Diynes applications

The total synthesis of ( )-estrone [( )-1 ] by Vollhardt et al. is a novel extension of transition metal mediated alkyne cyclotrimeriza-tion technology. This remarkable total synthesis is achieved in only five steps from 2-methylcyclopentenone (19) in an overall yield of 22%. The most striking maneuver in this synthesis is, of course, the construction of tetracycle 13 from the comparatively simple diyne 16 by combining cobalt-mediated and ort/io-quinodimethane cycloaddition reactions. This achievement bodes well for future applications of this chemistry to the total synthesis of other natural products. 

The preparation of condensed rhodacyclopentadienes via the diyne reaction, and examples of their use in heterocyclic synthesis have been described earlier (see Schemes 79 and 86 in Sections IV,B,5 and IV,C,2). An example showing the application of this approach to the synthesis of a condensed triazole is shown in Scheme 127.192... 

A variety of heterocyclic compounds has been synthesized via condensed rhodacyclopentadienes (the diyne reaction ) (see for example Scheme 86 in Section IV,C,2). An example of the application of this type of process leading to the formation of a tribenzothiepin in outlined in Scheme 176.245 The bisacetylene derivative 149 can also be converted into a dibenzo[h,/] azuleno[l,2-d]thiepin derivative by means of (PhCN)2PdCI2 (cf. Scheme 172 in Section VI,A). 

Recently (82), pure 3,5-dimethylcyclohexenone epoxide was obtained by Toda using a complexation method with optically active 1,6-di(o-chlorophenyl)-l,6-diphenylhexa-2,4-diyne-l,6-diol. The method was not applicable to unsubstituted 2,3-epoxycyclohexanone (82). 

Alkynes react with haloethenes [38] to yield but-l-en-3-ynes (55-80%), when the reaction is catalysed by Cu(I) and Pd(0) in the presence of a quaternary ammonium salt. The formation of pent-l-en-4-ynes, obtained from the Cu(I)-catalysed reaction of equimolar amounts of alk-l-ynes and allyl halides, has greater applicability and versatility when conducted in the presence of a phase-transfer catalyst [39, 40] although, under strongly basic conditions, 5-arylpent-l-en-4-ynes isomerize. Symmetrical 1,3-diynes are produced by the catalysed dimerization of terminal alkynes in the presence of Pd(0) and a catalytic amount of allyl bromide [41]. No reaction occurs in the absence of the allyl bromide, and an increased amount of the bromide also significantly reduces the yield of the diyne with concomitant formation of an endiyene. The reaction probably involves the initial allylation of the ethnyl carbanion and subsequent displacement of the allyl group by a second ethynyl carbanion on the Pd(0) complex. 

In addition to their role as a source of lithiated diynes or terminal diynes silyl-protected diynes have found direct application in the preparation of Group 8 diynyl complexes. Reactions of Me3SiC=CC=CR (R = Ph, C=CPh, C=CC=CPh) with RuCl(PPh3)2Cp in the presence of KF afford the corresponding poly-ynyl complexes Ru(C=CC=CR)(PPh3)2Cp." ... 

The first tt complexes of 1,3-diynes were reported by Greenfield. Shortly thereafter, Tilney-Bassett described the first heterometallic derivatives. This area has grown steadily since these initial reports and many complexes of this type are now known. Diyne complexes are often simply alkyne-substituted analogues of conventional jr-alkyne complexes. Indeed, transition metal compounds that form -complexes with mono-alkynes can be expected to form complexes with diynes. However, the thermal sensitivity of terminal diynes, especially 1,3-butadiyne, may limit the application of routine reaction conditions in some cases. Further coordination of the ynyl ligand by additional metal fragments is usually determined by the reagent stoichiometry and by steric effects. 

Application of the coupling reactions described in the previous section has given many organometallic complexes of ligands containing diyne fragments, which may not be directly coordinated to a metal center. The following surveys this area briefly and describes some recent applications of these systems in the construction of novel molecular architectures. 

Rhodium-catalyzed alkyne cyclotrimerization is also applicable to the synthesis of a polyalkyne substrate bearing ether-linked 1,6-diyne moieties 59, which is easily prepared by Pd-Cu-catalyzed Sonogashira couphng reactions. These reactions provide a novel and efficient synthetic route to oligophenylene 60, which bears benzodihydrofur-an moieties (Scheme 7.17) [40]. 

The cascade silylcarbocyclization is applicable to diynals. For example, the reaction of undec-l,6-diyn-ll-al 72 with PhMe2SiH, catalyzed by Rh(acac)(CO)2 affords the corresponding silylated exo-silylmefhylene(hydroxy)bis(cyclopentylidene) 73 (Eq. 20) [48]. 

Cook and co-workers took advantage of the molybdenum-based methodology and reported one of the most graceful applications of the allenic PKR. They intended to use PKR to synthesize a theoretically interesting tetracyclic compound 55, which has 14 vr-electrons and is supposed to be aromatic in principle. To this end, they have applied PKR to various alkynyl allenes, and finally employed a diyne-diallene substrate 54 successfully (Equation (27)). Double PKR by employing molybdenum hexacarbonyl in excess and DMSO afforded the requisite intermediate in a high yield. 

This type of intramolecular silylformylation is applicable to 4-silyloxy-l,6-diyne 176 which gives 177 in good yields (Equation (31)). The remaining alkynyl moiety in 177 can further undergo intermolecular silylformylation. " ... 

The use of a zirconium complex (dibutylzirconocene, — 78 °C to rt, 2 h) to induce intramolecular co-cyclization of A-methyl-5-azanona-l,8-diene to an intermediate zirconacycle was a key step in a new azepane synthetic route hydrolysis (MeOH, aq. NaHC03) of this intermediate then realized the trans- 1,4,5-trimethylazepane in 75% yield the active reagent for the initial cyclization was zirconocene (1-butene). The overall transformation represents a type d ring construction process <2006SL3439>. This synthetically versatile process is also applicable to aza eneyne and aza diyne precursors as well as benz-fused analogues. 

Various metal acetylides are used for smooth coupling with propargylic halides and acetates. 2,3-Alkadien-5-yn-l -ols are obtained by the reaction of 2-(l -alkynyl)oxiranes [28,29], As a synthetic application, the unstable 2,3-octadiene-5,7-diyn-l-ol (136), a fungus metabolite, has been synthesized by the coupling of 4-trimethylsilylbutadiy-nylzinc chloride (134) with 2-ethynyloxirane (135) followed by desilylation [31]. 

Lei, A. Srivastava, M. Zhang, X. Transmetala-tion of Pd enolates and its application in the Pd-catalyzed homocoupling of alkynes a room-temperature, highly efficient route to diynes./. Org. Chem. 2002, 67,1969-1971. 

Oxidative coupling of phenylethynesis another Cu-catalyzed reaction that involves one-electron redox steps. Substituted, conjugated alkynes are valuable components for liquid crystal applications. Auer et al. (181) used a calcined CuMgAl-LDH-C03 to catalyze the air oxidation of phenylethyne to give l,4-diphenylbuta-l,3-diyne ... 

In the polycoupling reactions, the formation of the diyne units proceeded via a Glaser-Hay oxidative coupling route [35-38]. Despite its wide applications in the preparation of small molecules and linear polymers containing diyne moieties, its mechanism remains unclear [38-40]. It has been proposed that a dimeric copper acetylide complex is involved, whose collapse leads to the formation of the diyne product (Scheme 9). 

Oraganosilicon compounds react with a wide variety of organic electrophiles in the presence of a palladium catalyst and a Lewis base activator such as a fluoride or hydroxy ion to give the corresponding coupled products. The reaction is applicable to synthesis of diynes, enynes, arylacetylenes, alkenylarenes, biaryls, allylarenes and alkylarenes in addition to 1,3-, 1,4- and 1,5-dienes with tolerance for various functional groups. 

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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