Cobalt-mediated reactions

In 1996, Malacria et al. [139] reported on cobalt-mediated reactions of the related allenynes. Heating the allenyne 222 in the presence of cpCo(CO)2 accompanied by a photochemical activation of this organometallic compound delivered the cross-conjugated trienes 223 (Scheme 15.71). The second triple bond present in the substrate did not participate in the reaction, underlining the higer reactivity of the allene unit. 

Cyclizing ca-chloro Reissert compound 136 gives rise to tricyclic lactam 137 (72JHC541). In a study of the cobalt-mediated reaction of pyridones with alkynes, in the case of the N-hexynyl compound, C-H activation with... 

Figure 4-47. A cobalt-mediated reaction of methyl thiocyanate.

A cobalt-mediated reaction of dioxabicyclo[3.2.2]nonane 287 furnishes the dihydropyranyl pyridazine derivative 288 in moderate yield (Scheme 73) <2003JOC7009>. 

In the laboratory of S.L. Schreiber, the total synthesis of (+)-epoxydictymene was accomplished by the tandem use of cobalt-mediated reactions as key steps. The eight-membered carbocycle was formed via a Nicholas reaction, while the five-membered ring was annulated by the Pauson-Khand reaction. Several P.-K. conditions were explored and the best diastereoselectivity was observed when NMO was used as a promoter. The annulated product was isolated as an 11 1 mixture of diastereomers. 

Jamison, T. F., Shambayati, S., Crowe, W. E., Schreiber, S. L. Tandem Use of Cobalt-Mediated Reactions to Synthesize (+)-Epoxydictymene, a Diterpene Containing a Trans-Fused 5-5 Ring System. J. Am. Chem. Soc. 1997,119,4353-4363. 

There are several examples known where methylenecyclopropanes have been employed as cosubstrates in reactions of the Khand—Pauson type. Generally, this cobalt-mediated reaction is performed with hexacarbonyldicobalt complexes of alkynes, preferably strained alkenes such as norbornene or cyclobutene, and carbon monoxide to produce cyclopent-2-enones. Stoichiometric amounts of cobalt (in the form of the alkyne complexes) are normally needed. Methylenecyclopropane (1) can be employed as the strained alkene and reacts with a variety of alkynes to yield spiro-fused products. Silica gel or zeolites function as promoters of the reaction, giving rise to improved yields. ... 

The cobalt-mediated reaction of diphenylmethyl(dibromo-methyl)silanes with trimethylsilylmethylmagnesium chloride yields 1,2-disilylethenes in a regio- and stereoselective fashion (eq 26). The reaction is applicable to the synthesis of... 

Jamison TF, Shambayati S, Crowe WE, Schreiber SL. Tandem use of cobalt-mediated reactions to synthesize (+)-epoxydictymene, a diterpene containing a transfused 5-5 ring system. J. Am. Chem. Soc. 1997 19 4353 363. 

The total synthesis of ( )-estrone [( )-1 ] by Vollhardt et al. is a novel extension of transition metal mediated alkyne cyclotrimeriza-tion technology. This remarkable total synthesis is achieved in only five steps from 2-methylcyclopentenone (19) in an overall yield of 22%. The most striking maneuver in this synthesis is, of course, the construction of tetracycle 13 from the comparatively simple diyne 16 by combining cobalt-mediated and ort/io-quinodimethane cycloaddition reactions. This achievement bodes well for future applications of this chemistry to the total synthesis of other natural products. 

Polymerization employing Co complexes as catalysts or else polymers incorporating functionality that includes Co ions represent aspects of polymerization reactions of interest here. Cobalt-mediated free-radical polymerization of acrylic monomers has been reviewed.55 Co11 porphyrins act as traps for dialkylcyanomethyl radicals.1098 Alkyl complexes of Co(TMesP)... 

Under the conditions of the cobalt-mediated carbonylative A-oxide-promoted cocyclization (Pauson-Khand reaction) at room temperature, compound 547 provides exocyclic 1,3-diene 548 as the major product (>98%) together with only traces of the corresponding carbonylative product 549. Owing to the relative instability of the diene, it is more efficient to perform a one-pot cobalt cyclization/Diels-Alder process after A-oxide-promoted cyclization of the cobalt complexes. Compound 550 is obtained as a single diastereomer in 39% overall yield if MTAD is used as a dienophile (Scheme 90) <2003JOC2975>. 

A somewhat related process, the cobalt-mediated synthesis of symmetrical benzo-phenones from aryl iodides and dicobalt octacarbonyl, is shown in Scheme 6.49 [100]. Here, dicobalt octacarbonyl is used as a combined Ar-I bond activator and carbon monoxide source. Employing acetonitrile as solvent, a variety of aryl iodides with different steric and electronic properties underwent the carbonylative coupling in excellent yields. Remarkably, in several cases, microwave irradiation for just 6 s was sufficient to achieve full conversion An inert atmosphere, a base or other additives were all unnecessary. No conversion occurred in the absence of heating, regardless of the reaction time. However, equally high yields could be achieved by heating the reaction mixture in an oil bath for 2 min. 

The asymmetric synthesis of allenes via enantioselective hydrogenation of ketones with ruthenium(II) catalyst was reported by Malacria and co-workers (Scheme 4.11) [15, 16]. The ketone 46 was hydrogenated in the presence of iPrOH, KOH and 5 mol% of a chiral ruthenium catalyst, prepared from [(p-cymene) RuC12]2 and (S,S)-TsDPEN (2 equiv./Ru), to afford 47 in 75% yield with 95% ee. The alcohol 47 was converted into the corresponding chiral allene 48 (>95% ee) by the reaction of the corresponding mesylate with MeCu(CN)MgBr. A phosphine oxide derivative of the allenediyne 48 was proved to be a substrate for a cobalt-mediated [2 + 2+ 2] cycloaddition. 

An allene is a very promising unsaturated partner in cobalt-mediated [2 + 2 + 2]-cycloaddition reactions. Exposure of an allenediyne to a stoichiometric amount of CpCo(CO)2 in boiling xylenes under irradiation for 5 h furnishes red-brown complexes in 42% isolated yield (Scheme 16.76) [84—87]. Treatment of a 7 3 mixture of the two diastereomers thus obtained with silica gel provides an oxygen-sensitive cobalt-free tricydic compound. 

A cobalt-mediated formal Alder ene reaction of an allenyne takes place to give a mixture of adducts and ( 4-cycloliexadiene)cobalt complexes (Scheme 16.77) [88], The reaction may proceed via coordination and ensuing jt-allyl complex formation. 

Scheme 16.77 Cobalt-mediated formal Alder ene reaction of an allene.

The cobalt mediated homo Diels-Alder reaction of norbomadiene (560) with phenyl acetylene (568a), affording a phenyl substituted deltacyclene, demonstrated the potential of low-valent cobalt complexes as catalysts332. Lautens and coworkers327 extended the scope of this reaction and were able to synthesize a wide range of substituted deltacyclenes from alkynes 568 (equation 164, Table 33). The low-valent cobalt or cobalt(O) species to be used was prepared in situ by reduction of Co(acac)3 with Et2AlCl. Monosubstituted... 

Cobalt, as its CpCo(CO)2 complex, has proven to be especially suited to catalyze [2 + 2 + 2] cycloadditions of two alkyne units with an alkyne or alkene. These cobalt-mediated [2 + 2 + 2] cycloaddition reactions have been studied in great detail by Vollhardt337. The generally accepted mechanism for these cobalt mediated cycloadditions, and similar transition metal mediated cycloadditions in general, has been depicted in equation 166. Consecutive co-ordination of two triple bonds to CpCo(CO)2 with concomitant extrusion of two molecules of carbon monoxide leads to intermediates 578 and 579 via monoalkyne complex 577. These react with another multiple bond to form intermediate 580. The conversion of 578 to 580 is said to be kinetically favored over that of 579 to 580. Because intermediates like 580 have never been isolated, it is still unclear whether the next step is a Diels-Alder reaction to form the final product or an insertion to form 581. The exact circumstances might determine which pathway is followed. 

As indicated in Chapter 8, the production of alkanes, as by-products, frequently accompanies the two-phase metal carbonyl promoted carbonylation of haloalkanes. In the case of the cobalt carbonyl mediated reactions, it has been assumed that both the reductive dehalogenation reactions and the carbonylation reactions proceed via a common initial nucleophilic substitution reaction and that a base-catalysed anionic (or radical) cleavage of the metal-alkyl bond is in competition with the carbonylation step [l]. Although such a mechanism is not entirely satisfactory, there is no evidence for any other intermediate metal carbonyl species. 

Typically, the reactions are carried out using a controlled potential, with the potential set to a value that allows the selective reduction of Co(III) in the presence of the alkyl halide and Michael acceptor [26]. Only 1-20 mol % of the cobalt mediator is needed. The reactions are conducted in a medium in which lithium perchlorate... 

Some of the most striking examples for an intramolecular Pauson-Khand reaction involving a tetrasubstituted double bond are the cobalt-mediated cyc-lizations of bicyclopropylidene derivatives 234 leading to the interesting spirocyclopropanated tricyclic products 235. The successful cyclizations even of the trimethylsilyl-substituted enynes 234 demonstrate the unique reactivity of the strained double bond in the bicyclopropylidene moiety of these molecules (Scheme 55) [145]. 

The rhodium-catalyzed PK reaction has many unique features as compared to the original cobalt-mediated version. For example, most of the rhodium-catalyzed reactions could be carried out under only 1 atm CO. Initially, these reactions were expected to proceed more effectively under higher CO pressures. However, experimental results demonstrated that the reaction was retarded by elevated CO pressure (>1 atm.), while the reaction at a lower CO pressure (0.1 atm.) proved to be superior [13b]. For example, the reaction of la with [RhCl(CO)2]2 under a high pressure of CO (3 atm.) afforded 2a in 70% yield, but was not complete after 36 h. The analogous reaction under a mixed CO/Ar atmosphere (1 atm. CO/Ar=l 9) was complete within an hour to afford 2a in 90% yield. 

Uracil derivatives can also participate in cobalt-mediated [2-f2-f2] cycloaddition reactions with dialkynes under photochemical conditions, to give cobalt complexed dihydrobenzo[g]quinazoline derivatives 482 <1999CEJ3549>. 

A catalytic variation of the cobalt method is the vitamin BI2a-mediated reaction to provide C-glycosides [24], The intermediate in this chain mechanism is the sugar cobalamine 45 formed by reaction of the precursor 43 with vitamin B 2a 44 (the brackets in Scheme 10 represent the corrin system) [25]. 

Efficient access to 23 finally allowed the examination of the pivotal cobalt-mediated [2 + 2 + 2]cycloaddition. Initial experiments employed bis(trimethylsilyl)acetylene (BTMSA) as a cocylization partner (Scheme 15). This alkyne had been used previously with great success, because it does not autocyclize and is relatively volatile and, hence, can be used as a solvent. However, while successful, the reaction generated a significant... 

A new and readily available catalytic system has been developed to open the cyclopropane ring in 4 + 2-1- 2-homo-Diels-Alder cycloadducts formed by reaction of norbornadienes and buta-1,3-diene.47 The cobalt-mediated homo-Diels-Alder reaction followed by this PtCB-promolcd isomerization is a key step in the efficient route to bicyclo[5.3.0]decanes. 

An aluminium-promoted, cobalt-mediated O C rearrangement reaction of cyclic enol ethers has been reported to give functionalized cyclohexanones with good diastereocontrol (Scheme 81).123 The product stereochemistry has been shown to be ( ) dependent on the 7Z-stereochemistry of the starting enol ether. 

The essence of the cascade synthesis is depicted in Scheme 2.1. Two procedures, alkylation and reduction, comprised the [a — b — a — b — ] sequence. Thus, treatment of a diamine with acrylonitrile afforded tetranitrile 3. Cobalt-mediated nitrile reduction gave tetraamine 4. Further amine alkylation provided the second generation octanitrile 5. The nonskid-chain-like [2] synthesis is shown in Scheme 2.2. Construction of polycyclic 6 was accomplished by repetitive alkylation, reduction, acylation, and reduction (a — b c— d—>a- b— ...) sequences. Again, repetitive and multiple reaction sequences were employed for the generation of new molecular assemblies. Most notable about these syntheses is that for the first time, generational molecules were prepared and characterized at each stage of the construction process. 

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