Alkynes intermolecular coupling

The benzene derivative 409 is synthesized by the Pd-catalyzed reaction of the haloenyne 407 with alkynes. The intramolecular insertion of the internal alkyne, followed by the intermolecular coupling of the terminal alkyne using Pd(OAc)2, Ph3P, and Cul, affords the dienyne system 408, which cyclizes to the aromatic ring 409[281]. A similar cyclization of 410 with the terminal alkyne 411 to form benzene derivatives 412 and 413 without using Cul is explained by the successive intermolecular and intramolecuar insertions of the two triple bonds and the double bond[282]. The angularly bisannulated benzene derivative 415 is formed in one step by a totally intramolecular version of polycycli-zation of bromoenediyne 414[283,284],... 

The 121/Cl3SiH combination selectively cross-couples alkenes with alkynes intermolecularly to give acyclic homoallylic silanes 127 and 128 (Eq. 22) [73]. 

The moderate level of regioselectivity seen in the alkyne insertion is dependent on added PPI13, but the alkene insertion occurs with excellent regioselectively. This is the only catalytic, late transition metal system shown to intermolecularly couple alkenes with alkynes. 

Although a fair number of examples of the Ti-promoted intermolecular alkyne-alkene coupling reactions are known, those that display high pair selectivity and regioselectivity are still relatively limited. Some representative examples are shown in Scheme 18 51 53>53a... 

Scheme 18 Ti-promoted intermolecular 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). 

The Pd-catalyzed electro-cleavage of the C—O bond of allyl aryl ether proceeds smoothly in a DMF-Bu4NBp4-(Mg)-(Stainless Steel) system, giving depro-tected products in 73 99% yield [437]. The sp-sp intermolecular coupling reaction with the Pd water-soluble catalyst prepared in situ from Pd(II) acetate and sul-fonated triphenylphosphine in an MeCN-H2O system yields diynes in 45 65% yields [438]. Similarly, the sp -sp coupling of 2-iodophenols or 2-iodoanilines and terminal alkynes followed by intramolecular cyclization gives indol and furan... 

In a similar way, a novel route for synthesis of cr,/ -unsaturated amide 242 is explored via intermolecular coupling of four components, that is, alkyne, hydrosilane, amine, and GO (Equation (41)). All of these components are assembled in the ordered manner with the assistance of an Rh complex. Pyrrolidine as a nucleophile gives the best results. None of the alcohols can participate in a similar transformation. 

Intermolecular coupling of ketyls with alkynes has proven successful in some instances [63]. Using this protocol, allylic alcohols are typically generated in good yields, but often as a mixture of E/Z isomers (Eq. 54). Additionally, some type of activation of the triple bond is necessary. In particular alkynyloxiranes have proven to be very useful substrates for the generation of to 2,3-pentadiene-l,5-diols (Eq. 55)... 

As was the case for the intermolecular coupling reactions, activated alkenes and alkynes constitute one important class of acceptors for the ketyl radical anions. Notably, even highly strained four-membered rings can be accessed via a 4-exo cyclization process (Eq. 56) [65]. 

The use of enals in nickel-promoted intermolecular couplings was initially limited to stoichiometric [3 -1- 2]/[2 + 1] cycloadditions [26], This limitation was overcome with the development of a Ni(COD)2/PCy3/R3SiH/THF reaction system, whereby the reductive coupling of alkynes and enals was achieved to afford a highly chemo- and stereo-selective synthesis of Z-enol silanes (Scheme 8.6) [27]. 

Intermolecular couplings involving aldehydes, terminal alkynes, and organoz-incs also proceeded with high levels of chemo- and regioselectivity (Scheme 8.15). However, unlike intramolecular couplings, direct addition of more reactive... 

Intermolecular aldehyde/alkyne reductive couplings involving PBua and EtaB have been explored on a variety of systems ranging from simple to quite complex [22]. Aromatic alkynes are generally the best substrates, whereas more substrate generahty is observed on the aldehyde component (Scheme 7). In the course of examining asymmetric couplings (see Sect. 2.2.4), a variety of different monodentate phosphines were examined [23]. 

The combination of Ni(COD)2/NHC complexes with EtsSiH as the reducing agent has also proved to be effective in intermolecular couplings of aldehydes and alkynes (Scheme 9) [21]. A broad range of substrates underwent couplings, including aromatic, non-aromatic, and terminal alkynes as well as branched, unbranched, and aromatic aldehydes. The regioselectivity with... 

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