Cobalt-catalyzed Cyclization Reactions

The catalytic cyclotrimerization of alkynes to give substituted benzenes was investigated in supercritical water by the groups of Parsons [53a] and Dinjus [53b] using [CpCo(CO 2] as the catalyst. The reaction proceeded smoothly with 1-alkynes and phenylacetylene at T - 374 °C and p = 250 bar using substrate to catalyst ratios up to 35 1. The ratios of isomeric trisubstituted ben- 

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Wilfried Hess was born in Wiesbaden in 1979. He studied chemistry at the Philipps-University in Marburg and is currently a Ph.D. student working in the group of Prof. Hilt in the field of cobalt-catalyzed cyclization reactions. 

Organometallic reactions leading to condensed pyrans containing three or more rings have been achieved by cyclooligomerization processes and by intramolecular coupling. The former type of reaction is based on intramolecular trapping of o-xylylenes produced in cobalt-catalyzed cyclization... 

Fig. 60 Cobalt-catalyzed tandem reactions involving radical cyclizations...

Wakabayashi et al. introduced a very powerful mixed cobalt-catalyzed tandem reaction based on a radical cyclization followed by cross-couplings (Scheme 69) [187]. The reactive species is believed to be a 17-electron cobalt ate-complex, which would imdergo SET to yield an anion radical derived from 222, and thus a radical upon loss of bromide. The cobalt(l) complex gen-... 

In contrast, cyanoynamines react with phenyl isocyanate via an initial [2+2] cycloaddition reaction across the CM3 bond of the isocyanate to give a quinoline derivative Intramolecular cobalt catalyzed cyclization of alkynes and isocyanates was employed in the total synthesis of camptothein, an antitumor alkaloid. The key step of the synthesis involves the reaction of the acetylene group-containing isocyanate 185 with the acetylene derivative 186 to give 187. ... 

The cobalt-catalyzed reaction was studied by isolation of the lactones formed by hydrogenation and lactonization at higher temperatures (73). The hydroformylation was conducted at 140°C and 300 atm, followed by hydrogenation and cyclization at 200°-240°C, Eq. (33). 

The first rhodium-catalyzed reductive cyclization of enynes was reported in I992.61,61a As demonstrated by the cyclization of 1,6-enyne 37a to vinylsilane 37b, the rhodium-catalyzed reaction is a hydrosilylative transformation and, hence, complements its palladium-catalyzed counterpart, which is a formal hydrogenative process mediated by silane. Following this seminal report, improved catalyst systems were developed enabling cyclization at progressively lower temperatures and shorter reaction times. For example, it was found that A-heterocyclic carbene complexes of rhodium catalyze the reaction at 40°C,62 and through the use of immobilized cobalt-rhodium bimetallic nanoparticle catalysts, the hydrosilylative cyclization proceeds at ambient temperature.6... 

A [2+2+2] cyclization reaction of acetylenes and nitriles leads to the formation of furo[3,4-r]pyridines under cobalt-catalyzed conditions (Scheme 11) <2005SL1188>. 

Other metal salts, such as Cr3+, Rh3+ or Ru3+ derivatives, catalyze the cyclization of dihydrobilin to porphyrin [63] differently from copper, these metals afford the metal-free ligand and this seems to be a suitable route for the preparation of porphyrins with acid-labile substituents, which in the previous method suffer during the removal of the copper atom. On the other hand, dihydrobilin also cyclizes to porphyrin when heated in 1,2-dichlorobenzene or when treated with bases although in lower yields [3, 8, 10]. The presence of nickel or cobalt salts seems to be necessary to drive the cyclization reaction towards the formation of the octadehydrocorrin structure. 

Oshima provided a number of examples of cobalt-catalyzed tandem radical 5-exo cyclization/cross-coupling reactions (Fig. 59, Table 4). Allyl a-haloaldehyde... 

Fig. 59 Low-valent cobalt-catalyzed radical cyclization/Kumada coupling reactions...

A tandem radical 5-exo cyclization/radical addition/allylic substitution reaction was subsequently described [292]. Allylic ot-bromo acetal 242b cyclized cobalt-catalyzed. Addition to diene 245 and subsequent coupling with coformed organocobalt(I) species generates an allylcobalt complex, which undergoes reductive elimination to cyclic product 246 in 93% yield (cf. Fig. 56). 

Fig. 98 Cobalt-catalyzed alkoxyl radical cyclization reactions...

Estrones. An A —> BCD approach to estrones involves a cobalt catalyzed intramolecular 2 + 2 -y 2] cycloaddition of the enediyne 1 to form the B, C. and D rings in one step. The high stereoselectivity suggests that the cyclization involves a Dicls-Alder-type reaction of the vinyl group with a cobaltacyclopentadiene formed by coupling of the two alkyne units. The homoannular diene obtained on demetalation is isomcrized easily to the diene 3. 

Starting from optically active nitriles, Botteghi and co-workers [32] have applied the cobalt-catalyzed reaction for the prepartion of optically active 2-substituted pyridines (eq. (8)). The chiral center is maintained during the alkyne-nitrile co-cyclization reaction. This reaction has recently been extended to the synthesis of bipyridyl compounds having optically active substituents [33] and provides an access to chiral ligands of potential interest in transition metal-catalyzed asymmetric synthesis. 

The catalytic reaction may also be ctirried out using two different alkynes. For example, the co-cyclization of acetylene and propyne with acetonitrile yields a mixture of dimethylpyridines (lutidines) in addition to a-picoline and the isomeric collidines. The co-cyclization, however, turned out to be nonselective. For experimental details see [5 g]. The cobalt-catalyzed co-cyclization of benzonitrile and acetylene at 77 -Cp-cobalt cod gives 2-phenylpyridine in high yield. 

The cobalt-catalyzed co-cyclization of alkynes with heterofunctional substrates is not limited to nitriles. / -Cp-cobalt half-sandwich complexes are capable of co-oligomerizing alkynes with a number of C=C, C=N, C=0, or C=S bonds in a Diels-Alder-type reaction. Chen has observed that these cycloadditions are best performed in the presence of a small amount of ketones or esters [48]. This modified cycloaddition may be used for the formation of dihydroindole systems at the 7 -Cp-cobalt catalyst (eq. (17)). 

The regiochemical product distribution of the co-cyclization of two or three different alkynes occurs statistically. In some cases carefully controlled reaction conditions allow isolation of a main product from mixed cyclotrimerizations. For example, l,2,3,4-tetraphenyl-5,6-diethylbenzene can be obtained from cobalt-catalyzed reaction of tolane and 3-hexyne in good yield [62]. The first example of an intermolecular, regiospecific cross-benzannulation reaction catalyzed by Pd(PPh3)4 was reported by Yamamoto [63]. The reaction of 2-alky 1-but-l-ene-3-yne with disubstituted diynes leads exclusively in high yields to... 

Instead of a second or third alkyne, an alkene C=C double bond may be incorporated into the cyclotrimerization reaction. Iron [65], rhodium [66], nickel [67], palladium [68], or cobalt [69] catalysts have been used to form cyclohexa-dienes. However, the preparative use of this catalytic co-cyclization is disturbed by consecutive side reactions of the resulting dienes such as cycloaddition or dehydrogenation. Itoh, Ibers and co-workers [70] have reported the straight palladium-catalyzed co-cyclization reaction of C2(C02Me)2 and norbomene (eq. (24)). 

An interesting cyclodimerization of internal alkynes is apparently proceeding via metallation in the propargylic position, followed by an insertion of a second alkyne molecule, intramolecular carbometallation and o-bond metathetical protonolysis (Fig. 24) [65]. The reaction is slow even at elevated temperatures and the insertion is not regioselective in case of unsymmetrical alkynes. More hindered substituents such as Bu are not tolerated as the reaction stops at the metallation step. The reaction is more of a fundamental interest, as the cyclization pattern is different from the most common [2 + 2] route of existing protocols of transition-metal (in particular cobalt)-catalyzed alkyne cyclodimerization, which are significantly more versatile and synthetically applicable [194],... 

Steroid synthesis. The cobalt-catalyzed cooligomerization of a 1,5-hexadiyne (1) with bis(trimethylsilyl)acetylene (2) has culminated in a synthesis of the estra-trienone 4. The cyclization results in formation of the desired Irons, anti, trans arrangement of the B, C, and D rings, probably for steric reasons. The reaction... 

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