2- Ethynylpyrroles

Dichloro-1,8-naphthyridine with tert-butyl 2-ethynylpyrrole-l-carboxylate gave 2,7-bis(l-terf-butoxycarbonylpyrrol-2-yl-ethynl)-l,8-naphthyridine (26) [reactants, Et3N, Cul, Pd(PPh3)2Cl2, THF 784].122,cf 118... 

The mechanism of this new ethynylation involves an addition-elimination sequence, probably promoted by the coordinatively unsaturated center (electrophilic assistance) and by mechanoactivation (grinding up the reactants with AI2O3) <2004TL6513, 2006RJ01348>. The intermediates of this reaction, 2-(l-bromo-2-acylethenyl)pyrroles 700, are isolated and converted upon AI2O3 to 2-ethynylpyrroles 699 (Scheme 136) <2006RJ01348>. 

Acyl-l-bromoethenyl)pyrroles 144 were converted with AI2O3 to 2-ethynylpyrroles 143 (Equation (40)) (06RJO1348). 

The reaction is general in character. Apart from 2-ethynyl-4,5,6,7-tetrahydroindoles, 5-aryl-2-ethynylpyrroles and 3-ethynyIindoles also undergo [2+2]-cycloaddition. This is the first example of nonphotochemical [2+2]-cycloaddition of DDQ to the triple bond. The mechanism of the reaction involves one-electron transfer to generate ion-radical pair containing ethynylpyr-role radical cation (detected in the UV spectra of the reaction mixture at -30°C) and DDQ radical anion (identified by ESR). 

Heterocycle 108 was obtained in 45% yield by the reaction of dilithiated A-ethynylpyrrole 110 with elemental tellurium followed by a treatment of the reaction mixture with hexamethylphosphorus triamide [95JOM(493)271]. 

Iodopyrroles, such as the TV-TIPS derivative shown in 6.44. couple equally efficiently. Its reaction with a series of acetylene derivatives in the presence of a regular catalyst gave rise to the TV-protected 3-ethynylpyrrole... 

Pyrolysis of i247 at 700-760°C gave the nitrile 274 in 65% yield together with a mixture comprising three reactive components (Scheme 4). Spectro-metric data suggest a mixture of ethynylpyrrole (275) and two azafulvenes (276 and 277). The formation of the major product is consistent with earlier... 

Extension of the reaction to diacetylene might clear the way to the ethynylpyrroles 114, promising monomers for conducting polymers and building blocks for the synthesis of new heterocycles. It turned out (76ZOR905) that, in an aqueous DMSO in the presence of catalytical amounts of KOH, diacetylene indeed added exothermically to ketoximes to form O-1 -butene-3-viny(ketoximes (113) (Scheme 54). 

It is not clear, for example, why the expected ethynylpyrroles cannot be obtained by use of diacetylene, although the corresponding Z-0-(/3-ethynylvinyl)oximes are formed fairly readily (see Section V.B). 

All these ethynylation reactions are particularly important since the common Sonagashira coupling does not allow ethynylpyrroles with strong electron-withdrawing substituents at the acetylenic fragments to be synthesized (99J(P1)2669). 

A -Lithioethynyl-2-lithiopyrrole, generated by dilithiation of A -ethynylpyrrole 203 with 2 equiv of butyllithium, was treated with either selenium or tellurium followed by addition of a mixture of /-butyl alcohol and hexamethylphos-phoric triamide to give the bicyclic compounds 204 and 205 (Scheme 12) <1995JOM271>. 

The formation of the expected ethynylpyrroles is not also observed in the reaction with diacetylene, though the corresponding Z-O-ethynyl vinyl ketoximes are isolated (Scheme 1.124) [293,294]. Their best yields (36%-41%) are attained when water content in the reaction mixture is 10%-30% and KOH concentration is l%-2%. 

It is also unclear why one fails to prepare the expected ethynylpyrroles using diacetylene, though the corresponding Z-O-(p-ethynylvinyl) oximes are formed easily (see Section 1.3). 

The discussed variants of novel ethynylation of the pyrrole nucleus look even more attractive taking into account that the standard transition metal-catalyzed reactions, including the Sonogashira cross-coupling, do not allow the ethynylpyrroles with electron-withdrawing functions in acetylene substituent to be synthesized [525]. 

Cycloadducts of C-Ethynylpyrroles and Indoles with DDQ and Products of Their Alcoholysis... 

N-Ethynylpyrrole (Table 2.14) is a unique acetylene. In particular, it is a starting product for the synthesis of pyrrolyldiacetylenes, which form polymeric films with promising optical properties. N-Ethynylpyrrole is synthesized from a pyrrole and 1,2-dichloroethene in the system KOH/DMSO (Scheme 2.127) [597]. 

N-Ethynylpyrrole has been prepared [598] by reacting pyrrole with trichloroethene and potassium tert-butoxide in tetrahydrofuran and subsequent dechlorinating the adduct with methyUithium or n-butylUthium in diethyl ether (Schane 2.128). It is assumed that N-(l,2-dichlorovinyl)pyrrole is formed via nucleophilic addition of pyrrole to dichloroacetylene, a product of trichloroethene dehydrochlorination. 

SCHEME 2.127 Synthesis of N-ethynylpyrrole via the reaction of pyrrole with 1,2-dichloroethene in the KOH/DMSO system. 

SCHEME 2.128 Synthesis of N-ethynylpyrrole from pyrrole and trichloroethene. 

The treatment of N-l,2-dichlorovinylpyrrole with two equivalents of n-BuLi leads to N-lithioethynylpyrrole [688], With three equivalents of n-BuLi (THF, -40°C - -35°C), a further lithiation occurs at the a-position of the pyrrole ring to produce 2-lithio-l-(lithioethynyl)pyrrole. The reaction of the latter with trimethylchlorosilane, butyl iodide, and dimethylformamide results in the corresponding ethynylpyrroles (Scheme 2.225, Table 2.20). The same dilithium derivative upon contacting with elemental sulfur, selenium, and tellurium furnishes (t-butanol/DMF, 0°C-35°C) pyrrolo[2,l-( ][l,3]thiazole, pyrrolo[2,l-fc][l,3]selenazole, and pyrrolo[2,l-( ][l,3] tellurazole, respectively (Table 2.20) [688]. 

SCHEME 2.225 Lithiation of N-ethynylpyrrole and synthetic application of the dianion formed. 

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