1.4- Diyn-3-ones

Bromo-15-docosene-1,3-diyn-5-ol, B-00012 16-Bromo-15-docosene-1,3-diyn-5-one, B-00013... 

In principle the number of triple-bond stretching vibrations for a conjugated polyyne is expected to be the same as the number of triple bonds ". For symmetrical diynes, one mode should be i.r.-active and one Raman-active for symmetrical triynes, one should be i.r.-active and two Raman-active, etc. Because of the low force constant of the single bonds which separate the acetylene units compared to that of a triple bond, the splittings are small, and only with some of the lower polyynes is the anticipated number of absorption bands observed (see Table 7). The intensity of the C C bands in the i.r. increases with the number of triple bonds, and with Ph(C=C)6Ph, for example, it is the strongest band in the spectrum . 

In order to prepare nonsymmetrical diynes, one can use the Cadiot-Chodkiewicz reaction. It involves a haloalkyne such as a iodoalkyne or a bromoalkyne. Combined with the Glaser dimerization, this reaction provides a powerful entry to oligoyne bridging ligands and has been used extensively by Gladysz (see Figure 10) [34]. 

Probably the synthetically most useful versions of cyclotrimerization have been developed in the /ntromolecular sense through the pioneering work of Vollhardt. Since this topic has been thoroughly reviewed (95], we point out here only that the most powerful cyclocouplings have been two-component (e.g., diyne + mono-yne) or single component (e.g., ene-diyne) ones. The former strategy is elegantly illustrated in the CpCo(CO)2-catalyzed synthesis of estrone (61) depicted in Scheme 4-29 [105]. 

N. Sakai, N. Uchida, T. Konakahara, Synlett 2008, 1515-1519. Facile and selective synthesis of propargylic amines and 1,6-diynes one-pot three-component coupling reactions of alkynylsilanes, aldehydes and amines by a cooperative catalytic system comprised of CuCl and Cu(OTf)j. 

Reactions of Intermediate 3-2 with the Second and Third Molecules of Nitrile Formation of 5-Azaindoles from One Si-Tethered Diyne, One 1-BuCN, and Two Identical or Different Organonitriles... 

Formation of 5-Azaindoles 3-18 (Type III) from One Si-tethered Diyne, One t-BuCN, and Two Identical Oi nonitriles. A Typical Procedure for the Preparation of 4-tert-Butyl-2,6-dicyclohexyl-3,7-diphenyl-lff-pyrrolo[3 -c] pyridine(3-18a) To a toluene (10 ml) solution of CP2Z1CI2 (1.05 mmol, 307 mg) at —78 °C (dry ice/acetone) in a 20-ml Schlenk tube was added dropwise n-BuLi (2.1 mmol, 1.6 M, 1.32 ml) with a syringe. After the addition was complete, the reaction mixture was stirred at -78 °C for 1 h. Then, 1 mmol of bis(phenylethynyl) dimethylsilane was added, and the reaction mixture was warmed up to 50 °C and stirred at this temperature for 1 h. After trimethylacetonitrile (2.0 mmol, 166 mg. 

According to Shostakovskii and Bogdanova (71 Mil), the role of eatalyst is the formation of a nonpolar 7r-eomplex one of whose triple bonds has a uniform eleetron density distribution on both earbon atoms, thereby faeilitating the interaetion between the nueleophilie nitrogen atom and the fourth earbon atom in the eonjugated diyne system. 

Compounds with more than one triple bond are called diyne.s, triynes, and so forth compounds containing both double and triple bonds are called enynes (not ynenes). Numbering of an enyne chain starts from the end nearer the first multiple bond, whether double or triple. When there is a choice in numbering, double bonds receive lower numbers than triple bonds. For example ... 

While diene metathesis or diyne metathesis are driven by the loss of a (volatile) alkene or alkyne by-product, enyne metathesis (Fig. 2) cannot benefit from this contributing feature to the AS term of the reaction, since the event is entirely atom economic. Instead, the reaction is driven by the formation of conjugated dienes, which ensures that once these dienes have been formed, the process is no longer a reversible one. Enyne metathesis can also be considered as an alkylidene migration reaction, because the alkylidene unit migrates from the alkene part to one of the alkyne carbons. The mechanism of enyne metathesis is not well described, as two possible complexation sites (alkene or alkyne) exist for the ruthenium carbene, leading to different reaction pathways, and the situation is further complicated when the reaction is conducted under an atmosphere of ethylene. Despite its enormous potential to form mul-... 

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

When chromium atoms were cocondensed at 77 K with 1,7-cyclodeca-diyne (38), complexation was not observed however, an organic trimer of the starting material was formed. Standard, organic characterization-techniques showed that this trimer is the one depicted, rather... 

In this method, one alkyne is treated with Schwartz s reagent (see 15-17) to produce a vinylic zirconium intermediate. Addition of MeLi or MeMgBr, followed by the second alkyne, gives another intermediate, which, when treated with aqueous acid, gives the diene in moderate-to-good yields. The stereoisomer shown is the one formed in usually close to 100% purity. If the second intermediate is treated with I2 instead of aqueous acid, the 1,4-diiodo-1,3-diene is obtained instead, in comparable yield and isomeric purity. This reaction can also be done intramolecularly Diynes 56 can be cyclized to ( , E) exocychc dienes 57 by treatment with a zirconium complex. 

The hybrid cyclic pentayne 181 underwent Diels-Alder reaction with the electron-deficient diene tetrachlorothiophene 1,1-dioxide 192, but only at one of the two triple bonds of the 1,3-diyne moiety. This was followed by loss of SO2 to give the tetrachlorobenzannelated cyclotetradecenetetrayne 193 (Scheme 37) [18]. 

A plausible mechanism for the [2+2+2] cycloaddition reactions between diynes and heterocumnlenes (or nitriles) is shown in Scheme 5.16. Initially [2+2] oxidative addition of one alkyne and the heterocnmnlene (or nitrile) forms the five-mem-bered intermediate 54 compound 55 is formed after the insertion of the second alkyne and finally the seven-membered compound 55 undergoes reductive elimination to afford the prodnct 56 and regenerate the Ni(0) catalyst. 

Terminal diynes could not be cleanly monoliydrozirconated it was necessary to protect one of the two acetylenic forms with EtMgBr/TMSCl to get single addition [85]. 

The THF adduct 70 (mp 147 °C) and pyridine adduct 71 (mp 178°C) of bis-l-boraadamantane with one CH2 bridge were synthesized by hydroboration-cyclization of the bis-bicycle 72, available from hepta-l,6-diyne (Scheme 28) . 

The cobalt-catalyzed cooligomerization of diynes with nitriles allows a simple one-step synthesis222 of condensed pyridine derivatives including difficultly accessible 5,6,7,8-tetrahydroisoquinolines223 The synthesis is a versatile one in that pyridines condensed with five- and seven-membered carbocyclic rings can also be achieved in moderate yield in similar fashion. Additional attractive features of this simple synthesis are the formation of condensed isoquinolines by the use of functionalized nitriles and the pronounced regioselectivity observed when dissymmetrical diacetylenes are employed (Scheme 148).222... 

Beyond palladium, it has recently been shown that isoelectronic metal complexes based on nickel and platinum are active catalysts for diyne reductive cyclization. While the stoichiometric reaction of nickel(O) complexes with non-conjugated diynes represents a robust area of research,8 only one example of nickel-catalyzed diyne reductive cyclization, which involves the hydrosilylative cyclization of 1,7-diynes to afford 1,2-dialkylidenecyclohexanes appears in the literature.7 The reductive cyclization of unsubstituted 1,7-diyne 53a illustrates the ability of this catalyst system to deliver cyclic Z-vinylsilanes in good yield with excellent control of alkene geometry. Cationic platinum catalysts, generated in situ from (phen)Pt(Me)2 and B(C6F5)3, are also excellent catalysts for highly Z-selective reductive cyclization of 1,6-diynes, as demonstrated by the cyclization of 1,6-diyne 54a.72 The related platinum bis(imine) complex [PhN=C(Me)C(Me)N=Ph]2Pt(Me)2 also catalyzes diyne hydrosilylation-cyclization (Scheme 35).72a... 

In the case of unsymmetrical alkynes, the carboxylation yielded a mixture of regioisomers. But the reaction in the carbon atom having an alkyl substituent in the alkyne unit seemed to be more preferred than the one with an aryl substituent (Scheme 24).30 The carboxylation of conjugated diynes by Ni/PTMDA under electrolytic conditions took place predominantly at an internal carbon atom of the diyne unit to give 74 as a major product (Scheme 25)38 When Ni(cod)2/DBU was used as a catalyst, however, the carboxylation occurred exclusively at the terminal carbon (Scheme 26).31... 

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. 

Molecular scaffoldings with tetraethynylethenes (TEEs, 3,4-diethynylhex-3-ene-l,5-diynes) and trans-1,2-diethynylethenes [DEEs, (E)-hex-3-en-l,5-diynes] are at a particularly advanced stage.114,37 38 441 A collection of dose to one hundred partially protected and functionalized derivatives have been prepared in the meantime, providing starting materials for the perethynylated dehydroannulenes and expanded radialenes shown in Figure 6.136 441 TEEs and DEEs, as well as dimeric derivatives substituted at the terminal alkynes with donor (D, p-(dimethyl-... 

---