Palladium-catalyzed synthesis of 2-substituted benzothiazoles via a C-H functionalization/intramolecular C-S bond formation process

Catalytic synthesis of 2-substituted benzothiazoles from thiobenzanilides was achieved in the presence of a palladium catalyst through C-H functionalization/C-S bond formation. This method features the use of a novel catalytic system consisting of 10 mol % of Pd(II), 50 mol % of Cu(I), and 2 equiv of Bu4NBr that produced variously substituted benzothiazoles in high yields with good functional group tolerance.     

Photochemical synthesis of 2-substituted benzothiazoles

The photochemical reaction of 1 -indolethiocarbanilides 1 , di- and tri-substituted thioureas 3–5 and 4,4 -di-methyl-2,6-dioxothiocyclohexanecarboxanilides 9 affording the respective benzothiazoles are described.     

Room-temperature C-H arylation: merger of Pd-catalyzed C-H functionalization and visible-light photocatalysis

This communication describes the development of a room-temperature ligand-directed C-H arylation reaction using aryldiazonium salts. This was achieved by the successful merger of palladium-catalyzed C-H functionalization and visible-light photoredox catalysis. The new method is general for a variety of directing groups and tolerates many common functional groups.     

Liquid-phase synthesis of 2-substituted benzimidazoles, benzoxazoles and benzothiazoles

A novel acid fluoride for use in the liquid-phase synthesis of substituted benzimidazoles, benzoxazoles and benzothiazoles was developed. Its synthetic utility is exemplified by a structurally diverse set of aromatic heterocycles. Final cleavage is achieved by treatment with sodium methoxide in methanol for 12 h. The corresponding benzimidazoles, benzoxazoles and benzothiazoles were obtained in good isolated yields (22-62%, four steps).     

Eco-friendly synthesis of 2-substituted benzothiazoles catalyzed by silica sulfuric acid

2-Substituted benzothiazoles have been synthesized via one-pot reaction from aromatic aldehydes and o-aminothiophenol catalyzed by silica sulfuric acid in absolute methanol at room temperature. The remarkable advantages offered by this method are an environmentally friendly and reusable catalyst, a simple procedure, mild conditions, short reaction times, and good to excellent yields of products.     

C-H functionalization logic in total synthesis

In this critical review, the strategic and economic benefits of C-H functionalization logic will be analyzed through the critical lens of total synthesis. In order to illustrate the dramatically simplifying effects this type of logic can potentially have on synthetic planning, we take the reader through a series of case studies in which it has already been successfully applied. In the first section, a chronological look at key historical syntheses will be examined, leading into modern day examples. In the second section, our own experience with applying and executing synthesis with a C-H functionalization "mindset" will be discussed (114 references).     

Cu(II) catalyzed imine C-H functionalization leading to synthesis of 2,5-substituted 1,3,4-oxadiazoles

A direct access to symmetrical and unsymmetrical 2,5-disubstituted [1,3,4]-oxadiazoles has been accomplished through an imine C-H functionalization of N-arylidenearoylhydrazide using a catalytic quantity of Cu(OTf)(2). This is the first example of amidic oxygen functioning as a nucleophile in a Cu-catalyzed oxidative coupling of an imine C-H bond. These reactions can be performed in air atmosphere and moisture making it exceptionally practical for application in organic synthesis.     

Oxidative Csp3-H functionalization of 2-methylazaarenes: A practical synthesis of 2-azaarenyl-benzimidazoles and benzothiazoles

Oxidative C_sp3-H functionalization of 2-methylazaarenes using I₂-DMSO in open flask has been described first time for the synthesis of 2-azaarenyl benzimidazoles and 2-azaarenyl benzothiazoles. Generally, methyl group of 2-methylazaarenes serves as a carbon nucleophile and in this work the methyl group served as electrophilic carbon (umpolung!) and condensed with o-Phenylenediamine and 2-aminothiophenol to furnish the corresponding benzimidazoles and benzothiazoles in high yields with good substrate scope and functional group tolerance.     

The carbene insertion methodology for the catalytic functionalization of unreactive hydrocarbons: no classical C-H activation, but efficient C-H functionalization

This contribution intends to highlight the use of the metal-catalyzed functionalization of unreactive carbon-hydrogen bonds by the carbene insertion methodology, that employs diazo compounds as the carbene source.     

Novel C-H functionalization of arenes: palladium-catalyzed synthesis of diaryl sulfides

A novel protocol for the direct arylthiolation of electron-rich arenes is described. Applying arylsulfonyl cyanides in the presence of catalytic amounts of Pd allows for a straightforward synthesis of diaryl sulfides.     

One-pot synthesis of tricyclo-1,4-benzoxazines via visible-light photoredox catalysis in continuous flow

A facile one-pot synthesis of tricyclo-1,4-benzoxazines has been developed via metal-free intramolecular cyclization of indole derivates. These reactions were efficiently achieved at ambient temperature by using visible-light photoredox catalysis in continuous flow. This directed intramolecular cyclization could be easily handled and scaled up in an open flask, enabling construction of a focused compound library for further pharmacological evaluation.     

Kinetic resolution and double stereodifferentiation in catalytic asymmetric C-H activation of 2-substituted pyrrolidines

Dirhodium tetrakis(S-(N-dodecylbenzenesulfonyl)prolinate) (Rh(2)(S-DOSP)(4)) catalyzed decomposition of methyl aryldiazoacetates in the presence of 2-substituted pyrrolidines results in highly diastereoselective and enantioselective C-H insertions. These reactions can proceed with impressive levels of double stereodifferentiation and kinetic resolution, which allows for three stereocenters to be controlled during the C-H insertion step.     

Application of a catalytic palladium biaryl synthesis reaction, via C-H functionalization, to the total synthesis of Amaryllidaceae alkaloids

The total synthesis of the Amaryllidaceae alkaloids dehydroanhydrolycorine, hippadine, pratosine, anhydrolycorine, assoanine, anhydrolycorin-7-one and oxoassoanine was achieved from the appropriate N-benzylisatin precursors using an intramolecular, palladium catalyzed, dehydrohalogenation, biaryl synthesis reaction to establish the carbon skeleton of the natural products. In order to avoid the formation of regioisomers in the cyclization reactions it was found necessary to incorporate the halogen on the benzyl group. Borane reduction of the 7H-pyrrolo[3,2,1-de]phenanthridine-4,5-dione derivatives gave 7H-pyrrolo[3,2,1-de]- and 4,5-dihydro-7H-pyrrolo[3,2,1-de]-phenanthridines (dehydroanhydrolycorine, dehydroassoanine, anhydrolycorine and assoanine). The former were readily reduced to the latter with NaCNBH₃ to give anhydrolycorine and assoanine. These compounds were then oxidized to anhydrolycorin-7-one and oxoassoanine whilst the same mixtures of borane reduction products could be oxidized to give hippadine and pratosine.     

One-pot copper-catalyzed synthesis of 2-substituted benzothiazoles from 2-iodoanilines,benzyl chlorides and elemental sulfur

An efficient one-pot three-component reaction of 2-iodoanilines, benzyl chlorides and elemental sulfur to form 2-substituted benzothiazoles in satisfactory yields (up to 98%) has been described. The reaction tolerated a wide range of functional groups on the aromatic ring. And heterocycle methylene chlorides substrates were also found to be compatible.     

A simple and efficient synthesis of 2-substituted benzothiazoles catalyzed by H_2O_2/HCl

A simple and efficient procedure for the synthesis of substituted benzothiazoles through condensation of 2-aminothiophenol with aromatic aldehydes in the presence of H_2O_2/HCl system in ethanol at room temperature is described.The target compounds have been characterized by ~1H NMR,~(13)C NMR,IR and MS.Short reaction time,easy and quick isolation of the products,and excellent yields are the main advantages of this procedure.     

Mass-spectrometric study of sulfenamide derivatives of 2-substituted benzothiazoles

It is shown that the dissociative ionization of 2-mercaptobenzothiazole derivatives with a sulfenamide bond is accompanied by cleavage of the labile N-S bond and simultaneous migration of the hydrogen atom from the thiol substituent at the site of cleavage to the sulfur atom. Ion peaks with mass 167, 166, R, and (R-H), where R is an N-substituted cycloalkylamine, are maximum peaks and are used for the identification of the compounds.Translated from Khimiya Geterotsiklicheskikh Soedmenii, No. 10, pp. 1330–1336, October, 1975.     

1,3-Diol synthesis via controlled, radical-mediated C-H functionalization

The invention of a method for the synthesis of 1,3-diols from the corresponding alcohols is described, via controlled, radical-mediated C-H functionalization. The sequence described herein entails near quantitative conversion to the corresponding trifluoroethyl carbamate, followed by a variant of the Hofmann-L?ffler-Freytag reaction, cyclization, and hydrolysis to provide the 1,3-diols. In addition to the 10 examples presented herein, the syntheses of four natural products are facilitated by this directed oxyfunctionalization. This methodology is demonstrated to be orthogonal to other known C-H oxidations. Finally, this sequence is efficient, practical, inexpensive, and scalable.