Diynes monoalkynes

The Ir-catalyzed [2+2+2] cycloaddihon of diynes and monoalkyne advocates a new synthehc approach to silafluorenes [13]. The Ir-PPh3-complex-catalyzed reac-hon of benzene and silicon-tethered 1,6-diynes with disubstituted alkynes gave tetra-subshtuted silafluorenes (Scheme 11.3). The consecutive [2+2+2] cycloaddihon of two types of tehayne provided a ladder-type silafluorene and a spirosilabi-fluorene (Schemes 11.4 and 11.5). 

In the intermolecular reaction of tetraynes, where two 1,6-diyne moieties were directly connected, with monoalkynes, CHIRAPHOS (2,3-bis(diphenylphosphino) butane) was the choice of chiral ligand, and axial chirality was enantiomericaUy generated between the formed benzene rings (Scheme 11.17). Hexaynes with a 1,3-diyne moiety also underwent an intramolecular [2-i-2-i-2] cycloaddition, and the Ir-xylylBINAP (2,2 -bis[di(3,5-xylyl)phosphino]-l,l -binaphthyl) catalyst induced an excellent enantiomeric excess (ee) (Scheme 11.18) [24]. 

Crossed-alkyne cyclotrimerizations between the diynes 580 and the monoalkynes 581 with a catalytic amount of RhClfPPhsls afforded substituted carbazoles 582. The high efficiency of the carbazole formation could be rationalized by the conformational restrictions present in the diynes 580 (561) (Scheme 5.27). 

Reaction of carbanions with dialkynic ketones, the so-called skipped diynes, can produce pyranones through an initial Michael condensation. It should be noted however that diynones are vulnerable to attack at several sites and that mixed products can be formed. Addition of the anions derived from diethyl malonate and ethyl cyanoacetate to hepta-2,5-diyn-4-one (313 R1 = Me) gives the pyranones (314 R2 = C02Et or CN Scheme 91) (74JOC843). The former carbanion reacts similarly with the diynone (313 R1 = Bun) (68T4285). The second alkyne moiety appears to have little effect on the course of the reaction, which parallels the synthesis of pyranones from monoalkynic ketones. 

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). 

Intramolecular [2+2+2] cyclotrimerizations of diynes and triynes possessing heteroatom tethers furnish benzoheterocycles. The cyclization of triynes 88 using the Grubbs catalyst 76 proceeds via cascade metathesis as shown in Eq. (35) to yield a tricyclic product 89 [88]. This novel type of catalytic alkyne cyclotrimerization can be applied to the cycloaddition of 1,6-diynes with monoalkynes [89]. 

Whereas both Pauson-Khand based reactions presented above are intramolecular processes, a bimolecular route to [5,5,6]-tricyclic compounds is also available [37]. Indeed, it was shown that diynes could be reacted with monoalkynes using a catalytic amount of Co2(CO)s. In this way, compound 27 and phenylacetylene were converted into tricyclic product 28 in 68% yield (Scheme 13). Although high temperature and pressure of CO were required, compound 28 was obtained as a single regio- and diastereomer. 

The results presented above indicate that the Zr-promoted bicyclization reactions of enynes and diynes constitute novel and attractive synthetic methods. The corresponding reaction of dienes remains to be developed. Somewhat unexpectedly, the reactions of monoalkynes and monoalkenes can, in many cases, be highly pair selective and regioselective. Many aspects of these reactions also need to be further developed. Besides being attractive from the viewpoint of organic synthesis, the chemistry of ZrCp2 provides a number of novel structural and mechanistic features that broaden the horizon of organometallic chemistry. 

In the presence of dicarbonylbis(triphenylphosphine)nickel(0), the diyne 252 reacts with monoalkynes to give quinones 253, and in the presence of nickel tetracarbonyl, 252 dimerizes to give 254 in 80% yield along with a small amount of... 

Ni-alkyne bonding consists of contributions from both the 77, 7t- and cr,diyl tautomers. This bonding picture helps visualize the insertion reactions with alkynes, alkenes, and CO that result in the formation of metallacycles. Thanks to such insertion reactions, Ni-alkyne species are active intermediates in a number of catalytic applications such as alkyne oligomerization, carbonylation, and insertion of heterocumulenes such as CS2 and GO2. For example, a recent example of a C02-fixation reaction involved the stoichiometric, alkylative or arylative carboxylation of alkynes to give a,(3- and / ,/ -unsaturated carboxylic acids. Ni(0)-alkyne complexes have also been used as pre-catalysts in the addition of hydrosilanes to alkynes. In most cases, monoalkynes react to give the products of m-addition, whereas diynes produce enynes (1,2-addition), allenes (1,4-addition), or 1,3-butadienes (1,2,3,4-addition). ... 

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 Cp RuCl(cod)-catalyzed reaction of 1,6- and 1,7-diynes in the presence of monoalkynes led to a [2-f2-f2] cycloaddition. Various substituted benzenes were thus produced in good yields [18-36]. The cycloaddition of unsymmetrical diynes usually favors meta-substituted products by means of judicious choice of substituents as inEq. (11) [18]. 

Examples of improved chemoselectivity by immobilized diyne on a solid-support [19-21] or of improved reactivity of less reactive alkynes by use of microwave [21-24] were recently described. A wide variety of diynes and monoynes containing functional groups were applied to this reaction in the past decade. Arylboronates [25, 26] and diiodo benzenes [27, 28] [Eq. (12)] were thus obtained and involved in further transformatiOTis. Several types of compounds able to present biological activities could also be synthesized such as benzo-fused lactams and lactones [23, 29] [Eq. (13)], phtalans [19], indanones [20], indanes [21], phenanthridines [22], benzoproline and tetrahydroisoquinoline derivatives [30, 31], C-arylglycosides and C-arylribosides [32-35]. Recently, this ruthenium-catalyzed [2+2+2] cycloaddition between a diyne and a monoalkyne was also used as reaction step in total syntheses [20, 23, 24, 36]. 

Partially intramolecular reactions have the advantage of using readily accessible diynes and monoalkynes as substrates. However, problems with chemo- and regios-electivity remain. Facile dimerization of the diynes is a serious obstacle that must be overcome by using a large excess of the monoalkyne component. In 20(X), Yamamoto... 

Young et al. developed solid-supported [2 - - 2 - - 2] cycloadditions in pursuit of a library synthesis using immobilized diyne substrate 55 with monoalkynes in the presence of catalyst 6 (Table 3.10) [42], This method avoids competitive selfcycloaddition of the expensive diyne substrate. In addition, immobilization facilitates the separation of the cross-cycloadducts from the catalyst, unreacted reagents, and... 

However, in this case the electron-rich 1-methoxypropyne was used as the monoalkyne. First, 108 was converted into yne-ynamide 109 by three steps, including a Sonogashira reaction with trimethylsilylacetylene and the ynamide formation based on the alkynyliodonium salt 105. Yne-ynamide 109 was then alkylated with iodopen-tane, and subsequent desilylation with TBAF provided the diyne 110 (44% yield over two steps). The key cyclotrimerization of diyne 110 with 1-methoxypropyne was carried out in toluene at room temperature in the presence of 10 mol % of Wilkinson s catalyst and afforded chemo- and regioselectively carbazole 111 (82% yield, isomer... 

STEREOCHEMICAL ASPECT OF INTRAMOLECULAR AND INTERMOLECULAR REACTIONS OF DIYNES WITH MONOALKYNES... 

Intermolecular coupling of a monoalkyne and diyne ethers and amines with ort o-substituted aryl groups in acetylenic branches resulted in tetraaryl compound with two axial chiralities. Thus, in a reaction of such symmetric diynes with symmetric monoalkynes chiral compounds with Cl symmetry were obtained (Scheme 2.19) [61]. 

Table 2.3 Intermolecular reaction of symmetrical diynes and monoalkynes.

The reaction of diyne 2.59 with but-2-yn-l,4-diol 2.60b or with but-2-yn-l-ol 2.60c gave axially chiral diol 2.61b and monool 2.61c (Scheme 2.21). The reaction proceeded effectively even at room temperature in 1,2-dimethoxyethane [61, 62]. Monoalkynes including a nitrogen atom 2.60d,e also react well in the coupling reaction with diyne to form axially chiral amines and amino alcohols 61d,e with excellent diastereoselectiv-ity and enantioselectivity (Scheme 2.22) [61, 62],... 

Shibata, T., Arai, Y., Takami, K. et al. (2006) Iridium-catalyzed enantioselective [24-24-2] cycloaddition of diynes and monoalkynes for the generation of axial chiralities. Advanced Synthesis Catalysis, 348(16-17), 2475-2483. 

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