Cobalt catalysis cycloaddition

Related co-cyclotrimerizations of two alkyne molecules with limited isocyanates have also been achieved using cobalt and nickel catalysts. With respect to intramolecular versions, two examples of the cobalt(I)-catalyzed cycloaddition of a,m-diynes with isocyanates have been reported to afford bicyclic pyri-dones only in low yields, although 2,3-dihydro-5(lff)-indolizinones were successfully obtained from isocyanatoalkynes and several silylalkynes with the same cobalt catalysis [19]. On the other hand, the ruthenium catalysis using Cp RuCl(cod) as a precatalyst effectively catalyzed the cycloaddition of 1,6-diynes 21 with 4 equiv. of isocyanates in refluxing 1,2-dichloroethane to afford bicyclic pyridones 25 in 58-93% yield (Eq. 12) [20]. In this case,both aryl and aliphatic isocyanates can be widely employed. 

For example, access to axial chirality can be realized under cobalt catalysis using a chiral cobalt(I) complex [4], However, the use of chiral iridium and rhodium species dramatically improved the scope and enantioselectivities obtained for this cycloaddition. Tanaka and coworkers synthesized an atropoisomeric diphosphine oxide in 97% ee, by treatment of the suitable hexayne with [Rh(cod)2]BF4 in the presence of (7 )-TolBINAP as source of chirality (double [2-1-2-1-2] cycloaddition). Subsequent reduction afforded an axially chiral bidentate ligand as a single enantiomer (Scheme 7.1) [5]. 

An early contribution to use of the transition-metal-catalyzed pyridine formation reaction was the synthesis of vitamin Be (124) via the crossed-cyclotrimerization reaction of the bis-stannylated diyne 122 with acetonitrile under cobalt catalysis (Scheme 7.26) [36a andb]. The underlying crossed [2 - - 2 - - 2] cycloaddition reaction here provided the fused pyridine 123 in 76% yield after a regioselective destannylation effected by treatment of the cycloaddition product with aluminum oxide. 

Originally, the pyridine construction reaction was based on cobalt catalysis and restricted to the use of acetonitrile or alkyl nitriles as one of the cycloaddition partners. However, recent advancements in this area have led to the development of certain ruthenium or rhodium catalysts, allowing the use of methylcyanoformate as an electron-deficient nitrile component in crossed [2 - - 2 - - 2]-cycloaddition reactions [39]. From the point of view of applications, the use of methylcyanoformate in transition-metal-catalyzed pyridine formation reaction is quite beneficial because the ester moiety might serve as a functional group for further manipulations. It might also serve as a protective group of the cyanide moiety, because cyanide itself cannot be used in this reaction. These considerations led to the design of a quite flexible approach to substituted 3-(130)- and y-carbolines (131) based on transition-metal-catalyzed [2 -f 2 -I- 2] cycloaddition reactions between functionalized yne-ynamides (129) and methylcyanoformate (Scheme 7.28) [40]. 

Nevertheless, the application of alkoxy-functionalized 1,3-dienes is of increasing interest. 1-Alkoxy-functionalized 1,3-butadienes led directly to arene derivatives such as 22 via the cycloaddition/elimination route (Scheme 13.12) [13]. The arene is formed under the reaction conditions of cobalt catalysis upon elimination of trimethyl-silanol from the labile dihydroaromatic intermediate. When 2-alkoxy-functionalized 1,3-butadienes are employed, 3,4-disubstituted phenol derivatives such as 23 are readily available by DDQ oxidation of the dihydroaromatic intermediate. The DDQ oxidation conditions led in several cases to direct desilylation of the enol ether or the desilylation takes place during column chromatography on (nondeactivated) silica gel. 

Lewis-acid catalysis is effective in intermolecular as well as intramolecular /zomo-Diels-Alder reactions. Thus, complex polycyclic compounds 93 have been obtained in good yield by the cycloaddition of norbornadiene-derived dienynes 92 by using cobalt catalyst, whereas no reaction occurred under thermal conditions [91] (Scheme 3.18). 

Cycloadditions Several metals are known to trigger stereoselective [2-I-2-I-2] cycloaddition of polyunsaturated systems [3] and this approach has been applied to different types of unsaturated substrates. In this general overview, most cited examples will focus on cobalt, nickel, and rhodium catalysis. 

Toselli, N., Martin, D., Achard, M., Tenagha, A., Biirgi, T., Bnono, G. (2008). Enantiose-lective cobalt-catalyzed [6+2] cycloadditions of cycloheptatriene with alkynes. Advanced Synthesis Catalysis, 350, 280-286. 

The [2 -I- 2 -I- 2] cycloaddition reaction can give rise to chiral compounds, especially biaryls [3q]. Control of the enantioselectivity in such transformations is of prime importance, notably because biaryls can be used as ligands in asymmetric catalysis. This topic is covered in detail in Chapter 9. Nowadays, cobalt still looks like a poor relation in this field, which is largely dominated by rhodium. Nevertheless, a report from Heller et al. shows for the first time that phosphorus-bearing axially chiral biaryls 9 can be formed by enantioselective benzene formation using the neomenthyl-indenyl cobalt complex II as a catalyst (Scheme 1.3) [7]. Good yields... 

The same year, Gandon et al. reported the synthesis of fused arylboronic esters 36 via cobalt(0)-mediated cycloaddition of alkynylboronates 33 with diynes 35 (Scheme 1.11) [22], The boronate is first reacted with Co2(CO)g at room temperature for 4 h to generate the corresponding dicobaltatetrahedrane 34. The diyne is then added and the mixture is refluxed for 2 h. To show the utility of the products, one of them was treated with phenyl iodide under Pd catalysis to give 37. Complementary to these investigations, Ru-catalyzed [2 - - 2 - - 2] cycloaddition of tethered alkynyl-boronic esters with alkynes was reported [23]. In this case, the borylated arene could not be isolated but was converted directly in situ by Suzuki-Miyaura coupling. 

Although in principle the thermal [2-I-2-I-2] cycloaddition process is allowed by orbital symmetry rules, there are problems with the entropy component, which may be overcome by using transition metal catalysis. This approach (Scheme 2.35) is one of the most convenient for the synthesis of pyridines 2.100. Metal-induced cycloaddition of two alkyne and one nitrile molecules has been described in general reviews of cycloaddition reactions [3,4]. However in some reviews on heterocycles the nitriles are considered as equivalent to alkyne in the [2+2+2] cyclotrimerization reaction [76], in particular, for the synthesis of pyridines and pyridinones in the reactions catalyzed by cobalt, ruthenium, titanium, and zirconium. 

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