Vinyl halides acetylenes

Treatment of vinyl halides with strong base gives acetylenes. 

Unsymmetrical trans vinyl halides have been prepared from acetylenic alcohols by Corey and co-workers (as illustrated in the accompanying formulation) in connection with their synthesis of farnesol and Gecropia juvenile hormone. Several syntheses of vinyl halides (with... 

Simple reaction occurs with aryl halides only when the ring is sufficiently substituted with electron-withdrawing functions to allow attack by the nucleophilic phosphorus.53-56 Generally, reaction with aryl halides requires the presence of a Lewis acid catalyst or some other means of reaction initiation. These reactions will be considered in detail in Chapter 6 of this work. Interestingly, while reactions involving vinylic halides seem to correlate with those of aromatic halides (see Chapter 6), acetylenic halides undergo facile reaction with these phosphorus reagents.57 58... 

A photoinitiated reaction has been reported of trialkyl phosphite with an electron-deficient vinylic halide for which an olefinic carbon is covalently bound to a metallic center (Figure 6.24).92 Unfortunately, only low yields of the target phosphonate are obtained. In another report involving a transition metal bound to carbon, an acetylenic carbon covalently bound to an iron center has been found to undergo... 

General synthesis of pyrroles and 1-vinylpyrroles by the reaction of ketoximes with acetylenes and their synthetic equivalents (vinyl halides and dihaloethanes) in the presence of the strongly basic KOH/DMSO system (Trofimov reaction) has been reviewed ° in recent years. Therefore, in the present work this reaction will be described very shortly. In principle, pyrrole (51) synthesis can be carried out as a one-pot procedure by treating ketones (49) with hydroxylamine and then reacting the ketoximes (50) formed with acetylenes (equation 22). 

Related methodology has been utilized to prepare fluoroenynes either by coupling fluorinated vinyl halides with an acetylenic zinc reagent or via coupling of a fluorinated vinylzinc reagent with l-iodo-l-alkynes2,11, as illustrated in equations 17-21. 

Acetylenic ketones.3 PdCl2(dppf) is generally the most satisractory catalyst for synthesis of acetylenic ketones by carbonylation of aryl and vinyl halides in the presence of a terminal acetylene. 

Alkynes. Because of their less nucleophilic character, alkynes react less readily with hydrogen halides than do alkenes and often require the use a metal halide catalyst. Vinyl halides are formed in the reaction with one equivalent of HHlg. They may react further in an excess of the reagent to yield geminal dihalides. High yields of these compounds can be achieved. The addition of HC1 to acetylene was studied in detail because of the practical importance of the product vinyl chloride (see Section 6.2.4). 

The acetylene substitution reaction proceeds much more rapidly than the related olefin reaction. The acetylene products and starting materials also undergo side reactions such as polymerization concurrently with the substitution. The best yields are obtained when the reactants are diluted with a large excess of amine, or carried out at lower temperatures in methanol with sodium methoxide as the base. Vinylacetylene derivatives can also be prepared by this reaction starting with vinylic halides. For example, ( )-methyl 3-bromo-2-methylpropenoate and r-butylacetylene react in 2 hours at 100° to form the expected vinylacetylene derivative in 59% yield ... 

Under these reaction conditions, nitriles can readily transform to the salts of the corresponding carboxylic acids. This may account for the loss of ketoxime without visible signs of resinification occasionally observed in the synthesis of pyrroles from ketoximes and acetylene or its equivalents, i.e., vinyl halides and dihaloethanes (see Section V.B). 

In the preparation of pyrroles and N-vinylpyrroles from ketoximes, along with vinyl halides, dihaloalkanes as acetylene equivalents can also be used. Pyrroles and /V-vinylpyrroles are formed in a yield of about 30% in the reaction of ketoximes with dihaloalkanes in the presence of excess alkali metal hydroxide in DMSO (Scheme 60) (79IZV2840). 

Before discussing examples of the reactions, it should be pointed out that most types of vinylic halides used in this reaction are easily available. The UV-catalyzed addition of HBr to terminal acetylenes forms the 1-bromo-l-alkenes. The cis isomer is formed almost exclusively if the addition is carried out at dry ice temperature. The 2-bromo or 2-iodo-l-alkenes are obtained from reacting aqueous hydrogen halides with alkynes. The 2-substituted-1-bromo-l-alkenes are available by the bromination-base dehydrobromination reactions. 

An unprecedented halodephosphorylation of o ,/3-acetylenic and a,/3-ethylenic phos-phonic acid monoesters (27) and (29) with (biscollidine)bromine(I) or (biscollidine) iodine(I) hexafluorophosphate, leading to alkynyl (28) and vinyl halides (30), respectively, has been reported.42... 

Vinyl halides are so inert that none has been converted to a fluoride by halogen exchange. Vinyl fluorides have been synthesized from saturated polyhalides by dehalogenation with zinc and by dehydrohalo- genation with alcoholic alkali, and from acetylene by addition of one molecule of hydrogen fluoride.12 18... 

The Sonogashira cross-coupling reaction of terminal acetylenes with aryl or vinyl halides is a powerful tool for generation of carbon-carbon bonds between sp2- and sp-carbon. Numerous molecules of interest can be generated from a wide variety of aryl or vinyl halides (Scheme 3) [18-23],... 

The place of an acetylene in these reactions may be taken by an olefin substituted by a group capable of elimination during the reaction. Thus, aliphatic diazo compounds and vinyl halides give pyrazoles,473 whereas diazomethahe and /J-chlorovinyl ketones give... 

This is an indirect method to obtain an anti Markovnikov addition of HI to terminal acetylenes. Chlorination929 and bromination930 (with bromine or with sodium bromide931) of vinylboronic acids results in inverted vinyl halides. This allows the three-step stereospecific inversion of ( )vinyl bromide into the [Z] isomer (equation 137)932. 

Acetylenic zinc reagents are readily accessible from 1-alkynes by a deprotonation-transmetallation sequence, and consequently have been successfully used to couple with vinyl halides in many cases (see equation 81), including butadiynyl ones161. Among these, coupling reactions with vinyl bromides have been used in the stereoselective synthesis of enediynes and applied to the synthesis of trienic natural products162. 

In the presence of anhydrous Cr(II) halide salts, organic halides undergo one-electron reduction to form radical species, which in the presence of a second equivalent of Cr(II) undergo a second one-electron reduction to form organochromium(III) species (Scheme 5)331. This process works well for allyl, vinyl and acetylenic halides, but not for simple alkyl cases. Alkylchromium(III) species can be formed readily, however, in the presence of catalytic amounts of vitamin B12 or cobalt phthalocyanine (CoPc)332. 

Relevant mechanistic studies of electrophilic additions to acetylene derivatives and the first demonstration of a unimolecular solvolysis of vinyl halides (Grob and Cseh, 1964) stimulated a still growing interest in the field of vinyl cations. 

Perfluoroalkynylcopper reagents can be prepared by metathesis reactions with the zinc or cadmium reagent (e.g., formation of 6) or by treatment of terminal (perfluoroalkyl)acetylenes with copper(I) chloride/ammonium hydroxide.69 Perfluoroalkynylcopper reagents react with aryl (e.g., formation of 7) and vinyl halides as well as undergoing oxidative dimerization reactions upon exposure to air.2... 

The mechanism and stereochemsitry of dehydrohalogenations from vinyl halides have been extensively reviewed - It should however be pointed out that the effects of particular bases and solvents and of temperature cannot always be predicted with confidence as to rate of reaction and product distribution (acetylene, allene, diene). Therefore a variety of combinations of base, solvent and reaction conditions should be tried in order to obtain satisfactory results. 

Dehydrohalogenation by oxygen bases from vinyl halides proceeds readily by trans elimination via an 2-type of mechanism. c/s-Elimination is sluggish or does not occur at all. Thus trans elimination from bromovinyl ethers 2 (R = alkyl) furnishes the acetylenes 3 in a fast reaction in about 90% yield, whereas elimination from 4 (R = alkyl) is very sluggish and yields a mixture of the acetylene 3 and allene 5 (equations 17 and 18). Similar observations were shown in Schemes 1 and... 

The acetylide so formed can be directly alkylated to an internal acetylene without work-up. A further advantage of dehydrohalogenation of vinyl halides with NaNH in liquid ammonia or in a dipolar aprotic solvent (e.g. DMSO) is that both the cis and trans haloolehns furnish the acetylene, in contrast to reaction with oxygen bases (see Section II.A.2, equation 19). Bromoolefins 9 and cis-10 are converted to... 

Organolithium compounds RLi (R = Me, Et, //-Bu, Ph) are excellent dehydrohalo-genating agents of vinyl halides in ether or THE solution under very mild conditions at temperatures below 0 °C. In a first step the acidic geminal hydrogen is replaced by lithium in a slow step to give an alkenyllithium which can be isolated at low temperature. In a second fast step lithium halide is eliminated to furnish an acetylene (equation 61). Two equivalents of alkyllithium are needed according to this equation. 

The unstable acetylene 11 is obtained by dehydrohalogenation of the appropriate vinyl halide with BuLi (equation 62) . A series of mono- and dihaloacetylenes are similarly obtained in low to moderate yields on using PhLi in ether at 0 °C (e.g. 

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