Enynes 1.4- , dimerization

Oligomerization of alkynes can lead to linear enyne dimers or afford cyclic oligomers. Dimerization of terminal acetylenes induced by Ru complexes yields stereoisomeric conjugated head-to-head enynes depending on the substituents 532... 

Lanthanide metallocene compounds are also active catalysts for the dimerization of terminal alkynes, giving predominantly the linear head-to-head enyne dimer with a double bond of E configuration [17]. In recent years, however, novel organo-lanthanide [13] and organoactinide [18, 19] systems have shown their ability to produce, with high selectivity, Z and geminal enyne products, respectively. 

Conjugate enynes dimerize to give aromatic products. 

Monomer 1 was prepared, with an overall yield of 71%, through a three step synthetic sequence, using known experiment procedures (18-20). Diyne dimer 2 was synthetized (94%) according to a mo fied Glaser oxidative catalytic coupling of 1 (27). Straus enyne dimer 2 (Z configuration) was obtained (83%),... 

The standard Sonogashira reaction conditions were not successful for the coupling reaction of 3-chloropyrazine 1-oxide (40) and 1-hexyne. In contrast, treatment of 40 and 1-hexyne with Pd(Ph3P)4 and KOAc produced 3-(l-hexynyl)pyrazine 1-oxide (41), together with the co-dimeric product, (E)-enyne 42 [34]. Presumably, the co-dimerization product 42 resulted from the cis addition of 1-hexyne to adduct 41. 

Enynes.1 Pd(OAc)2 when complexed with this phosphine (1 1) can effect coupling of two alkynes to provide dimeric 1,3-enynes. 

Several examples are known of the transition metal-catalyzed synthesis of 1,2,3-buta-trienes, which possess one more cumulated C=C double bond than allenes. Most of the reported examples of the butatriene synthesis involve dimerization of terminal alkynes and conjugated enynes are typical side products of the reactions. 

A variety of palladium-catalyzed dimerizations of conjugated enynes and their additions to diynes and triynes gave rise to styrene and phenylacetylene derivatives, respectively. Inter alia, 1,2,4-cyclohexatrienes have been invoked as intermediates in these reactions [134], 5,6-Diphenyl-l,2,4-cyclohexatriene has been proposed as an intermediate in the rearrangement of 4,4-diphenylcyclohexa-2,5-dienylidene to o-ter-phenyl and its possible existence was supported by quantum-chemical calculations [135],... 

Hashmi et al. investigated a number of different transition metals for their ability to catalyze reactions of terminal allenyl ketones of type 96. Whereas with Cu(I) [57, 58] the cycloisomerization known from Rh(I) and Ag(I) was observed (in fact the first observation that copper is also active for cycloisomerizations of allenes), with different sources of Pd(II) the dimer 97 was observed (Scheme 15.25). Under optimized conditions, 97 was the major product. Numerous substituents are tolerated, among them even groups that are known to react also in palladium-catalyzed reactions. Examples of these groups are aryl halides (including iodides ), terminal alkynes, 1,6-diynes, 1,6-enynes and other allenes such as allenylcarbinols. This che-moselectivity might be explained by the mild reaction conditions. 

The dimerization of alkynes is a useful method for forming compounds such as enynes from simple alkynes [13]. The iridium-catalyzed dimerizahon of 1-alkyries was first reported by Crabtree, and afforded (Zj-head-to-head enynes using [Ir(biph)(PMe3)Cl] (biph = biphenyl-2,2 -diyl) as a catalyst [14]. Thereafter, an iridium complex generated in situ from [Ir(cod)Cl]2 and a phosphine ligand catalyzed the dimerizahon of 1-alkynes 1 to give (Tj-head-to-head enyne 2, fZj-head-to-head enyne 3, or 1,2,3-butatriene derivatives 4 in the presence of hiethylamine... 

The regio- and stereoselective dimerization of terminal alkynes into disubstituted enynes is efficiently catalyzed by rare-earth metal alkyl and hydride complexes, as reported independently by Bercaw et al. and Teuben et al. in 1987 [211,212]. Takaki and coworkers have shown that complexes Ln[N(SiMe3)2]3 when combined with an amine additive (typically, ArNH2 compounds) afford an active species for the... 

When desired vinylidene-mediated pathways are not sufficiently favorable. Group 9 metal catalysts can access a set of typical side-reaction pathways. Alkyne dimerization to give conjugated enynes or higher oligomers is often observed. Polysubstituted benzenes resulting from [2 + 2 + 2] alkyne cyclotrimerization are also common coproducts. Fortunately, the selectivity of rhodium and iridium catalysts can often be modulated by the variation of spectator ligands. 

Under optimized conditions, cycloisomerizations of a number of functionalized hept-l-en-6-ynes took place in good-to-excellent yields (Table 9.3). Heteroatom substitution was tolerated both within the tether and on its periphery. Alkynyl silanes and selenides underwent rearrangement to provide cyclized products in moderate yield (entries 6 and 7). One example of seven-membered ring formation was reported (entry 5). Surprisingly, though, substitution was not tolerated on the alkene moiety of the reacting enyne. The authors surmize that steric congestion retards the desired [2 + 2]-cycloaddition reaction to the point that side reactions, such as alkyne dimerization, become dominant. 

The catalyst prepared from PPh3 and a simple Ir(I) salt, [IrCl(cod)]2, promotes ( )-selective head-to-head dimerization in good yield, while the combination of [IrCl (cod)]2 with an electron-rich phosphine (PPrj) affords (Z)-enynes with reduced efficiency, but comparable selectivity. The results of [rrCl(cod)]2/PPr3-catalyzed dimerization reactions carried out according to Scheme 9.10 are summarized in Table 9.10. 

Most of these catalytic systems are able to dimerize either aromatic alkynes, such as phenylacetylene derivatives, or aliphatic alkynes, such as trimethylsilylacetylene, tert-butylacetylene and benzylacetylene. The stereochemistry of the resulting enynes depends strongly on both the alkyne and the catalyst precursor. It is noteworthy that the vinylidene ruthenium complex RuCl(Cp )(PPh3)(=C=CHPh) catalyzes the dimerization of phenylacetylene and methylpropiolate with high stereoselectivity towards the ( )-enyne [65, 66], and that head-to-tail dimerization is scarcely favored with this catalyst. It was also shovm that the metathesis catalyst RuCl2(P-Cy3)2(=CHPh) reacted in refiuxing toluene with phenylacetylene to produce a... 

The metallation of 3,1-enynes and 1,3-diynes with butyllithium requires careful experimentation, because dilithiation (and in the case of the enynes subsequent dimerization) occurs when the base is present in excess [2,41] ... 

Differolide is synthesized by dimerization of the enyne metathesis product of allyl propiolate (Equation (18)). ... 

Scheme 1. Linear and branched enyne isomers from dimerization of alkynes.

Palladium catalysts enable the dimerization of functional alkynes with selective head-to-tail coupling in the presence of bulky phosphine ligands, for both homocoupling of terminal alkynes or cross-coupling of mono and disubstituted alkynes [4, 6]. On the other hand, a palladium/imidazolium system gives linear (E)-enynes as the predominant products [7]. 

Mononuclear ruthenium complexes have become useful catalysts, not only because they can have high regio- and stereoselectivity but also because their catalyzed reactions rely on an elucidated mechanism. This true for the cis-dihydride (PP3)RuH2 complex, a catalyst precursor for the selective head-to-head dimerization of phenylacetylene to the corresponding (Z)-enyne, via bis(alkynyl) active spe-... 

The rhodium-trimethylphosphine system is remarkable because it catalyzes the dimerization of aryl substituted acetylenes, yielding the scarce branched head-to-tail coupling product [12], The iridium species generated from [Ir(COD)Cl]2 and phosphine selectively yields linear ( ) or (Z) enynes from silylalkynes, depending on whether triaryl or tripropylphosphines, respectively, are used [16]. 

The dimerization of 1 -alkynes to enynes by transition metal catalysts occurs either via alkynyl-vinylidene M(C=CR)(=C=CHR) or alkynyl-alkyne M(C=CR)(if-HC=CR) coupling, by insertion into the a Ru-C bond. Selectivity control depends on the previous orientation of the alkyne/vinylidene moiety. 

Palladium catalysts have high tolerance for several functional groups irrespective of their gem- or fc -sclcctivity [4, 6, 7]. Aldehydes, alcohols, saturated or conjugated ketones, esters, sulfones, malonates and silyl ethers have proved to be compatible. The presence of an additional double bond does not modify the coupling, enabling self-dimerization of non-conjugated enynes as depicted in Scheme 8. 

Scheme 8. Catalytic dimerization of non-conjugated enynes with the Pd(OAc)2/TDMPP system.

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