Intramolecular Alkene-Alkyne Coupling

The tethering of the alkene and alkyne expands the scope of alkene partners to include more hindered disubstituted alkenes and especially trisubstituted alkenes. Equations 1.47 and 1.48 show two differently arranged trisubstituted alkene partners as well as being able to form five- and six-membered rings [45, 46]. 

In previous work using Pd catalysts, cycloisomerizations involving substrates bearing siloxy groups at the allylic position generated 1,3-dienes preferentially (Equation 1.49, path a), in contrast to their normal behavior [47]. In the Ru-catalyzed version, the normal 1,4-diene is obtained (Equation 1.49, path b), which generates a very useful enol silyl ether with excellent chemo-, regio-, and diastereoselectivity [48]. 

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On the other hand, unsaturated aldehydes and ketones were obtained using allylic alcohols as alkene components [68]. Similarly, allyl f-butyldimethylsilyl ether and N-allylamides gave silyl enol ethers [69] and enamides [70], respectively. The ruthenium-catalyzed alkene-alkyne coupling was successfully combined with the palladium-catalyzed intramolecular asymmetric allylic alkylation [71] to provide a novel one-pot heterocyclization method [72]. 

Scheme 10.66 Regioselective intramolecular carbotitanation of alkenes leading to the products of intermolecular alkene-alkyne coupling [52].

As noted in the introduction, in contrast to attack by nucleophiles, attack of electrophiles on saturated alkene-, polyene- or polyenyl-metal complexes creates special problems in that normally unstable 16-electron, unsaturated species are formed. To be isolated, these species must be stabilized by intramolecular coordination or via intermolecular addition of a ligand. Nevertheless, as illustrated in this chapter, reactions of significant synthetic utility can be developed with attention to these points. It is likely that this area will see considerable development in the future. In addition to refinement of electrophilic reactions of metal-diene complexes, synthetic applications may evolve from the coupling of carbon electrophiles with electron-rich transition metal complexes of alkenes, alkynes and polyenes, as well as allyl- and dienyl-metal complexes. Sequential addition of electrophiles followed by nucleophiles is also viable to rapidly assemble complex structures. 

However, the greatest amount of work in the area of intramolecular cation-radical coupling reactions involves annulation of less ionizable alkenes (or alkynes) with enol ethers or vinyl sulfides. Typically, these reactions are used to form six-159,163 or five-membered165 rings, usually stereospecifically (Schemes 67 and 68, respectively). As seen... 

Intramolecular geometries, database studies, 1, 597 Intramolecular hydroalkoxylation, and etherification, 10, 672 Intramolecular pinacol coupling to cyclic 1,2-diols, 11, 51 with samarium reagents, 11, 60 Intramolecular silylformylation, alkynes and alkenes, 11, 489 Intramolecular solvomercuration alkenes, 2, 436 alkynes, 2, 439... 

Alkyne-alkene carbonylative coupling. Intramolecular carbonylative coupling of dialkynes catalyzed by Fe(CO)3 provides a route to cyclopentadienones (equation I). The more difficult carbonylative alkyne-alkene coupling to provide cyclopen-tenones (Pauson-Khand reaction) can also be effected with Fe(CO)s, but in modest yield. In an improved coupling, acetone is treated with Fe2(CO)9 to form Fe-... 

Dimethylbutadiene)HfCp (Cl)] (74c) reacts with one molar equivalent of acetylene to yield the unusual product 87. This is probably formed by a conventional butadiene/alkyne coupling at the Group 4 metal center, followed by an intramolecular alkene insertion into the adjacent hafnium to carbon cr-bond. The resulting alkylidene complex (86) then rapidly dimerizes to yield the observed final product (see Scheme 28), that was characterized by X-ray diffraction.96... 

From a synthetic point of view, bond forming steps are the most important reactions of radical ions [202]. Several principle possibilities have been described in Section 8.1 and are summarized in Scheme 52. Many carbo- and heterocyclic ring systems can be constructed by (inter- and intramolecular) radical addition to alkenes, alkynes, or arenes. Coupling of carbonyl radical anions leads to pinacols either intra-or inter-molecular which can be further modified to give 1,2-diols, acyloins or alkenes. Radical combination reactions with alkyl radicals afford the opportunity to synthesize macrocyclic rings. These radical ion-radical pairs can be generated most efficiently by inter- or intramolecular photoinduced electron transfer. 

Coupling of alkenes/alkynes. CpzZrBua is most often employed to couple unsaturated compounds to provide alkenes and dienes. An intramolecular version is useful for a stereoselective synthesis of c -l,2-dimethyl cyclic systems. ... 

Scheme 3.10 Tandem alkene-alkyne cross-coupling reaction-intramolecular het-erocyclisation reaction catalysed hy a combination of ruthenium catalysis and chiral palladium catalysis.

Scheme 19 Ti-promoted intramolecular alkyne-alkene coupling.

Trost and others have extensively studied the ruthenium-catalyzed intermolecular Alder-ene reaction (see Section 10.12.3) however, conditions developed for the intermolecular coupling of alkenes and alkynes failed to lead to intramolecular cycloisomerization due the sensitivity of the [CpRu(cod)Cl] catalyst system to substitution patterns on the alkene.51 Trost and Toste instead found success using cationic [CpRu(MeCN)3]PF6 41. In contrast to the analogous palladium conditions, this catalyst gives exclusively 1,4-diene cycloisomerization products. The absence of 1,3-dienes supports the suggestion that the ruthenium-catalyzed cycloisomerization of enynes proceeds through a ruthenacycle intermediate (Scheme 11). 

Esteruelas and coworkers reported the stoichiometric Diels-Alder type addition of dienes to the Cp-Cy double bond of allenylidene complexes to give the corresponding substituted vinylidene complexes (Equation 7.7) [33]. The results of this stoichiometric reaction prompted us to investigate the diruthenium complex-catalyzed allenylidene-ene reaction between alkenes and the Cp-Cy double bond of an allenylidene moiety. Results of inter- and intramolecular allenylidene-ene reactions providing novel coupling products between alkynes and alkenes are described in this section [34]. 

Macrolactone synthesis 6,51, 71, 72, 94, 124,131,163,187,195 McMurry coupling 43 Medium ring synthesis 43,45,75, 77 Metathesis, Alkene (see Grubbs) Metathesis, Alkyne (see alkyne metathesis) Michael addition Intramolecular 166,166, 167,201 Intermolecular 57,84, 153, 166,204... 

In our attempt to extend the coupling reaction of arenes with alkenes to the coupling with alkynes, as shown in Scheme 4, it was found that the reaction of arenes with ethyl propiolate in TFA (trifluoroacetic acid) gave addition products instead of a coupling product [3]. This addition reaction has been extended to various alkynes and various arenes and also to intramolecular reactions for synthesis of heterocycles such as coumarins, quinolines, and thiocoumarins. 

Cyanosilylation of alkynes with Me3SiCN is effectively catalyzed by a PdCl2 complex.263 Its intramolecular version is valuable for the stereo-defined synthesis of tri- and tetrasubstituted alkenes.264 A Pd-catalyzed system effects an efficient three-component coupling of Me3SiCN, highly electron-deficient alkenes, and allyl chlorides (Equation (69))/ 3 The... 

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