Unsymmetrical diynes

The organoborate intermediates can also be generated from alkenylboronic esters and alkyllithium or Grignard reagents, or from ttialkylboranes and alkenyllithium compounds. Conjugated symmetrical and unsymmetrical diynes (289—291), stereochemically pure 1,3-dienes (292,293), and 1,3-enynes (294) including functionali2ed systems can be prepared (289,295). 

As for alkenes, the rate of hydrozirconation of alkynes decreases with increasing substitution on the alkyne. An unsymmetrical diyne reacts with 1 preferentially at the less-substituted triple bond [85]. 

Recently, Marino et al. reported a Cadiot-Chodkiewicz cross-coupling reaction of bulky trialkylsilyl-protected alkynes with 1-bromoalkynes in aqueous amine to form a variety of unsymmetrical diynes in good yields (75 95%) (Eq. 4.23).44... 

In the reaction of an unsymmetrical diyne with 9, the boryl group is introduced regioselectively to the terminal acetylenic bond (Equation (100)). 

The Sonogashira reaction is of considerable value in heterocyclic synthesis. It has been conducted on the pyrazine ring of quinoxaline and the resulting alkynyl- and dialkynyl-quinoxalines were subsequently utilized to synthesize condensed quinoxalines [52-55], Ames et al. prepared unsymmetrical diynes from 2,3-dichloroquinoxalines. Thus, condensation of 2-chloroquinoxaline (93) with an excess of phenylacetylene furnished 2-phenylethynylquinoxaline (94). Displacement of the chloride with the amine also occurred when the condensation was carried out in the presence of diethylamine. Treatment of 94 with a large excess of aqueous dimethylamine led to ketone 95 that exists predominantly in the intramolecularly hydrogen-bonded enol form 96. 

A detailed study on the catalytic use of Pd/TPPTS catalyst in aqueous Sonogashira couplings revealed, that it is possible to obtain unsymmetrical diynes with moderate to good yields in aqueous methanol, with Cul as promoter and Et2NH as base (Scheme 6.18) [44]. The same authors describe a short synthesis of Eutypine, which is an antibacterial substance isolated from the culture medium of Eutypa lata. The fungus E. lata is held responsible for a vinyard disease known as eutyposis, so obviously this synthesis is of great interest. 

When an unsymmetrical diyne is used, two regjoisomers of ortho and meta isomers are formed. Then, by choosing the bidentate phosphorus ligand (DPPE or DPPE (l,l -bis(diphenylphosphino)ferrocene), the ratio of their formation could be controlled from 1 4 to 7 1 (Scheme 11.2) [12]. 

Sequential treatment of 00-bromoalkyl triflates with an alkyllithium at 0°C followed by addition of a second alkynyllithium and Nal and heating the reaction mixture gave unsymmetrical diynes in one-pot in good yields. This methodology was used to stereoselectively transform these diynes to diene pheromones such as Z,Z)- and... 

A similar coupling of alkynyliodonium tosylates 132 with dialkynylcuprates 134 leads to conjugated diynes 135 (Scheme 55) [114,115]. This method can be used for the preparation of unsymmetrical diynes in moderate yield. Recently, this coupling was employed in the synthesis of various liquid-crystalline diaryl-diacetylenes [115]. 

Lithium dialkynylcuprates behave similarly with alkynyliodonium tosylates and lead to conjugated diynes (equation 133)109. Unsymmetrical diynes can be prepared with moderate selectivity by this method, although they are accompanied by symmetrical diynes derived from the alkynyliodonium component. The treatment of lithium diphenyl- and dialkylcuprates with alkynyliodonium tosylates has also been investigated and affords alkyl- and phenyl-substituted alkynes (equation 134)109. 

A highly electron-deficient carbon-oxygen double bond can also participate in the cyclocotrimerization with diynes under ruthenium catalysis. The cydoaddition of commercially available diethyl ketomalonate with the unsymmetrical diynes 22 proceeded at 90 °C in the presence of 5-10 mol% 17 (Scheme 4.22) [54]. The expected... 

Unsymmetrical diynes can be prepared by Cadiot-Chodkiewicz coupling ... 

The ability of water to attack the ruthenium-carbon double bond suggested that the ruthenacyclopentadiene might add water as depicted in Scheme 1.4. Remarkably, heating a tethered diyne in aqueous acetone to 60 °C in the presence of the trisacetonitrile complex 16 gave a nearly quantitative yield of the hydrated cyclization product as depicted in Equation 1.29 [26], Unsymmetrical diynes showed exquisite regioselectivity wherein the water attacked the least sterically hindered alkyne carbon (Equation 1.30). 

Shanmugasundaram et al. reported that the nickel-catalyzed [2 + 2 + 2]-cycloaddition of the 1,6-diynes 121 with phenylallene gave the 1,3-dihydroisoben-zofuran derivatives 122 in good yields (Scheme 42).119a The reaction of the unsymmetric diyne 121b afforded only the meta-isomer 122b. 

Phospholes prepared in the original report as well as by later users of this method are shown in Table 12. In addition to bases, the reaction may be promoted by metal salts and by free radicals <7lT5523>. Markl had employed only symmetrical diynes in the reaction, but unsymmetrical diynes work quite well <71JA6205>. 

It is used for preparing cationic COD-Rh complexes with phosphine ligands for enantioselective [2+2+2] cycloaddition of unsymmetrical diynes with styrene and noibomene derivatives to yield bi- and tetra-cyclic products with good ( 50%) to very good (>90%) enantiomeric enrichment [Shibata et al. Tetrahedron 63 12853 2007], for hydrogenation [Nagel et al. Chem Ber 119 3326 1986, Ojima et al. Tetrahedron 45 6901 1989, Sawamura et al. J Am Chem Soc 117 9602 1995], and for hydrosilylation [Takeuchi et al. J Org Chem 60 3045 1995]. 

Palmer et al. [184] prepared a stable dehydro[14]annulene by reaction of a l-sUyl-2-stannylethyne and a bromoaromatic functionality. Lukevics et al. [185] synthesized unsymmetrical diynes by reactions between alkynylstannanes and terminal bromoalkynes. 

Takeuchi and coworkers reported an iridium-catalyzed cycloaddition of a,o -diynes and nitriles to give pyridines in 2012 [57]. With [Ir (cod)Cl]2/DPPF or BINAP as the catalytic system, pyridines were formed effectively (Scheme 3.24). A wide range of nitriles (aliphatic and aromatic nitriles) can be applied and reacted smoothly with Q ,a -diynes to give the pyridines. In the case of unsymmetrical diyne bearing two different internal alkyne moieties, high regioselectivity can be achieved which can be explained by the different reactivities of the a-position in iridacyclopentadiene. Terpyridine and quinquepyridine were prepared as well. [Ir(cod)Cl]2/chiral diphosphine catalyst can be applied to enantioselective synthesis. Kinetic resolution of the racemic... 

Some interesting points emerged from this systematic study (i) steric hindrance on the diynes only had a little influence on the catalytic process (ii) when starting from unsymmetrical diynes, larger substituents were introduced in the 3-position of the formed pyridone (iii) under dilute conditions, unsymmetrical diynes were converted into pyridones without telomerization to aromatic by-products and (iv) aryl- as well as alkyl-isocyanates were reactive however, electron-poor arylisocyanate required a higher reaction temperature (80 °C). 

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]. 

The cyclization of thienyl-substituted diacetylenes with hydrogen sulfide or sodium sulfide is also a very successful method for the synthesis of oligothiophenes. The key point here is the synthesis of the precursor diynes. Symmetrical diacetylenes can be obtained by the oxidative coupling of acetylenes with copper(I) or copper(II) salts ( Glaser, Hay, or Eglington coupling ). The synthesis of unsymmetric diynes proceeds best via the Cadiot-Chodkiewicz procedure in which an acetylene is reacted with an acetylic halide in the presence of copper(I) salts [117]. Therefore, thienyl-substituted acetylenes and bromoacetylenes are important starting materials. 

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