Alkynes haloalkynes

Cis-olefins or cis./rjns-dienes can be obtained from alkynes in similar reaction sequences. The alkyne is first hydroborated and then treated with alkaline iodine. If the other substituents on boron are alkyl groups, a cis-olefin is formed (G. Zweifel, 1967). If they are cir-alkenyls, a cis, trans-diene results. The reactions are thought to be iodine-assisted migrations of the cis-alkenyl group followed by (rans-deiodoboronation (G. Zweifel, 1968). Trans, trans-dienes are made from haloalkynes and alkynes. These compounds are added one after the other to thexylborane. The alkenyl(l-haloalkenyl)thexylboranes are converted with sodium methoxide into trans, trans-dienes (E. Negishi, 1973). The thexyl group does not migrate. 

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. 

Haloalkynes (R—C=C—X) react with ArSnBu3 and Cul to give R—C= C—Ar. Acetylene reacts with two equivalents of iodobenzene, in the presence of a palladium catalyst and Cul, to give 1,2-diphenylethyne. 1-Trialkylsilyl alkynes react with 1-haloalkynes, in the presence of a CuCl catalyst, to give diynes and with aryl triflates to give 1-aryl alkynes. Alkynes couple with alkyl halides in the presence of Sml2/Sm. Alkynes react with hypervalent iodine compounds " and with reactive alkanes such as adamantane in the presence of AIBN. ... 

Aminocarbonylation has been combined with the Pauson-Khand reaction to construct fused tricyclic alkaloid skeletons (see 00154). The tandem aminocarbonylation/Pauson-Khand reaction of haloalkynes with a chiral allylic amine promoted by Co2(CO)8 gave angular triquinanes as exemplified in Scheme 25. Thus, the reaction of l-chloro-2-phenylethyne 175 with Co2(CO)8 at 0°C gave alkyne-dicobalt complex 176, which was converted to enoyl-dicobalt complex 177 upon warming to 25 °C. The reaction of enoyl-dicobalt complex 177 with cyclopente-nylmethyl(l-phenylethyl)amine 179 yielded Pauson-Khand reaction product, angular triquinane 180, via A -allylic aminocarbonylated alkyne-dicobalt complex 178 (Scheme 25). ... 

Whereas Glaser-type oxidative coupling opens efficient synthetic pathways toward symmetrical diynes, its performance in heterocoupling is poor. The latter may be accomplished by Cadiot-Chodkiewicz coupling of terminal alkynes with 1-haloalkynes (usually 1-bromoalkynes). The reaction is conducted in the presence of an amine and catalytic amounts of a copper(I) salt. Because, in contrast with the Glaser-type reactions described above, it follows a nonoxidative reaction mechanism, oxygen is not necessary - but needs often not to be excluded (Scheme 4) [9]. 

As already mentioned, there have been few mechanistic examinations of the copper-catalyzed Cadiot-Chodkiewicz heterocoupling reaction. Kinetic studies with the less reactive chloroalkynes [11a] have led to the assumption, shown in Scheme 7, that coupling between alkynes and haloalkynes proceeds through initial formation of copper(I) acetylides, probably formed by an acetylenic activation process similar to that described above for oxidative homocouplings. Subsequently, two reaction pathways may be reasonable ... 

Nonoxidative Heterocoupling of Terminal Alkynes with Haloalkynes Cadiot-Chodkiewicz Reaction... 

The radical intermediates from Cr(II) reduction of alkyl halides can in principle be used synthetically, but have only seen limited attention to this point. co-Haloalkynes (bromides, iodides), in the presence of excess Cr(C104)2, undergo cyclization reactions to form exo-alkylidene cycloalkanes (equation 176)347. These reactions proceed by the radical cyclization of intermediate 42 onto the alkyne unit, which undergoes subsequent reduction by Cr(II) to give a hydrolytically unstable vinylchromium(III). Rings of four, five and six members can be formed. Alternatively, a-iodo esters undergo intramolecular atom transfer radical cyclizations onto alkynes or alkenes with catalytic or stoichiometric amounts of... 

More often such bromo- and iodoalkynes are employed with another synthetic goal in mind, namely, in the Cadiot-Chodkiewicz reaction for the formation of symmetric or asymmetric 1,3-diynes by reaction of the haloalkyne with a terminal alkyne (Figure 13.25). Additional reagents essential for the success of this reaction are one equivalent or more of an amine and a substoichiometric amount of Cul. As with the Cacchi and Stephens-Castro coupling reactions of Section 13.3.4, a Cu-acetylide is the reactive species in the Cadiot-Chodkiewicz coupling. It is formed in step 1 of the mechanism illustrated in Figure 13.25. 

The chemistry of haloalkynes with low-valent metal complexes has been reviewed.142 Two competing reactions of anionic metal carbonyls [M(CO) ] with halo-alkynes are (i) abstraction of X+ to give MX(CO) and (ii) nucleophilic displacement of X- to give M(C=CX)(CO) and M(CO) 2(ji-C=C). A recent study of reactions of haloalkynes with [M(CO)3Cp ]- (M = Cr, Mo, W Cp = Cp, Cp )] has clarified the reaction conditions, which are determined by the nucleophilicity of the anionic metal carbonyl and the electron-withdrawing power of any substituent on the C=C triple bond. Cross-coupling of the anion with a chloroalkyne is catalyzed by palladium.143... 

Allylic zirconocenes, generated by hydrozirconation (see Hydrozirconation) of allenic systems, react with terminal alkynes when activated with MAO to regioselectively afford 1,4-dienes. The same MAO catalyzed process, applied to haloalkynes, leads to excellent yields of the 1,4-enyne (100) (Scheme 23). ... 

A listing of alkyne-nucleophile systems whose substitution kinetics have been studied is given in Table 24 for each of these systems. Rate constants and enthalpies and entropies of activation, if available, are tabulated. In order to compare the reactivity of haloalkynes with other organic halides we have also included in Table 24 related rate data for vinylic, aromatic and alkyl halides. 

Using ( )-methylalkenylalanes 140, obtained by highly stereo- and regioselective Zr-catalyzed carboalumination of alkynes, the stereochemically defined enynes 141 can also by synthesized by Pd-catalyzed cross-coupling reactions with 1-haloalkynes [Eq. (47)] [68]. 

Some of the most useful synthetic transformations of terminal alkynes involve intermolecular and intramolecular homo- and cross-coupling reactions between their. sp-carbon centers, leading to butadiyne or polyyne derivatives. The two most widely used and practical systems are (i) oxidative homocoupling reactions, i.e. Glaser and Eglington reactions and (ii) heterocoupling reactions, i.e. Chodkiewicz-Cadiot coupling of a terminal alkyne with a haloalkyne. 

Diels-Alder reactions. The reagent undergoes [4-i-2]cycloadditions to give adducts bearing an alkenylstannane moiety. Accordingly, it can be considered as a synthetic equivalent for acetylene and substituted alkynes (aryl, acyl, and haloalkynes). 

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