Alkynes cobalt-catalyzed

A key intermediate, 163, which possesses all but one chiral center of (+ )-brefeldin, has been prepared by the enantiocontrolled cycloaddition of the chiral fi,/3-unsaturated ester 162 to 154[107], Synthesis of phyllocladane skeleton 165 has been carried out by the Pd-catalyzed cycloaddition of the unsaturated diester 164 and cobalt-catalyzed cycloaddition of alkynes as key reactions[108]. Intramolecular cycloaddition to the vinylsulfone in 166 proceeds smoothly to give a mixture of the trans and cis isomers in a ratio of 2.4 1[109], Diastereocontrolled cycloaddition of the hindered vinylsulfone 167 affords a single stereoisomeric adduct, 168, which is used for the synthesis of the spirocarbocyclic ring of ginkgolide[l 10],... 

Yong et al. developed a cobalt-catalyzed [2+2+2] cyclotrimerization of terminal alkynes in good yields in aqueous media (80/20 mixture of water and ethanol) at room temperature. A cyclopentadienyl cobalt complex bearing a pendant phosphine ligand was used as a catalyst (Eq. 4.59). The cyclotrimerization of internal alkynes resulted in lower yields and required an elevated temperature, most likely due to steric interactions. For example, cyclotrimerization of 2,5-dimethyl-3-hexyne gave hexaisopropylbenzene in 51% yield and the reaction of diphenylethyne resulted in a 47% yield of hexaphenylbenzene.112... 

The mechanism of [3 + 2] reductive cycloadditions clearly is more complex than other aldehyde/alkyne couplings since additional bonds are formed in the process. The catalytic reductive [3 + 2] cycloaddition process likely proceeds via the intermediacy of metallacycle 29, followed by enolate protonation to afford vinyl nickel species 30, alkenyl addition to the aldehyde to afford nickel alkoxide 31, and reduction of the Ni(II) alkoxide 31 back to the catalytically active Ni(0) species by Et3B (Scheme 23). In an intramolecular case, metallacycle 29 was isolated, fully characterized, and illustrated to undergo [3 + 2] reductive cycloaddition upon exposure to methanol [45]. Related pathways have recently been described involving cobalt-catalyzed reductive cyclo additions of enones and allenes [46], suggesting that this novel mechanism may be general for a variety of metals and substrate combinations. 

Recently, Oshima has reported a cobalt-catalyzed allylzincation of internal alkyne derivatives (Scheme 10). Optimization of the reaction leads to utilization of cobalt(ll) chloride in THF at room temperature. No traces of regio- and stereoisomers are obtained. The resulting alkenylzinc species 34 can be trapped with a large number of electrophiles in order to generate stereoselectively the tri- and tetrasubstituted alkenes 35-37. 

Malacria and co-workers76 were the first to report the transition metal-catalyzed intramolecular cycloisomerization of allenynes in 1996. The cobalt-mediated process was presumed to proceed via a 7r-allyl intermediate (111, Scheme 22) following C-H activation. Alkyne insertion and reductive elimination give cross-conjugated triene 112 cobalt-catalyzed olefin isomerization of the Alder-ene product is presumed to be the mechanism by which 113 is formed. While exploring the cobalt(i)-catalyzed synthesis of steroidal skeletons, Malacria and co-workers77 observed the formation of Alder-ene product 115 from cis-114 (Equation (74)) in contrast, trans-114 underwent [2 + 2 + 2]-cyclization under identical conditions to form 116 (Equation (75)). 

The cobalt-catalyzed pyridine synthesis is the only known one-step process for the selective preparation of the industrially significant 2-substituted-pyridine derivatives. Moreover, the method is applicable to a broad variety of substituted alkynes and nitriles, thereby giving access to a whole range of pyridine derivatives having 1,2,3 or 5 substituents in the ring. Selected examples follow and are compared to the prior state of the art. 

The cobalt catalyzed cocyclization of alkynes with heterofunctional substrates is not limited to nitriles. cpCo-core complexes are capable of co-oligomerizing alkynes with a number of C,C, C,N or C,0 double bonds in a Diels-Alder-type reaction. Chen, in our laboratories, has observed that these cycloadditions are best performed with the help of stabilizers such as ketones or acetic esters that are weakly coordinated to the cobalt and prevent the alkynes from being cyclotrimerized at the metal center... 

The oligomerization, cooligomerization and metathesis of small alkenes and alkynes and much of cobalt-catalyzed hydroformylation fall within the scope of the companion work Comprehensive Organometallic Chemistry and are not dealt with here. 

Vollhardf s group adopted the cobalt-catalyzed photochemical cyclotrimerization of alkynes for the rapid construction of a novel class of helicenes, helical [n]phe-... 

A carbon-carbon double bond of this intermediate then reacts with two alkyne units via a cobalt-catalyzed [2 + 2 + 2] process leading to a cobalt-1,3-cyclohexadiene complex which undergoes subsequent reductive elimination (Scheme 14). The regioselective outcome of this reaction was explained in terms of steric congestion. 

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. 

Silicon analogues 124 of the powerful musk odorant Versalide 123 were synthesized by a cobalt-catalyzed cyclization of l,2-bis(ethynyldi-methylsilyl)ethane (101) and alkynes (07OM1295) (Scheme 24). 

In contrast to carbocyclic alkyne cyclotrimerizations, the catalytic pyridine synthesis from alkynes and nitriles relies exclusively on cobalt catalysts with a few exceptions where rhodium [16] and iron complexes [17] could be applied. The cobalt-catalyzed pyridine synthesis can even be carried out in a one-potreac-tion generating the catalyst from C0CI2 6 H20/NaBH4 -1- nitrile/alkyne in situ [18]. 

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. 

Applying the versatility of the cobalt-catalyzed pyridine formation (eq. (2)), Vollhardt [45] has varied the basic reaction extensively. Using rather sophisticated alkyne and nitrile precursors with 77 -Cp-cobalt dicarbonyl as the catalyst, the preparation of a number of polyheterocyclic systems having physiological interest was brought about. Using eq. (14) a synthetic route to the isoquino[2,l-(7] [2,6]naphthyridine nucleus (eq. (16)) was developed [46]. 

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... 

Krafft, M. E., Hirosawa, C., Dalai, N., Ramsey, C., Stiegman, A. Cobalt-catalyzed homocoupling of terminal alkynes synthesis of 1,3-diynes. Tetrahedron Lett. 2001,42, 7733-7736. 

This behaviour correponds to the observation that other unsaturated hydrocarbons, e.g. alkynes, allenes or 1,3-butadienes, which readily undergo transition metal catalyzed cyclooligomerizations, do also incorporate CX multiple bonds in such cycloadditions only with difficulty in most cases 207 208). Besides the well known cobalt-catalyzed pyridin synthesis from alkynes and nitriles98 cocyclooligomerizations have been achieved with alkynes on one side and isocyanates 209), carbodiimides210) and carbondioxide 211) on the other side as well as with 1,3-butadienes and aldehydes 212), carbondioxide213 and 2-aza- or 2,3-diaza- 1,3-butadiene214. ... 

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],... 

Replacement of bis(l,2-diphenylphosphino)ethane by chiral phosphanes such as (— )-(25, 3 5)-bis(diphenylphosphino)butane or (- -)-(/ )- ,2-bis(diphenylphosphino)propane allows a highly enantioselective cobalt-catalyzed homo-Diels-Alder reaction (maximum 91% ee) between norbornadiene and monosubstituted alkynes. Similarly, the reaction of norbornadiene with phenylacetylene in the presence of catalytic amounts of tris(acetylacetonato)cobalt and (-l-)-bicyclo[2.2.1]hept-5-ene-2,3-diylbis(diphenylphosphane) leads quantitatively to the homo-Diels-Alder adduct with an ee of 98.4%. ... 

Cobalt-catalyzed synthesis from alkynes and nitriles 85AG264 86MI13 ... 

Nevertheless, nitrile functionalized ILs have been used for cobalt-catalyzed cyclotrimerization reactions of monosubstituted aromatic alkynes also in this case, the nitrile functionality was able to stabilize the transient cobalt(i) catalytic species, ensuring good conversions. ... 

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