Ruthenium carbonylative cyclization

Allyl methylcarbonate reacts with norbornene following a ruthenium-catalyzed carbonylative cyclization under carbon monoxide pressure to give cyclopentenone derivatives 12 (Scheme 4).32 Catalyst loading, amine and CO pressure have been optimized to give the cyclopentenone compound in 80% yield and a total control of the stereoselectivity (exo 100%). Aromatic or bidentate amines inhibit the reaction certainly by a too strong interaction with ruthenium. A plausible mechanism is proposed. Stereoselective CM-carboruthenation of norbornene with allyl-ruthenium complex 13 followed by carbon monoxide insertion generates an acylruthenium intermediate 15. Intramolecular carboruthenation and /3-hydride elimination of 16 afford the -olefin 17. Isomerization of the double bond under experimental conditions allows formation of the cyclopentenone derivative 12. 

Lee s group has also reported ruthenium-catalyzed carbonylative cyclization of 1,6-diynes. The noteworthy aspect of this cyclization is the unprecedented anti nucleophile attack on a 7i-alkyne complex bearing a ruthenium vinylidene functionality. A catalytic system based on [Ru(p-cymene)Cl2]2/P(4-F-C6H4)3/DMAP was active for the cyclization of 1,6-diyne 103 and benzoic acid in dioxane at 65 °Cto afford cydohexenylidene enol ester 104a in 74% yield after 24h [34]. Additional examples are shown in Scheme 6.35. 

Comparable lactones 19 can be synthesized from allenyl alcohols 18 by a ruthenium-catalyzed carbonylative cyclization [19] and an extension of this procedure to the synthesis of lactames 21 has also been reported [20]. 

Ruthenium complexes are also suitable catalysts for carbonylation reactions of a variety of substrates. Indeed, when a reaction leads to C-Ru or het-eroatom-Ru bond formation in the presence of carbon monoxide, CO insertion can take place at the coordinatively unsaturated ruthenium center, leading to linear ketones or lactones. Thus, ruthenium-catalyzed carbonylative cyclization was involved in the synthesis of cyclopentenones by reaction of allylic carbonates with alkenes in the presence of carbon monoxide [124] (Eq. 93). 

The reactions described in this section are not unique to ruthenium catalysis. These transformations can also be achieved using a palladium or a nickel catalyst. Since carbonylative cyclizations leading to cyclic carbonyl compounds are useful transformations in organic synthesis, these reactions are included in this section. 

Ruthenium-catalyzed carbonylations of allylic compounds [62] were described in Chapter 11. Here, ruthenium-catalyzed carbonylative cyclization of allylic carbonates with alkenes, not alkynes, which offers a new route to cyclopentenones is revealed [63]. Treatment of allyl methyl carbonate with 2-norbornene in the presence of 2.5 mol% [RuCl2(CO)3]2 and 10 mol% Et3N in THE at 120°C for 5 h under 3 atm of carbon monoxide gave the corresponding cyclopentenone, exo-4-methyltri-cyclo[5.2.1.0 ]dec-4-en-3-one, in 80% yield with high stereoselectivity exo 100%) (Eq. 5.37). 

Gold chloride forms an unstable complex with cyclo-octatetraene at low temperatures. This decomposes at — 20°C to l,2-dichlorocyclo-octa-3,5,7-triene, which gradually cyclizes to (562). In an attempt to form pentalene-metal complexes, cyclo-octatetraene was reduced to a mixture of trienes and bicyclo [4,2,0] octadiene, which was then treated with substituent ruthenium carbonyls, affording a variety of complexes, including (563). °... 

Oxygen nucleophiles Intramolecular oxa-Michael cyclization of a,/ -unsaturated carbonyl compounds (278) (e.g. thioesters, oxazolidinone imides, and pyrrole amides), catalysed by Brpnsted acids, such as camphorsulfonic acid (CSA), has been reported to afford 2,6-cis-substituted tetrahydropyrans (279) with good to excellent stereoselectivity (7 1 to >20 1 dr). The approach has been claimed to be superior to that mediated by bases and is complementary to the ruthenium-catalysed cyclization affording anal- 0 ogous products (149) discussed earlier. 

Quite recently, novel cyclization reactions involving CO to give carbocydic and heterocyclic compounds, which are characteristic for mthenium catalysts, have been developed. Ruthenium complexes provide new avenues for cydization reactions. In addition, CO is often used as a reducing agent, and reductive carbonylations of nitro compounds catalyzed by mthenium complexes are very attractive reactions that provide phosgene-free processes [3]. 

Ruthenium complexes catalyze the reaction of primary alcohols with o-phenylenediamine. The catalyst apparently has dual roles in promotion of cyclization and oxidation of the alcohol to aldehyde <91CL1275>. A novel palladium-catalyzed carbonylation of iodobenzene has been linked to base-induced coupling and cyclization with o-phenylenediamine to give 2-arylbenzimidazoles without having to use an arylcarboxylic acid (Scheme 152) <93JOC7016>. 

Several other examples of intramolecular ruthenium-, copper-, rhodium- and iron-catalyzed cyclizations via carbometalation with polyhalocarbons are known, with a range of stereoselectivities25 4 49. Similarly, palladium-catalyzed intramolecular ene-halogenocyclization" of unsaturated a-iodo carbonyl compounds, using Pd(dppe)2, has been applied to heterocyclic synthesis26 29. 

As already indicated, carbonyl compounds such as ketones, aldehydes, enones, and quinones possess the property to act as effective electron acceptors in the excited state for generating radical anions in the presence of electron-donating partners such as alkenes, aromatics, ruthenium complexes, amines, and alcohols. We will not consider the reactivity of enones and quinones, but we will focus our attention on the behavior of the radical anions formed from ketones and aldehydes. Four different processes can occur from these radical anions including coupling of two radical anions and/or coupling of the radical anion with the radical cation formed from the donor, abstraction of hydrogen from the reaction media to produce alcohols, cyclization, in the case of ce-unsaturated radical anions, and fragmentation when a C -X bond (X=0, C) is present (Scheme 18). 

Formation of ruthenium(m) complexes by attack at co-ordinated amines promises to be a useful synthetic method. Recent examples include the reactions of the [Ru(NH3)e] + ion with aldehydes (RCHO) to give the corresponding co-ordinated nitrile, [Ru(NH8)6(NCR)] + (R = Me or Ph, and the oxidant is unknown), or the reaction with glyoxal, MeCOCOMe, in the presence of hydroxide ion to give the ion (45). From kinetic studies of the latter reaction, a mechanism is proposed in which the [Ru(NH3)sNH2] ion attacks at one carbonyl centre of MeCOCOMe, followed by further deprotonation of the cis ammonia molecule, cyclization, and elimi-... 

On the other hand, when an enyne having a keto carbonyl group on the triple bond was reacted with Cp RuCl(cod) under ethylene gas, an unpredicted reaction took place giving cyclized compounds with a cyclopropane ring [103] [Eq. (43)]. Coordination of the carbonyl oxygen to the ruthenium center of the ruthenacyclo-pentene intermediate is responsible for the formation of a mthenium carbene able to react with ethylene to form a cyclopropane ring. 

In 2007, Trost and McClory reported the rhodium-catalyzed cycloaromatization of terminal alkynes bearing an amino or a hydroxy group (61 and 63) into the corresponding indoles and benzofurans (62 and 64) (Scheme 21.27) [36]. As described in the preceding section, McDonald et al. reported a similar transformation catalyzed by molybdenum carbonyl complex as a catalyst [10] (see Schemes 21.23 and 21.25). Use of rhodium catalyst provided some advantages in terms of the catalyst turnover and the selectivity. The combination of [RhCl(cod)]2 and a fluorinated triarylphosphine promoted the cyclization efficiently. Later, a ruthenium version of this cyclization was reported, as shown in Scheme 21.22 [31]. 

A ruthenium-based complex enabled catalytic carbonylative C-H cyclization of 2-arylphenols was achieved by using balloon pressure of CO and Oj (Eq. (7.17)) [23]. Under relatively mild reaction conditions, this methodology produced a variety of 6//-dibenzo [b,d] pyran-6-one derivatives in high yields with broad substrate scope. Competition experiment suggested that electron-rich substrates are more reactive. In addition, experiment with isotopically labeled substrate revealed that the C-H metalation step is reversible. 

Scheme 7.14 Proposed mechanism for ruthenium-catalyzed carbonylation and cyclization of aliphatic amides.

In 2013, Kondo and Inamoto reported the carbonylative C-H cyclization of 2-arylphenol with ruthenium complex as the catalyst and Af-heterocyclic carbene... 

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