTZ quantum chemical calculations, the equilibrium mixture of α-diazocarbonyl bullvalene derivatives (C₁₀H₈N₂O) contains an impurity of the corresponding bullvaleno-[1,2,3]oxadiazoles. The carbonyl group in the major tautomer is conjugated with the three-membered ring. The concentration of other tautomers in the equilibrium mixture of two bullvaleno[1,2,3]selenadiazoles is negligible.     

Reactions of aminoguanidine with α-dicarbonyl compounds studied by electrospray ionization mass spectrometry

Aminoguanidine possesses extensive pharmacological properties. This drug is recognized as a powerful α-dicarbonyl scavenger. In order to better elucidate the reactivity of aminoguanidine with α-dicarbonyls, aminoguanidine was reacted with several aldehydic and diketonic α-dicarbonyls. Electrospray ionization mass spectrometry is a suitable technique to study chemical and biochemical processes, and was selected for the purpose. In aminoguanidine reactions, triazines were detected and, other compounds that have never been reported before were identified. Triazine precursor forms were detected, namely tetrahydrotriazines and singly dehydrated tetrahydrotriazines. Moreover, species with bicyclic ring structures, and dehydrated forms, were also identified in aminoguanidine reactions. These species appear to result from tetrahydrotriazines and triazines reactions with one dicarbonyl molecule. Experiments revealed that these bicyclic species, in particular the ones resulting from triazines reactivity, could exist in solution, since they were both identified in the reactions of aminoguanidine and of a selected triazine with the dicarbonyls studied. The results obtained, regarding aminoguanidine/triazines reactivities, appear to support the capability of triazines to condensate and form polycyclic ring structures, and also to support literature mechanistic data for dihydroimidazotriazines formation via dihydroxyimidazolidine-triazines. The data obtained in this study may prove to be valuable to complement solution information, concerning the reactivity of amines with α-dicarbonyls, in particular.     

Reactions of 1,2-diaminobenzimidazoles with β-dicarbonyl compounds

The reactions of 1,2-diaminobenzimidazoles with β-dicarbonyl compounds give 1,2,4-triazepino [2,3-a]benzimidazole and pyrimido [1,2-a]benzimidazole-derivatives.     

Reactions of alkylidenepyrrolidines with α-chlorooximes and α-chlorohydrazones

The reactions of alkylidenepyrrolidines with α-chlorooximes give isoxazoles via an acylation reaction followed by ring isomerisation. In contrast, and in line with a previous report, the corresponding α-chlorohydrazones give the simple acylation products, although in one instance a cycloadduct was also obtained.