Intramolecular Coupling of Diynes

Ruthenium-catalyzed reactions involving diynes generally lead to the intramolecular oxidative coupling of the two C=C bonds. Bicyclic compounds can be synthesized in the presence of another unsaturated molecule. 

The reaction of 1,6-heptadiynes with alkenes led to a [2+2+2] cyclotrimer-ization in the case of cyclic or linear alkenes possessing heteroatoms at the al-lylic position. Bicyclic cyclohexadienes were thus produced in good yields with RuCl(COD)C5Me5 [92,93] (Eq. 71). A ruthenacyclopentadiene is invoked as an intermediate in the mechanism. Insertion of the alkene becomes possible by a heteroatom-assisted reaction. 

With strained bicycloalkenes such as norbornene derivatives a ruthenium-catalyzed tandem cyclopropanation occurred together with common [2+2+2] cy-clotrimerization, showing a biscarbenoid hybride structure for the ruthenacyclopentadiene intermediate [92] (Eq. 72). 

Recently, a formal ruthenium-catalyzed [4+2+2] cycloaddition of 1,6-diynesto 1,3-dienes gave conjugated 1,3,5-cyclooctatrienes and vinylcyclohexadienes [94] (Eq. 73). Insertion of a double bond in the ruthenacyclopentadiene can lead to the formation of tetraenes or vinyltrienes which undergo a thermal elec-trocyclization. 

When the [2+2+2] cycloaddition of 1,6-diynes occurred in the presence of C=C bonds or C=N bonds, substituted benzenes or pyridines were obtained in good yields [95-98]. For example, anthraquinones were produced by reaction of l,2-bis(propiolyl)benzenes with a variety of monoalkynes [95] (Eq. 74). 

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In Section 9.2, intermolecular reactions of titanium—acetylene complexes with acetylenes, allenes, alkenes, and allylic compounds were discussed. This section describes the intramolecular coupling of bis-unsaturated compounds, including dienes, enynes, and diynes, as formulated in Eq. 9.49. As the titanium alkoxide is very inexpensive, the reactions in Eq. 9.49 represent one of the most economical methods for accomplishing the formation of metallacycles of this type [1,2]. Moreover, the titanium alkoxide based method enables several new synthetic transformations that are not viable by conventional metallocene-mediated methods. 

The catalytic intramolecular coupling of two C=C bonds at a ruthenium site leads to cyclization reactions. For example, although generally less reactive than a,co-diynes or enynes, 1,6-dienes react with [RuC12(COD)] in 2-propanol, leading to exo-methylenecyclopentanes in excellent yields [13] (Eq. 8). The mechanism suggests the formation of the ruthenacyclopentane(hydrido) intermediate 19. 

The reductive intramolecular coupling of a,a>-diynes is catalyzed by Pd(0) in the presence of P(o-tol)3, Et3SiH, and acetic acid. It is thought that a hydrido species, [Pd(H)(OAc)L2], initiates the reaction. The mechanistic scheme resembles that outlined in Scheme 19. The method is quite general and applicable to a wide range of substrates. ... 

Axially chiral biaryls are an important class of molecules for both biologically active compounds and chiral ligands (78-80). The most common approach to obtain biaryls is by aryl coupling followed by resolution of the racemic product to afford enantiopure biaryls. Even though enantioselective partial intramolecular cyclotrimerization of diyne with alkynes (81,82) or nitriles (83) were developed with various transitional metals, it was difficult to carry out complete intermolecular reaction. Using a cationic chiral rhodium complex as catalyst, a regioselective intermolecular cross-cyclotrimerization of alkynes 72 and 73 for... 

The intramolecular alkyne coupling of diyne 11.281 was used in a synthesis of bryostatin 11.283 to close the macrocycle 11.282 (Scheme 11.94). This reaction was followed by a gold(l)-catalysed 6-endo ring closure of 11.282 and some routine transformations to complete the synthesis. As so often in macrocyclizations, a low concentration (0.002 M) was found to be important. 

The Ti-promoted intramolecular alkyne-alkyne coupling of tethered diynes was extensively developed earlier with TiCp2 derivatives as reagents65 66 (Equation (1) of Scheme 22). Bicyclic titanacyclopentadienes fused to... 

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... 

Interestingly, seven-membered conjugated diyne complex 16 is produced by the acid-promoted Nicholas reaction of the dicobalt-coordinated bispropargylic complex (Equation (7)). The cyclization proceeds via an intramolecular coupling reaction between a propargyiic cation and an alkene produced after dehydration. The molecular structure of seven-membered diyne complex 16 is confirmed by X-ray analysis, although the decomplexation is not successfully carried out. 

Pd/tppts-catalysed intermolecular sp-sp couplings to afford diynes and sp2-sp coupling of 2-iodophenols or iodoanilines with alkynes followed by intramolecular cyclization to benzofurans and indoles, respectively, with moderate to good yields in H20/CH3CN solvent mixtures have also been described.517 8... 

A stereochemical study of the synthesis of unsaturated 1,4-aminoalcohols via the reaction of unsaturated 1,4-alkoxyalcohols with chorosulfonyl isocyanate revealed a competition between an retentive mechanism and an SnI racemization mechanism, with the latter having a greater proportion with systems where the carbocation intermediate is more stable.254 An interrupted Nazarov reaction was observed, in which a nonconjugated alkene held near the dienone nucleus undergoes intramolecular trapping of the Nazarov cyclopentenyl cation intermediate.255 Cholesterol couples to 6-chloropurine under the conditions of the Mitsunobu reaction the stereochemistry and structural diversity of the products indicate that a homoallylic carbocation derived from cholesterol is the key intermediate.256 l-Siloxy-l,5-diynes undergo a Brpnsted acid-promoted 5-endo-dig cyclization with a ketenium ion and a vinyl cation proposed as intermediates.257... 

An endo-exo intramolecular cyclization of a,P-diynylsulfides is brought about by iodonium salts and leads to fused 2H-1-benzothiopyrans (Scheme 118). The reaction is successful with 1,5-, 1,6-, and 1,7 diynes and a heteroatom can be accommodated in the alkyl chain. Furthermore, a substituent can be present at the other terminal site and the iodine which is perforce introduced into the fused alicyclic ring allows elaboration by Pd-catalyzed coupling with a variety of acetylenes <1998AGE3136>. 

Primary cations give both coupled and H-atom abstraction products. Secondary cations undergo coupling only, whereas tertiary cations with methyl substitutents show only H-atom abstraction and electrophilic coupling. The intramolecular variant of this reaction is particularly useful for the efficient synthesis of medium-sized 1,5-diynes and has been applied to the synthesis of hexacarbonyldicobalt-complexed 1,5-cycloctadiynes 31 and a cyclooct-5-ene-l,5-diyne derivative 32 (Scheme 14).121 The eight-membered rings... 

The method is limited because of the requirement for stoichiometric reagents, but impressive applications in the preparation of complex molecules have appeared. For example, a model system for ene-diyne antibiotics has been prepared by an intramolecular route (Scheme 19). Added versatility arises from the electophilic coupling of vinyl-propargyl complexes, such as in Friedel-Crafts acylation conditions. 

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