Intramolecular cobalt-catalyzed

However, in another contribution, Chung and coworkers realized the one-pot synthesis of [ S.5.5.6] fenestranes 42 via intramolecular cobalt-catalyzed tandem Pauson-Khand/Diels-Alder reactions of dienediynes 41 [44] (Scheme 21). 

Chang and co-workers developed an intramolecular cobalt-catalyzed cyclotrimerization of both the symmetric and the asymmetric nitrile-diyne... 

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. ... 

To summarize this section, to date 19 phenylenes have yielded to synthesis. They can be divided broadly into 5 families ( of examples) linear (3), angular/ helical (7), zigzag (2), bent (3) and branched (4). Their topologies have been accessed through 26 different routes, 15 of which involved in the crucial step an all-intramolecular cobalt-catalyzed cyclization, 9 used intermolecular variants and 2 a combination of the two strategies. 

Meissner, A. and Groth, U. (2010) Intramolecular cobalt-catalyzed [2-I-2-I-2] cycloaddition of O-protected diyne-cyanohydrins. Synlett, (7), 1051-1054. 

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],... 

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. 

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... 

Although a cobalt-catalyzed intermolecular reductive aldol reaction (generation of cobalt enolates by hydrometal-lation of acrylic acid derivatives and subsequent reactions with carbonyl compounds) was first described in 1989, low diastereoselectivity has been problematic.3 6 However, the intramolecular version of this process was found to show high diastereoselectivity (Equation (37)).377,377a 378 A Co(i)-Co(m) catalytic cycle is suggested on the basis of deuterium-labeling studies and the chemistry of Co(ll) complexes (Scheme 81). Cobalt(m) hydride 182, which is... 

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 reaction can be carried out intramolecularly to produce, in one step, three new rings in moderate yield (Equation (36)).149 It is noteworthy that up to six stereogenic centers could be formed. Additionally, cobalt-catalyzed [4 + 2 + 2]-cycloadditions of bicyclo[2.2.2]octadienes have been reported (Equations (37) and (38)).150... 

Morken and co-workers have reported the highly enantioselective version of this reaction, albeit with low efficacy in the aldol-type coupling [8d, e]. Unfortunately, we obtain low enantioselectivity ee 2-4%) using chiral rhodium complexes under our reaction conditions. An intramolecular adaptation has led to new opportunities in cobalt-catalyzed carbocyclizations, wherein the use of PhSiHs was essential for smooth ring formation (Eq. 4) [9]. The identical products were also formed by a combination of [Rh(COD)2]OTf/(p-CE3Ph)3P and molecular hydrogen [10]. 

Fig. 80 (Porphyrin)cobalt-catalyzed intramolecular C-H amination 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. 

A major initial limitation of the benzocyclobutene approach to o-quinodimethanes was the lack of efficient, large-scale syntheses for many specifically substituted derivatives. Fortunately, recent developments have lemov much of this impediment. Q>nceptually, the synthesis of benzocyclobutenes from aromatic precursors can be envisaged in only a limited number of ways. These include [2 -i- 2] cycloadditions involving benzynes and alkenes, intramolecular cyclization on to a benzyne, cyclizations involving arene anions, and electrocyclic closure of o-quinodimethanes. Benzocyclobutene derivatives can also be prepared by aromatization of bicyclo[4.2.0]octanes. Detailed discussion of variations to these approaches can be found in the cited reviews. The cobalt catalyzed co-oligomerization of 1,5-hexadiynes with al-kynes, especially bis(trimethylsilyl)acetylene, has also been employed for the preparation of specifically substituted benzocyclobutenes. In the latter case the cyclobutenes are often not isolated but converted directly to o-quinodimethanes and subsequent products. ... 

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],... 

Tab. 3.28 Cobalt-catalyzed intramolecular Heck-type conversion...

Fujioka, T., Nakamura, T., Yorimitsu, H. and Oshima, K. (2002) Cobalt-catalyzed intramolecular Heck-type reaction of 6-halo-l-hexene derivatives. Org. Lett., 4, 2257-9. 

The all-carbon dienynes 28a-d and 30a-c were prepared and their intramolecular cycloadditions studied (Schemes 18 and 19). No reaction was observed upon treatment of 28a at 150 °C in the absence of the catalyst. However, under cobalt-catalyzed conditions, cycloadditions occur smoothly. 

The cobalt-catalyzed reaction is applicable to intramolecular cyclization of 6-halo-1-hexene derivatives (Table 2). In the intramolecular version, dppb, l,4-bis(diphenylphosphino)butane, is the best ligand, and a higher temperature is necessary. The same system also effects the conversion of aryl iodides having an olefinic moiety at a proper position into the cyclized product (eq33). 

Table 2 Cobalt-catalyzed intramolecular cyclization of 6-halo-1-hexene derivatives...

Cobalt-catalyzed cyclocotrimerization of alkynes and nitriles was pioneered by Wakatsuki, Bonneman, and co-workers [55], Highly selective intramolecular versions of this powerful pyridine-ring annulation were developed further using cobalt, rhodium, and nickel catalysts by Vollhardt, and others [53], These reactions include... 

A concise synthesis of the cytotoxic alkaloids dehydrotylophorine (127) and (+)-tylophorine (128) has been accomplished by a cascade consisting of a cobalt-catalyzed crossed [2 - - 2 - - 2] cyclotrimerization that is followed by an intramolecular ring annulation reaction (Scheme 7.27) [37],... 

Stard, Stary, and co-workers utilized the complete intramolecular [2-1-2+ 2] cycloaddition approach for the synthesis of heterohelicenes. The cobalt-catalyzed intramolecular [2- -2-f-2] cycloaddition of a pyridine-linked triyne followed by dehydrogenation with MnOa afforded an l-aza-[6]helicene in good yield (Scheme 10.8) [10], A 2-aza-[6]helicene could also be synthesized by this method (Scheme 10.8) [10],... 

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