Cycloaddition of 1,6-diynes

The NHC-nickel catalytic system is also useful in the synthesis of pyridones 48. The [2h-2h-2] cycloaddition of diynes 44 and isocyanates 47 affords a wide range of pyridones 48 in excellent yields in presence of [Ni(COD)2]/SIPr catalytic system (Scheme 5.14) [18]. 

Scheme 5.14 [2+2+2] Cycloaddition of diynes and isocyanates in presence of [Ni(COD) ]/SIPr catalytic system...

Ruthenium(ll)-catalyzed cycloadditions of diynes with bicycloalkenes illustrate the synthetic importance of ruthena-cyclopentatrienes as biscarbenoid intermediates.380 Reaction of 1,6-diyne 448 and biscyclic alkene 449 with ruthenium catalyst afforded a mixture of biscyclopropanation product 450 and cyclotrimerization product 451 (Scheme 113). 

Ikeda and coworkers351 performed [2 + 2 + 2] cycloadditions of diynes with a,ji-enones using NiCl2/Zn (1 10) as the catalytic couple. In these reactions, nickel dichloride... 

Nitrogen-based heterocycles can also be prepared through Ni/NHC-catalyzed cyclo addition reactions. For example, Ni/SIPr catalyzed the cycloaddition of diynes with isocyanates under the mildest conditions to date [26]. In particular, excellent yields of pyridones are obtained from diynes and isocyanates at room temperature using only 3 mol % catalyst. As shown in Eq. 8, a variety of diynes were subjected to these optimized conditions. Both aryl and alkyl isocyanates were readily converted to the respective 2-pyridone. Sterically hindered substrates appeared to have very little effect on the reaction, as excellent yields of product were obtained with bulky isocyanates and bulky diynes. 

In contrast to isocyanates, isothiocyanates have hardly been examined as cycloaddition components, because the strong coordination of organosulfur compounds frequently deactivates a catalytic species [21]. Some organoruthe-nium complexes, however, recently proved to be efficient catalysts for the formation of carbon-sulfur bonds [21]. The catalytic cycloaddition of diynes with isothiocyanates was also successfully achieved using Cp RuCl(cod) as a precatalyst [22]. Importantly, the cycloaddition took place at the C=S double bonds of the isothiocyanates to afford thiopyranimines 26 (Eq. 13). This reaction requires 10 mol % of the precatalyst as well as the diynes possessing a quarternary carbon center at the 4-position. When excess amounts of carbon disulfide were also employed in place of the isothiocyanates, a bicyclic dithiopyrone 26 [X is C(C02Me)2, Z is S] was obtained in 50% yield. 

Fused 2//-pyran-2-ones are formed in excellent yields and under mild conditions through a Ni-catalysed [2+2+2] cycloaddition of diynes and C02 <02JA15188>. Oxidative demetalation of 0i3-allyl)Mo complexes of pyran with pyridinium dichromate (PDC) introduces a carbonyl function at the allylic terminus offering access to dihydropyranones of high enantiopurity <02JOC5773>. 

Scheme 54 Cycloaddition of diynes with dienes in the synthesis of triquinanes. Tandem [2 + 2 + l]/[4 + 2] cycloadditions...

A catalytic, completely regioselective conversion of 4,4-dimethyl-2-pentyne (methyl-r-butylacetylene) to 2,5-di(r-butyl)-3,4-dimethylcyclopentadienone is mediated by (PhCN)2PdCl2. Other examples exist for early as well as late transition metals, and an isonitrile has been used as a CO equivalent in one Ni -based system as well, Finally, a heterogeneous catalytic intramolecular cycloaddition of diynes has been developed, leading to cyclopentadienones which either dimerize (Diels-Alder) or in certain cases may be trapped by nucleophiles (equation 10). °... 

A novel cycloaddition of diynes with aldehydes is catalyzed by the same metal system, giving rise to bicyclic a-pyrans after 1,5-hydrogen shifts. Yields of these sensitive compounds are remaritably high (equation 52). ... 

Scheme 39. Catalytic [2 + 2 + 2]-Cycloaddition of Diynes with (a) Alkynes, (b) Allenes, and (c) Alkenes...

Scheme 2-47. Asymmetric[2+2+2] cycloaddition of diynes with isocyanates. Typical procedur ...

The related cycloaddition of diynes with carbon dioxide has also been developed as an efficient entry to pyrones (Scheme 3-29). As observed with isocyanate couplings, initial reports described the use of phosphine complexes of Ni(0), " but more recent work with A-heterocyclic carbene ligands demonstrated considerably milder conditions and broader scope. " Additionally, the cycloaddition of diynes with nitriles efficiently proceeds to generate pyridine derivatives under similar conditions. ... 

The nickel-catalysed 2 + 2 + 2-cycloaddition of a 3-methyl-2-pyridyl aldimines with alkynes produced 1,2-dihydropyridine adducts in good yields. A key step in this transformation is the formation of aza-nickelacycle intermediates. The iron-catalysed 2 + 2 + 2-cycloadditions of alkyne nitriles with alkynes, in the presence of pyridyl bisimine ligands (95), formed substituted pyridines in good yields. The nickel-catalysed 2 + 2 + 2-cycloadditions of diynes and cyanamides have been investigated. The reactions have been shown to be regioselective, and cycloadducts are produced in good to excellent yields. ... 

Rhodium(I)-catalysed 2 + 2 + 2-cycloadditions of ene-allene (96) with allene (97) yielded trans-fused hydrindanes (98) and decalins with high regio- and stereo-selectivities (Scheme 31). A Ni-phosphine complex catalysed the 2 + 2 + 2- (g) cycloaddition of diynes with substituted ketenes to produce 2,4-cyclohexadienones in high yields. No decarbonylation products were observed. The chiral A-heterocyclic carbene-catalysed enantioselective 2 + 2 + 2-cycloaddition of ketenes with CS2 produced l,3-oxatian-6-ones in good yields and with high enantioselectivities. 2" ... 

Pyridine derivatives were prepared from a rhodium-catalyzed [2-I-2-1-2] cycloaddition of diynes and oximes (Scheme 18) (13CEJ2252).This reaction proceeds under mild conditions and complements the traditional approach. 

The chemo- and regioselectivity problems can be solved by the [2+2+2] cycloaddition of diynes with monoynes, although the accessible products are limited to bicyclic compounds. The [2+2+2] cycloaddition of diynes with monoynes has been applied to the synthesis of biologically active molecules and functional materials. The first application in the natural product synthesis was the dl-estrone synthesis using CpCo(CO)j as a catalyst. The [2+2+2] cycloaddition followed by the benzocyclobutane to ort/jo-quinodimethane rearrangement and intramolecular Diels-Alder reaction afforded a dZ-estrone precursor (Scheme 21.8) [11]. 

SCHEME 21.8 Co-catalyzed [2+2+2] cycloaddition of diyne with monoyne for synthesis of [Pg.591]

Additionally, several nickel-catalyzed systems for pyridines synthesis have also been developed by Louie and coworkers. In 2005, they reported that with Ni(COD)2 as the catalyst and carbene as the ligand, the cyclization can be carried out at room temperature (Scheme 3.23a) [51]. Both intramolecular and intermolecular reactions were proceeded well and the cycloaddition of an asymmetrical diyne afforded a single pyridine regioisomer. This catalytic system was extended to cyanamides as well [52], In their systematic studies, they found the in situ formed dimeric [Ni(IPr)RCN]2 from the reaction of Ni(COD)2, IPr, and nitrile are catalytically competent in the formation of pyridines from the cycloaddition of diynes and nitriles. X-ray analysis revealed that these species display simultaneous f- and 17 -nitrile binding modes. Kinetic... 

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