Cyclization with Carbon Monoxide

Murai and coworkers showed a ruthenium-catalyzed cyclocarbonylation of yne-aldehydes in 1998 (Eq. (7.16)) [22]. In the presence of a catalytic amount of Ru3(CO)j2 the reaction of yne-aldehyde with CO (10 atm) in toluene at 160 °C gave a series of a, -unsaturated bicyclic y-butenoUdes in high yields. It is noteworthy that polyfunctional compounds could be formed in a single step by employing this method. 

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. 

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Sbderberg et al. have developed a sequence of Stille coupling followed by palladium (O)-catalyzed reductive N-heteroannulation for the synthesis of tetrahydrocarbazo-lones 238 (Scheme 57) [216, 217]. Palladium(0)-catalyzed coupling of 2-nitroar-ylstannanes 236 with 2-iodo-2-cyclohexenones 235 afforded the 2-(2-nitrophenyl)-2-cyclohexenones 237. Cyclization with carbon monoxide in the presence of catalytic amounts of bis(dibenzylideneacetone)palladium, l,3-bis(diphenylphos-phino)propane (dppp), and 1,10-phenanthroline led to the corresponding tetrahy-drocarbazolones 238 which can be transformed to the carbazoles 32 by Wolff-Kishner reduction and subsequent aromatization. This approach has been applied to the formal synthesis of murrayaquinone A [216]. 

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. 

Ureas of anilines 84 can also be lithiated" The products are generally very hard to cleave, but quenching the intermediate organolithiums 85 with carbon monoxide generates acyllithiums 86 which cyclize to give isatins 87 (Scheme 40)" . 

Cyclopentadienones.2 Cyclopentadienones are generally not useful synthons because of their ready dimerization. A new synthesis of more stable substituted cyclopentadienones involves cyclization of two substituted alkynes with carbon monoxide by the [2 + 2 + 21cycloadditions shown in equations (I) and (II). 

Indole synthesis.1 Indoles are formed by deoxygenation of o-nitrostyrenes with carbon monoxide catalyzed by Fe(CO)5 to give a nitrene, which undergoes intramolecular cyclization. Ru3(CO)12 and Rh6(CO)16 show comparable selectivity. Example ... 

When nonconjugated dienes react with carbon monoxide and water in the presence of dicobalt octacarbonyl, saturated and unsaturated cyclic ketones are produced (55, 77). This appears to be due to the formation of unsaturated acylcobalt carbonyls followed by cyclization, as discussed in Section II, B,3. 

Eq. 4.54 shows the reaction of n-heptanol (151) with Pb(OAc)4 under high-pressured carbon monoxide with an autoclave to generate the corresponding 8-lactone (152). This reaction proceeds through the formation of an oxygen-centered radical by the reaction of alcohol (151) with Pb(OAc)4,1,5-H shift, reaction with carbon monoxide to form an acyl radical, oxidation of the acyl radical with Pb(OAc)4, and finally, polar cyclization to provide 8-lactone [142-146]. This reaction can be used for primary and secondary alcohols, while (3-cleavage reaction of the formed alkoxyl radicals derived from tertiary alcohols occurs. 

As described in Section II.A, the tandem sequence reaction of organolithium compounds with carbon monoxide followed by reaction with suitable electrophiles provides an useful tool for the preparation of diphenyldialkyl carbinols, and the reaction could be easily extended to produce substituted cyclic ethers in a one-pot synthesis. Thus, by carrying out the carbonylation of phenyllithium in the presence of conveniently substituted chloroalkyl bromides, Br(CH2)3+ Cl, at -78 °C, the oxo-lithiated intermediates 243 are obtained and cyclized to 244 by warming up the reaction mixture (Scheme 74)21. 

The reaction of aromatic orf/zo-substituted imidoyllithiums 56 with carbon monoxide and methyl iodide afforded li/-isoindole derivatives 61 in moderate yields (Scheme 16)77. In this process the formation of an acyllithium 57 was proposed to occur which, after formation of intermediate 58, cyclized to give the compound 59. The rearrangement of the alkyl group giving the aromatic product 60, followed by quenching with methyl iodide at — 78 °C, gave indolines 61. 

ALTAM A process for making caprolactam from butadiene and carbon monoxide. Developed by DSM in the late 1990s and subsequently improved by Shell Chemicals, which contributed catalyst know-how. In the first two steps of the process, butadiene undergoes two hydroformylations with carbon monoxide, followed by reductive animation with ammonia and then cyclization to caprolactam. First commercialization was expected in Taiwan. A joint venture with Chiyoda Corporation, to further develop and commercialize the process, was announced in 2002. 

Buchwald and his group have also synthesized y-butyrolactones successfully by a metallocene mediated cyclization of enones (and ynones) with carbon monoxide in a formal [2-r2-rl]-ad-dition, and have thus achieved the first hetero-Pauson-Khand reaction [31]. The reactions can be conducted in high yields with either stoichio-metrical or catalytical amounts of [Cp2Ti(PMe,)2] as the example in Scheme 9 shows. 

A new oxidative cyclization of propargylic acetates to 1,3-dioxolanes has been achieved using a palladium(ll) catalyst with carbon monoxide in methanol (Equation 48) <2002TL6587, 2006T2545>. 

A variant of this process, studied by DuPont and DSM [32c], includes the hydrocarboxylation (hydroxycarbonylation) of butadiene with carbon monoxide and water this technology offers potential savings in raw material costs. The reaction primarily yields 3-pentenoic acid using a palladium/crotyl chloride catalyst system, with a selectivity of 92%. Further conversion of pentenoic acids by reaction with carbon monoxide and methanol and a palladium/ferrocene/phosphorous ligand catalyst has demonstrated a selectivity to dimethyl adipate of 85% the latter is finally hydrolyzed to AA. The main problem in this reaction is the propensity of pentenoic acid to undergo acid-catalyzed cyclization to y-valerolactone one way to circumvent the problem is to carry out the hydrocarboxylation of pentenoic acid using the y-valerolactone as the solvent. 

Several mechanisms are possible for these cyclizations. Formation of the dioxide (4) from the unknown 2,2 -dinitrosobiphenyl would parallel the dimerization observed with acyclic nitrosoarenes, and all the other cycliza-tion steps shown in Scheme 1 could be simple condensations, or involve radical anions, or radicals. Where deoxygenating reagents are used, there is also the possibility of cyclization via nitrene intermediates. It has been reported that low yields of benzo[c]cinnolines result from reduction of 2,2 -dinitrobiphenyls with carbon monoxide in the presence of iron penta-carbonyF or by heating in triethyl phosphite. In polarographic reduction studies, Ross et al - claimed to have demonstrated the sequence ... 

Nearly quantitative yields are obtained when 1,4-dienes containing a quaternary center at carbon-3 (R = alkyl, aryl, not H) are converted in the presence of rhodium catalysts 13 14. Here double-bond isomerization in the substrate to form conjugated dienes is suppressed. This hydrocarbonylative cyclization of 1,4-dienes with carbon monoxide gives cyclopentanone products with medium to high regio- and stereoselectivities14-17. Thus, the hydrocarbonylative cyclization of 2.3,3-trimethyl-1.4-pentadiene and similar substrates give predominantly the m-producls [turns cis 1 6). 

Aryl-, alkenyl- and alkynylpalladium species readily undergo carbonylation reactions because carbon monoxide as a loosely bonded ligand can reversibly insert into any palladium-carbon bond [110]. Thus, 2-allyl-l-iodocyclopentene (148), under palladium catalysis, reacts with carbon monoxide in two modes, depending on the excess of carbon monoxide and the catalyst cocktail (Scheme 3-39) [110a]. With a slight excess (1.1 atm of CO) in the presence of [Pd(PPh3)4] in tetrahydrofuran, 148 cyclized with one CO insertion to yield 3-methylenebicyclo[3.3.0]oct-l(5)-en-2-one (152), and under 40 atm of CO with [Pd(PPh ,)2Cl2] in benzene/acetonitrile/methanol, methyl 2- 3 -(2 -oxobicyclo[3.3.0]oct-1 (5 )-enyl) acetate 149 after two CO insertions (Scheme 3-39). 

C-labeled carbamoyl compounds can be prepared by using a selenium-mediated reaction with [ carbon monoxide. The urea formation works excellent in the case of cyclizations but in other cases satisfactorily only with primary amines (Kihlberg et al. 2002). Since selenium is practically insoluble in most solvents the use of primary alkyl amines or tetrabutylammonium fluoride is necessary for the formation of soluble and reactive complexes with selenium. Except for ring closures, rhodium-promoted carbonylations are probably more useful than the corresponding selenium reactions (Ohad et al. 2009). 

Since the reaction proceeds under an atmosphere of carbon monoxide in the usual cases, we can use a balloon that is filled with carbon monoxide and is connected to the top of the reaction vessel. If compounds have these functional groups and the hydroxyl and amino groups or organometallic complexes in a tether, lactams, lactones, and cyclized ketones are produced. Pd-catalyzed reactions can be classified into two types Pd(0)-catalyzed reactions and Pd(ll)-mediated or -catalyzed reactions. In each case, we can obtain the desired esters and amides. In the former reaction, a catalytic amount of palladium catalyst is required. In the latter reactions, a stoichiometric amount of palladium complex is required, but the reaction proceeds by a catalytic amount of Pd(ll) complex in the presence of oxidizing agents such as CuCl2 or benzoquinone. 

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