Halides, vinyl reaction with alkynes

The coupling of alkenylboranes with alkenyl halides is particularly useful for the stereoselective synthesis of conjugated dienes of the four possible double bond isomers[499]. The E and Z forms of vinylboron compounds can be prepared by hydroboration of alkynes and haloalkynes, and their reaction with ( ) or (Z)-vinyl iodides or bromides proceeds without isomerization, and the conjugated dienes of four possible isomeric forms can be prepared in high purity. 

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

Vinylic halides can react by a SrnI mechanism (p. 855) in some cases. An example is the FeCl2 catalyzed reaction of l-bromo-2-phenylethene and the enolate anion of pinacolone (t-BuCOCH2 ), which gave a low yield of substitution products along with alkynes. ... 

Palladium-catalyzed reaction of alkyne 47 with a variety of aryl and vinyl halides afforded alkenes 48 in good yield. Cyclization to quinolines 49 was performed by treating 4 8 with TsOH in EtOH <96T(52)10225>. 

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). 

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. 

This coupling of terminal alkynes with aryl or vinyl halides is performed with a palladium catalyst, a copper(I) cocatalyst, and an amine base. Typically, the reaction requires anhydrous and anaerobic conditions, but newer procedures have been developed where these restrictions are not important. 

Representatives of the little-known class of silicon-copper compounds are formed in situ from organosilyllithium compounds and Cud) halides or pseudohalides they can then undergo cleavage at the Si-Cu bond with alkynes (entries 123 and 124). The reaction, particularly with (R3Si)2CuLi, is regiospecific, and a route to useful vinyl derivatives. 

The reaction sequence in the vinylation of aromatic halides and vinyl halides, i.e. the Heck reaction, is oxidative addition of the alkyl halide to a zerovalent palladium complex, then insertion of an alkene and completed by /3-hydride elimination and HX elimination. Initially though, C-H activation of a C-H alkene bond had also been taken into consideration. Although the Heck reaction reduces the formation of salt by-products by half compared with cross-coupling reactions, salts are still formed in stoichiometric amounts. Further reduction of salt production by a proper choice of aryl precursors has been reported (Chapter III.2.1) [1]. In these examples aromatic carboxylic anhydrides were used instead of halides and the co-produced acid can be recycled and one molecule of carbon monoxide is sacrificed. Catalytic activation of aromatic C-H bonds and subsequent insertion of alkenes leads to new C-C bond formation without production of halide salt byproducts, as shown in Scheme 1. When the hydroarylation reaction is performed with alkynes one obtains arylalkenes, the products of the Heck reaction, which now are synthesized without the co-production of salts. No reoxidation of the metal is required, because palladium(II) is regenerated. 

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. 

The hydrozirconation of alkynes is a well-established reaction, giving vinylic zirconium species of known regio-and stereochemistry.176 These species react with aryltellurium halides leading to vinylic tellurides with the ( )-stereochemistry 98 (Scheme 61),177,178 so complementing the other general routes to these compounds which give preferentially the (Z)-products (Sections 9.13.5.2.3, 9.13.5.2.5). 

The intramolecular reaction can be extended to the cross-annulation reaction of aryl halides with unsaturated compounds [31,33]. For example, 2-halo-biphenyls react with alkynes to give phenanthrene derivatives [96,97]. By using the method, the analogs of hypericin known as antiviral agent (Eq. 45) [98] and indolocarbazoles (Eq. 46) [99] have been prepared. In these reactions, vinyl-palladium intermediates are involved. 

The reaction was applied to the formation of arylcopper used for homocoupling and coupling reactions, which have already been described in Section IV.B.2. In addition, it was established that the simple use of copper(I) salts in polar solvents permitted the transmetallation from tin to copper. The transient vinylcopper reagent was subjected to various intramolecular reactions such as coupling with vinyl halides , addition to a, /S-unsaturated ketones , to a, /3-unsaturated esters and addition to a, /3-alkynic esters . In addition to copper(I) halides, the reaction can be mediated by copper(I) cyanide and... 

Lewis acid-catalyzed reactions of readily ionizable alkyl halides with alkynes yield vinyl halides [207]. The regioselectivities of these additions can be rationalized by the relative stabilities of the intermediate vinyl cations. Unlike the situation described for additions to alkenes, there is no preference for anti-additions, and the stereoselectivities can be explained by the intermediacy of nonbridged species [208]. The site of nu-... 

Water-soluble palladium(O) complexes have also been used as homogeneous catalysts in aqueous-solution alkylation reactions. The particular complex that has been used is Pd(TPPMS>3. Aryl or heteroaromatic halides can be coupled with aryl or vinyl boronic acids, alkynes, alkenes, or dialkyl phosphites with this palladium(0) complex. This complex in aqueous solution can also be used for the coupling of alkynes with unprotected iodonucleotides, iodonucleosides, and iodoamino acids (133). 

Reaction with an amine, AIBN, CO and a tetraalkyltin catalyst also leads to an amide.Benzylic and allylic halides were converted to carboxylic acids electroca-talytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions.Allylic (9-phosphates were converted to allylic amides with CO and ClTi=NTMS, in the presence of a palladium catalyst. Terminal alkynes were converted to the alkynyl ester using CO, PdBr2, CuBr2 in methanol and sodium bicarbonate. ... 

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