1-Alkynes reaction with alkenyl halides

This reaction is useful in conjunction with E2 elimination to prepare alkenyl halides, allenes, and alkynes. Cycloalkenyl halides are easily prepared, but because of angle strain the cycloalkynes and cycloallenes with fewer than eight atoms in the ring cannot be isolated (see Section 12-7) ... 

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]. 

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

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 intramolecular insertion of an internal alkyne into an aryl or alkenyl halide 727 generates aryl- or alkenylpalladium as an intermediate, which is trapped with an organozinc or organostannane to give 728. Overall cis addition to the alkyne takes place[595,596]. The reaction of the alkenylstannane 730 with the 2-bromomethylfuran 729 is used for the introduction of a prenyl group[597]. 

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. 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

Use of alkenyl halides in this reaction has proven to be an effective method for the synthesis of enynes.116 117 The reaction can be carried out directly with the alkyne, using amines for deprotonation. 

Radical carbonylation reaction serves as a powerful tool for the synthesis of a range of carbonyl compounds. Radical carbonylation has been successfully applied to the synthesis of functionalized ketones from alkyl, aryl, and alkenyl halides.The radical aminocarbonylation reaction of alkynes and azaenynes provided efficient routes to 2-substituted acrylamides, lactams, and pyrrolidinones. For example, the aminocarbonylation of 4-pentyn-l-yl acetate 318 initiated by tributyltin hydride (Bu"3SnH) (30mol%) with AIBN (20mol%) gave acrylamide 325 in 92% yield (Scheme 43).A proposed mechanism starts from the addition of tributyltin radical 319 to alkyne... 

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. 

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. 

In the absence of a catalyst, alkynes react very slowly with bromine. Scheme 3.28 particularly when compared to alkenes. When a choice exists, bromine reacts preferentially with an alkene rather than an alkyne. It is possible that radical reactions play a more important role in the addition to alkynes. When the reaction of acetylene with chlorine is catalysed by iron(lll) chloride, the reaction is fast and 1,1,2,2-tetrachloroethane is formed. The uncatalysed addition of a hydrogen halide gives a tram alkenyl halide. Further addition is restricted but can give rise to dihalides. 

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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