Alkenyl halides terminal alkynes

Hydrosilylation-halodesilylation sequence can be used for the stereoselective preparation of synthetically useful alkenyl halides from alkynes (180-183). The combination of the platinum-catalyzed hydrosilylation of terminal alkynes and the chloro- or bromodesilylation of the resulting ( )-alkenylsilanes gives substituted 1-haloalkenes (Scheme 26). 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

The alkenylzirconium 685, prepared by hydrozirconation of a terminal alkyne with hydrozirconocene chloride, reacts with alkenyl halide to afford the conjugated diene 686(545]. The Zr reagent can be used even in the presence of the carbonyl group in 687, which is sensitive to Al and Mg reagents. 

The cis thioboration of terminal alkynes with 9-(arylthio)-9-BBN is catalyzed by Pd(Pli3P)4 in the presence of styrene. The product 136 is converted into the vinyl sulfides 137 and 138 by the treatment with MeOH or by Pd-catalyzed cross-coupling with aryl or alkenyl halides using K3PO4 in DMF[68]. No thioboration takes place with internal alkynes. 

The coupling of terminal alkynes with aryl or alkenyl halides catalysed by palladium and a copper co-catalyst in a basic medium is known as the Sonogashira reaction. A Cu(I)-acetylide complex is formed in situ and transmetallates to the Pd(II) complex obtained after oxidative addition of the halide. Through a reductive elimination pathway the reaction delivers substituted alkynes as products. 

In contrast to the (E)-isomer, (Z)-alkenyl(phenyl)-A3-iodane 41 is labile and decomposes with a half-life time of 20 min to terminal alkynes in chloroform solution at room temperature [64]. Stereo electronically preferable reductive anti / -elimination accounts for this facile decomposition. In fact, the kinetic results for E2-type dehydrohalogenation of vinyl halides show that the relative rates of elimination decrease in the order anti /3->syn / - a-elimination [65]. Similar anti -elimination of vinyl-A3-iodane was proposed in the oxidation of methoxyallene with (diacetoxyiodo)benzene 4 to 3-acetoxy-3-methoxypropyne [66]. 

In addition to coupling via Cu acetylides generated in situ as mentioned above, the coupling of terminal alkynes has been carried out smoothly using actylides of Zn and other metals as an alternative method of arylation and alkenylation of alkynes [66]. Sn[67], Zn[68] and Mg[69] acetylides are used frequently as activated alkynes, rather than the alkynes themselves, and their reaction with halides proceeds without using Cul. 

Terminal alkynes 170 undergo the substitution with aryl and alkenyl halides to form arylalkynes and enynes in the presence of Cul, as described in Section 3.3.1. However, the insertion of terminal alkynes 170 occurs in the absence of Cul, and the alkenylpalladium complex 171 is formed as an intermediate, which cannot be terminated by itself and must undergo further reactions, such as alkene insertion or anion capture. These reactions of terminal and internal alkynes with intermediates 172 and 173 are summarized in Schemes 3.7 and 3.8. 

Wang et al. have discovered that ultrafme Ni powder in the presence of Cul, PPh3, and KOH promotes coupling of terminal alkynes with aryl and alkenyl iodides in high yields [65], Recent developments have shown, moreover, that the use of co-catalysts (Cu, Zn, Al, etc.) to facilitate the formation of the acetylides is not always required and that cross-coupling reactions of acetylenes and aryl halides can be performed successfully with Pd-based catalysts alone, even with difficult substrates [48, 66]... 

Terminal alkynes can be alkenylated by alkenyl triflates (bromides, iodides) in the presence of catalytic amounts of a palladium(O) complex (or a precursor thereof) and usually an additional substoichiometric amount of copper(I) iodide (Cul), and they can be arylated by aryl triflates (bromides, iodides). These reactions are called Cacchi coupling reactions if triflate reagents are employed, and Sonogashira-Hagihara coupling reactions if halides are used. 

Vinyliodonium ions, 35 and 36, are hypervalent iodine species in which one or two alkenyl ligands are bound to a positively charged iodine(III) atom. Although they are reactive with nucleophilic reagents, they are less labile than alkynyliodonium ions, and stable halide salts of vinyliodonium ions can be prepared. The first vinyliodonium compounds [i.e. (a, / -dichlorovinyl)iodonium salts] were synthesized by the treatment of silver acetylide-silver chloride complexes with (dichloroiodo)arenes or l-(dichloroiodo)-2-chloroethene in the presence of water (equation 152). The early work was summarized by Willgerodt in 1914115. This is, of course, a limited and rather impractical synthetic method, and some time elapsed before the chemistry of vinyliodonium salts was developed. Contemporary synthetic approaches to vinyliodonium compounds include the treatment of (1) vinylsilanes and vinylstannanes with 23-iodanes, (2) terminal alkynes with x3-iodanes, (3) alkynyliodonium salts with nucleophilic reagents and (4) alkynyliodonium salts with dienes. 

On the other hand, it is well known that stereodefined 1-alkyenyldialkylboranes are readily prepared by the monohydroboration of alkynes, i.e. dialkylboranes such as disiamylborane and catecholborane permit the monohydroboration of terminal alkynes, thus making readily available the corresponding (E)-l-alkenyldialkyl-boranes with high stereoselectivity, more than 99% (Eq. 97) . Highly pure (Z)-l-alkenyldialkylboranes (purity, more than 98%) are prepared without any difficulty via the monohydroboration of 1-halo-1-alkynes with disiamylborane or dicyclohexylborane, followed by treatment with t-butyllithium (Eq. 98) Consequently, if such 1-alkenyldialkylboranes react with 1-alkenyl halides or 1-alkynyl... 

The Pd-catalyzed cross-coupling of terminal alkynes with aryl and alkenyl halides in the presence of Cu(I) as co-catalyst to give arylalkynes and enynes is known as the Sonogashira coupling (first time reported by Kenkichi Sonogashira et ah). Triethylamine or diethylamine is used as a solvent. 

Several of the trialkylaluminum and alkylaluminum halides and hydrides mentioned above are commercially available. Alkynyl, alkenyl, cyclopentadienyl, and aryl derivatives are, in general, not commercially available and must be synthesized for laboratory use. Alkynyl derivatives can be prepared by salt metathesis, as in the reaction of Et2AlCl with NaC=CEt to give Et2AlC=CEt. The acidity of terminal alkynes is sufficient for preparation of alkynyl aluminum compounds by alkane or hydrogen elimination upon reaction with a trialkylaluminum or an aluminum hydride (equation 17), respectively. TriaUcynyl aluminum compounds are typically isolated as Lewis base adducts to stabilize them against otherwise facile polymerization. Alkenyl compounds of aluminnm have similarly been prepared. 

As described above (Section 5.2), the Stephens-Castro reaction of alkynylcopper with aryl and vinyl halides in boiling pyridine is a useful route to aryl and vinyl acetylenes. Direct cross-coupling of organic halides, such as sp halides, with terminal alkynes is a more convenient procedure. Such a reaction is not so easy, but it can be done using a Pd-complex catalyst [41]. Especially facile Pd-catalyzed cross-coupling of aryl and alkenyl halides with terminal alkynes proceeds smoothly under mild conditions in the presence of a cocatalyst of cuprous iodide in amine solvents [Eq. (28)] [42]. This methodology is now used widely for the constiuction of conjugated arylalkyne or enyne systems [43], as described below. It is attractive from a synthetic point of view because mild reaction conditions and simplicity of the procedure are associated with recent developments in modem acetylene chemistry [44]. 

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