Sulfonyl azides, with active

One popular method in the synthesis of a-diazo ketones is in the base-catalyzed diazo group transfer reaction of sulfonyl azides with activated dicarbonyl compounds The Regitz Diazo Reaction) While direct diazo transfer to ketone enolates is usually not feasible, a two step deformylative diazo transfer strategy has been employed, whereby a ketone is first... 

The reaction of sulfonyl azides with terminal alkynes is an interesting exception. Whereas aryl and alkyl azides react with activated alkynes to give the corresponding 1,2,3-triazoles, intermediate sulfonyltriazoles result in the formation of different products. In the presence of amines, N-sulfonyl azides are converted to M-sulfonyl amidines, whereas under aqueous conditions, M-acylsulfonamides are the major products [76-78]. Nevertheless, Fokin et al. reported conditions for the successful formation of N -sulfonyl-1,2,3-triazoles 105 shown in Scheme 22 [79]. 

Sulfonyl azides are exceptional in that they do not normally give triazoles with activated methylene compounds nucleophilic attack by the carbanion is usually followed by loss of the sulfonamide anion, giving a diazo compound as the product. Possible mechanisms for the reaction are illustrated (Scheme 8) for diethyl malonate. Attack of the carbanion on the terminus of the azide gives the anion of the linear triazene (1). 

Triazoles have also been obtained when the carbon atom adjacent to the activated methylene group carries a nitrogen function (i.e., amides, nitriles, amidines, and imines - ). In many of these cases it is impossible to decide, without N-labeling experiments, whether the third nitrogen of the triazole ring is derived from the toluene-p-sulfonyl azide or from the activated methylene compound. With amides, amidines, and nitriles, the first possibility seems more reasonable, but with imines, the third nitrogen is that of the imino group (Scheme... 

With a range of methods available for the formation of 1,3-dicarbonyl compounds, the dicarbonyl diazomethanes can be readily prepared via a simple diazo transfer reaction with sulfonyl azide. This has made a vast array of dicarbonyl diazomethanes available, which enhances the versatility in organic synthesis. A selection of examples from recent literature to illustrate the versatility of the cyclopropanation using dicarbonyl diazomethane in the construction of natural products as well as other biologically active compounds is described below. 

The possible mechanism for diazo transfer from p-toluenesulfonyl azide to active methylene compound 3 (flanked by carbonyl groups) is depicted below.1,3 Deprotonation of a-keto ester 3 with NEt3 leads to enolate 4 which attacks at the electrophilic N of the sulfonyl azide 5 to give intermediate tosyl derivative 6. Proton transfer occurs within intermediate 6 followed by elimination of p-toluenesulfonamide, leading to diazo compound 7 and the by-product -toluene sulfonamide 8.1,3... 

A-Sulfonylamidines can be prepared by three-component coupling [31] of alkynes (R = alkyl, aryl or silyl), sulfonyl azide and amine, which is known as click chemistry. [32] The use of alkyl azides in place of sulfonyl azide without a copper catalyst results in the formation of 1,2,3-triazoles (Scheme 3.18). This reaction shows substrate tolerance to each component. Reaction with an optically active amino ester is performed without racemiza-tion. A-Boc-ynamide (R = NPhBoc) can act as the alkyne component in the synthesis of N-Boc-aminoamidines [33]. 

Quinazolinones are an important class of fused heterocycles that have been reported with remarkable activities in biology and pharmacology such as anticancer, antiinflammatory, anticonvulsant, antibacterial, antidiabetic, hypolipidemic, and protein tyrosine kinase inhibitors. Alper and Zheng reported a palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides to produce quinazolin-4(3H)-ones in 2008. A wide variety of substituted quinazolin-4(3H)-ones were prepared in 63-91% yields (Scheme 3.27a). The reaction is believed to proceed via in situ formation of an amidine, followed by oxidative addition, CO insertion, and intramolecular cyclization to give the substituted quinazolin-4(3H)-ones. Later on, a procedure was established based on generating the amidine in situ by a copper-catalyzed reaction of terminal allq nes, sulfonyl azide and o-iodo-anilines. The desired quinazolinones can be produced by carbonylation with Pd(OAc)2-DPPB-NEt3-THF as the reaction system. In the same year, Alper s group developed a procedure for 2,3-dihydro-4(lH)-quinazolinone preparation. The reaction started with the reaction of 2-iodoanilines and N-toluenesulfonyl aldimines followed by palladium-catalyzed intramolecular... 

In 2012, Kim etal. [85] reported the intermolecular amidation of arenes with sulfonyl azides, which is a direct C-H process (Scheme 4.22). A cationic Rh complex was used in air. The application was showcased by the synthesis of 6-arylpurine derivatives, which show antimycobacterial, cytostatic, and anti-HIV activity. The reaction scope was successfully demonstrated. 

A three-component reaction for the synthesis of functionalized benzimidazoles from terminal alkynes, o-aminoanilines, and / -tolylsulfonyl azide is developed by Wang and coworkers (Scheme 8.52). The C(sp)-H bond of alkyne was activated in this reaction via Cul-catalyzed azide-alkyne cycloaddtion (CuAAC) reaction which could lead to the formation of a ketenimine intermediate by the release of N2- The benzimidazoles could be obtained by intramolecular nucleophilic addition and subsequent elimination of amide intermediate with 2% H2SO4 under reflux conditions [91]. They also developed another protocol for the synthesis of substituted benzimidazole derivatives via a sequential three-component cascade reaction from sulfonyl azides, alkynes, and 2-bromoanilines using Cul as catalyst. Similarly, the C-H bond of alkyne was activated at the process of copper-catalyzed azide-alkyne cycloaddtion (CuAAC) reaction [92]. 

The initiator in ATRP is usually a low molecular weight activated organic halide (RX, R=aclivated alkyl, X=chlorine, bromine, iodine). However, organic pscudohalidcs (e.g, X=thiocyanatc, azide) and compounds with weak N-X (e.g. N-bromosuccinimide 7 ) or S-X (e.g. sulfonyl halides - see below) have been used. 

The transformation of an active CH compound into the corresponding diazo derivative with -toluenesulfonyl azide has been designated a diazo transfer reaction and possesses a variety of preparative uses. The method has been useful for the syntheses of diazo derivatives of cyclopentadiene, 1,3-dicar-bonyl compounds, 1,3-disulfonyl compounds,1,3-keto-sulfonyl compounds, ketones, " carboxylic acid esters, and /3-keto imines. Further reaction of these diazo intermediates can lead to azo compounds,"- " 1,2,3-triazoles, and pyrazolinones. ... 

Cyclizations. Annulation accompanies oxidation of A-sulfonyl-4-methoxyanilines with Phl(OCOCp3)2 in the presence of 1-alkenes. 5-Methoxyindoles or indolines are produced in this one-pot reaction. Cyclization of 3-arylpropyl azides where the aromatic ring is activated (e.g., 3-methoxylated) to fused quinone imines is observed. ... 

Chloro- and 2, 6 -dichloro-4-nitrodiphenyl ethers were converted into the corresponding 4 -sulfonyl chlorides by reaction with excess chlorosulfonic acid (five equivalents). " The comparatively poor yields of the sulfonyl chlorides obtained may be due to their susceptibility towards hydrolysis, as a result of the presence of the electron-withdrawing groups. Several sulfonyl derivatives of diphenyl ethers, e.g. azides, hydrazides and hydrazones showed pronounced algaecidal activity. 

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