Halogen-metal Exchange Reaction Research Articles

A convenient Synthesis of 6-Substituted-2,2-Dimethyl-2H-1-Benzopyrans

Abstract Various 2,2-dimethyl-6-functional-2H-1-benzopyrans were prepared via a halogen-metal exchange reaction followed by treatment with electrophiles. These 6-functionalized chromenes are important synthetic intermediates for preparation of benzopyran-based potassium channel openers.

新規な安定ＰＧＩ２誘導体ｍ‐フェニレンＰＧＩ２の合成研究 ベラプロストナトリウムの製造法開発

Just after the discovery of PGI2, we started to find chemically and metabolically stable PGI2 derivatives with longer duration of action. Extensive studies led us to a new class of stable PGI2 analogue, 5, 6, 7-trinor-4, 8-inter-m-phenylenePGI2 that has a phenol moiety instead of enol-ether linkage in PGI2. In order to accomplish synthesis of the m-phenylenePGI2, novel synthetic methods were developed, for instance, ortho-selective metal-halogen exchange reaction of bromoanisoles by means of Grignard reagent, copper-catalyzed SN2' cyclization to prepare dihydrocyclopenta [b] benzofuran, and regioselective and stereo-selective elongation of ω-side chain by Prins reaction. Further efforts were devoted to synthesize derivatives of m-phenylenePGI2 with enhanced pharmacological activity and less adverse reaction. Finally, we attained to Beraprost sodium which is the first launched drug as an orally active PGI2. This paper will focus on the study of total syntheses of m-phenylenePGI2.

Synthesis, Lipophilicity, and Stability of Tetrakis (pentafluorophenyl) borate (FTPB) Anion under Highly Acidic Conditions in Comparison with Those of Tetrakis (3,5-bis (trifluoromethyl) phenyl) borate (TFPB) Anion

An improved synthetic method for tetramethylammonium FTPB by a metal-halogen exchange reaction of pentafluorophenyl bromide with magnesium in the presence of a catalytic amount of butyl bromide and by a subsequent reaction with boron trifluoride diethyl ether was developed. The lipophilicity of tetramethylammonium FTPB in a range of hydrophobic organic solvents and its stability under highly acidic conditions were investigated in comparison with those of tetramethylammonium TFPB.

Coordination chemistry of perhalogenated cyclopentadienes and alkynes: XVIII. Mechanistic studies on the metal-halogen exchange reaction of ring-halogenated metallocenes: The influence of stoichiometry, temperature, solvent and reaction time

When [C 5Br 5]Mn(CO) 3 ( 1) is treated with butyllithium and hydrolysed after some time, one can always obtain more than one product, independent of stoichiometry, solvent, temperature and lithiation time. However, the distribution of products strongly depends on the reaction conditions. For example, in THF, with a tenfold excess of butyllithium at −78°C, a conversion of more than 80% into [C 5H 5]Mn(CO) 3 can be achieved. In IC 5 Cl 4Br]Mn(CO) 3 ( 2) only a maximum of two halogens can be substituted by hydrogen. These results can be explained in terms of the competition between butyl lithium and the lithiated species [C 5X 4Li]Mn(CO) 3 in the halogen-metal exchange reaction.

Boron-Activation of Acetylenes to Nucleophilic Addition Reactions

Nucleophilic carbon centers formed through metal-halogen exchange reactions have been found to undergo rapid intramolecular addition reactions with boron-activated acetylenes giving 4- and 5-membered cyclic boron-stabilized vinyl anions which may be trapped with electrophiles. Adducts of these anions with aldehydes fail to undergo the boron-Wittig reaction, but instead undergo acid-catalyzed dehydration to dimesitylboryl-substituted dienes

Stereoselective construction of functionalized bicyclic carbocycles through metal-halogen exchange-initiated sequential conjugate addition reactions

Rapid metal-halogen exchange reactions have been used to initiate the stereoselective formation of transbicyclo[4.3.0]nonane and strained trans-bicyclo[3.3.0]octane derivatives through sequential intramolecular conjugate addition reactions. Stereoselectivity has been controlled in anionic olefin addition reactions as well as in corresponding radical cyclizations through control of acceptor olefin stereochemistry.

Isolation and structural characterization of unsolvated lithium aryls

The synthesis and characterization of three examples of unsolvated lithium aryls are described. The compounds (Li(Trip)} 4 (1, Trip=2,4,6-i-Pr 3 C 6 H 2 ), (Li(2,6-Mes 2 C 6 H 3 )} 2 (2, Mes= 2,4,6-Me 3 C 6 H 2 ), (Li(n-Bu)) 2 (LiMes * ) 2 (3), and (Li(n-Bu)} 2 (LiMes * ) 2 -Mes * Br(3-Mes * Br, Mes * =2,4,6-t-Bu 3 C 6 H 2 ) were synthesized by a metal-halogen exchange reaction between n-butyllithium and the appropriate aryl bromide (1 and 3) or iodide (2). The X-ray crystal structures of 1 and 3 show that they are tetrametallic lithium species involving almost planar arrays of four lithium atoms

Reactions of triorganostannyl ions with haloarenes in liquid ammonia. Competition between halogen-metal exchange and electron-transfer reactions

The reactions between triorganostannyl ions and haloarenes in liquid ammonia can lead to substitution and to reduction products. It was found that, depending on the structure of the tin nucleophile, the halogens involved, the structure of the haloarene, and the experimental conditions, the reactions can follow exclusively either an S RN 1 mechanism (substitution products), or a halogen-metal exchange (HME) mechanism (dehalogenation-reduction products) and that a competition between both mechanisms (mixture of substitution and reduction products) is also possible

Unusual metalation and halogen-metal exchange reactions between 1,3-xylyl crown ethers and organomagnesium reagents. X-ray structure of 2-[(p-tert-butylphenyl)magnesio]-1,3-xylylene-18-crown-5. [Erratum to document cited in CA115(21):232313a

Unusual metalation and halogen-metal exchange reactions between 1,3-xylyl crown ethers and organomagnesium reagents. X-ray structure of 2-[(p-tert-butylphenyl)magnesio]-1,3-xylylene-18-crown-5. [Erratum to document cited in CA115(21):232313a

Bromine addition to α-(1-hydroxyalkyl)- and α-(1-alkoxy-alkyl)-α,β-unsaturated esters: an approach to hydroxyfimbrolide and bromobeckerelide

Conventional ionic bromination of electron-poor olefins, 2-(1-hydroxyalkyl)- and 2-(1-alkoxyalkyl)propenoates, 2b-d, and methyl ( E)-2-(1-hydroxyethyl)-2-butenoate, 3a, proceeds with yields higher than 80%. Treatment of ( E)-3-bromo-2-[1-[(2-methoxyethoxy)methoxy]butyl]propenoic acid, 16, with two equivalents of strong bases, reaction related with a possible hydroxyfimbrolide and bromobeckerelide synthesis, resulted in the halogen-metal exchange reaction affording the acrylic acid 18, presumably through the generation of dianion 19.

Unusual metalation and halogen-metal exchange reactions between 1,3-xylyl crown ethers and organomagnesium reagents. X-ray structure of 2-[(p-tert-butylphenyl)magnesio]-1,3-xylylene-18-crown-5

Unusual metalation and halogen-metal exchange reactions between 1,3-xylyl crown ethers and organomagnesium reagents. X-ray structure of 2-[(p-tert-butylphenyl)magnesio]-1,3-xylylene-18-crown-5

Metal-halogen exchange reactions of 1,5-diiodonaphthalene. Synthesis of 1,5-disubstituted naphthalene derivatives

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetal-halogen exchange reactions of 1,5-diiodonaphthalene. Synthesis of 1,5-disubstituted naphthalene derivativesWuyi Wang, Stan V. D'Andrea, Jeremiah P. Freeman, and Jacob SzmuszkoviczCite this: J. Org. Chem. 1991, 56, 8, 2914–2915Publication Date (Print):April 1, 1991Publication History Published online1 May 2002Published inissue 1 April 1991https://doi.org/10.1021/jo00008a059RIGHTS & PERMISSIONSArticle Views310Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (299 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Triazolo[4,5-d]pyrimidines. XI. Halogen-Metal Exchange Reaction of 5-Halo-3H-1,2,3-triazolo-[4,5-d]pyrimidines with Butyllithium.

The amino group at the 7-position on the 3H-1, 2, 3-triazolo[4, 5-d]pyrimidine ring was converted into halogen atoms by treatment with isopentyl nitrite in halomethanes, in satisfactory yields. The halogen-metal exchange reaction between 7-iodo-3-phenyl-3H-1, 2, 3-triazolo[4, 5-d]pyrimidine (2) and butyllithium in the presence of N, N, N', N'-tetramethylethylenediamine proceeded, giving the 7-lithio compound (9). The lithio compound (9) reacted smoothly with electrophiles to give the corresponding 7-substituted compounds (15-18). On the other hand, the reaction of 7-chloro-3-phenyl-3H-1, 2, 3-triazolo[4, 5-d]pyrimidine (1) with butyllithium gave the ring fission product, 5-amino-1-phenyl-1H-1, 2, 3-triazole-4-carbonitrile (14).

Organo-lithiation and halogen metal exchange reactions in organic synthesis-an anomolous aromatic substitution via halogen-metal exchange

Synthesis via organo-lithium compounds is reviewed. An anomalous aromatic substitution via halogen-metal exchange is described. Here, the substitution does not occur at the position where the halogen was present; but at an alternate position. A mechanism is advanced, in which the halogen-metal exchange is proposed as being faster than the hydrogen(acidic)-metal exchange.

ChemInform Abstract: Azoles. Part 5. Metal‐Halogen Exchange Reactions of Polybromoimidazoles.

ChemInformVolume 18, Issue 44 Heterocyclic Compounds ChemInform Abstract: Azoles. Part 5. Metal-Halogen Exchange Reactions of Polybromoimidazoles. B. IDDON, B. IDDON Ramage Lab., Dep. Chem. Appl. Chem., Univ. Salford, Salford M5 4WT, UKSearch for more papers by this authorN. KHAN, N. KHAN Ramage Lab., Dep. Chem. Appl. Chem., Univ. Salford, Salford M5 4WT, UKSearch for more papers by this author B. IDDON, B. IDDON Ramage Lab., Dep. Chem. Appl. Chem., Univ. Salford, Salford M5 4WT, UKSearch for more papers by this authorN. KHAN, N. KHAN Ramage Lab., Dep. Chem. Appl. Chem., Univ. Salford, Salford M5 4WT, UKSearch for more papers by this author First published: November 3, 1987 https://doi.org/10.1002/chin.198744187Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume18, Issue44November 3, 1987 RelatedInformation

ChemInform Abstract: Reaction of 2,4,6‐Tri‐tert‐butylphenyllithium with Bromotrichlorosilane. Generation of Trichlorosilyllithium, LiSiCl3.

AbstractTrichlorosilyllithium (III) is obtained by reacting bromotrichlorosilane (I) with sufficiently sterically hindered organolithium derivatives such as (IIa) and (IIb) in a metal halogen exchange reaction.

Regiospecific synthesis of aromatic compounds via organometallic intermediates. Part 5. Substituted perfluoroalkylether benzenes

A new organometallic species, 3,5-Li 2C 6H 3X where X = C 2F 5- (OCF 2CF 2) 4OCF 2CF 2-(IIIa) has been prepared from the corresponding dibromo compound by a metal-halogen exchange reaction. The reactions between IIIa and various substrates were examined in order to determine the usefulness of this diorganometallic reagent as a synthon.

Synthesis and reactions of a perfluoroalkylether Grignard reagent containing a functional ester group

Abstract The first perfluoroalkylether magnesium bromide containing a functional ester group, ROC(O) (CF2)4OCF2CF2MgBr(I) has been synthesized through the metal-halogen exchange reaction between a perfluoroalkylether iodide ester and ethylmagnesium bromide. The thermal stability in diethyl ether of the Grignard reagent and the products of the Grignard's intermolecular reaction at higher temperatures have been established. Reactions of the Grignard reagent with various substrates such as water, diethyl oxalate, ethyl formate, diethyl carbonate, ethyl acetate, ethyl benzoate and ethyl trifluoroacetate indicate the synthetic utility of this Grignard reagent.

A new synthesis of 4-amino-2-quinolinones

Addition of Grignard or organolithium reagents to N -(α-haloacyl)- N -alkylsubstituted anthranilonitriles (e.g. N -(2-bromopropionyl)- N -methyl-2-cyanoaniline) induced anion formation followed by cyclization to 4-amino-2-quinolinones (e.g. 4-amino-1,3-dimethyl-2-quinolinone ( 10 )). Substrates lacking α-hydrogen atoms, such as N -(α-bromoisobutyryl)-2-cyanoaniline, also yielded 3,3-diaethylquinolinedione ( 9b ) by cyclization. In these cases the initial step is a halogen-metal exchange reaction.

Organometallics from some fluorohalocompounds

Readily available fluorohaloethanes of the general formula CF 3CXYZ (X,Y = F,Cl,Br; Z = Cl,Br) were found to be versatile synthetic intermediates for introducing a fluoro- or fluorohaloethyl group into organic molecules via organometallic compounds of magnesium and zinc. The low temperature metal-halogen exchange reaction of the ethanes with alkyl- or aryl-magnesium halides affords Grignard reagents CF 3CXYMgHal which react with aldehydes and ketones to give alcohols. The Grignard compounds failed to react with acid derivatives and their carboxylation by carbon dioxide gave only poor yields of the acids. The carboxylic acids CF 3CXYCO 2H were easily prepared by the reaction of the ethanes CF 3CXYZ with zinc and carbon dioxide under atmospheric pressure. The yields of carboxylation were substantially enhanced by the application of ultrasound. The chlorine- and bromine-containing acids were smoothly reduced to fluoropropionic acids CF 3CFHCO 2H and CF 3CH 2CO 2H.