Cyclocarbonylations catalytic

Carbonylation of C M bonds with transition metal catalysts has received significantly less attention than the corresponding insertion chemistry of C—X bonds [6]. With Pd(II) as the catalyst, transmetallation initiates the cyclocarbonylation catalytic cycle (Scheme 2.9). An oxidant is typically required to regenerate Pd(II) from Pd(0) following reductive elimination. 

Chiral lactones were also obtained by cyclocarbonylation of chiral acetylenic alcohols with Pd and thiourea (H2NCSNH2) (Scheme 32). No loss in chirality was observed, but large amounts of Pd and thiourea were used (10 mol %) since the catalyst deactivates by forming metal particles. The catalytic precursor (Pdl2 > PdCl2) and the ratio of thiourea to Pd were very important, thiourea being necessary for this reaction. The active species was supposed to be [Pd(thiourea)3l]I, which forms in situ from [Pd(thiourea)4]l2 and [Pd(thiourea)2]l2. It had to be a partially dissociated species since [Pd(thiourea)4](Bp4)2 was inactive [121]. 

Chiral lactones were also formed by cyclocarbonylation [ 122] with chiral catalysts, such as Pd-poly-L-leucine catalytic system. For example, but-2-en-l-ol led to the corresponding cychc chiral lactone in the presence of Pd catalysts with chiral ligands (Scheme 33). About 10 mol% of Pd(II) chloride... 

Hidai and co-workers found that 3-vinylindole 326 undergoes cyclocarbonylation to afford 1-acetoxycarbazole 327 [425]. The reaction of indole with allene and CO in the presence of catalytic Pd(0) leads to Af-acylation (328) in good yield [426], An analogous reaction with 5-hydroxyindole affords N- and O-acylation products (47% yield). 

Substituted propargylic alcohols were found to undergo direct carbonylation to the corresponding butenolides in 67-98% yield (Eq. 9.120) [86]. This reaction requires a catalytic amount of Pd2(dba)3-CHC13 (4%) and l,4-bis(diphenylphosphi-no)butane (8%) in CH2C12 under an atmosphere of CO (600 psi) and H2 (200 psi) at 95 °C for 36 h. The cyclocarbonylation reaction is believed to proceed via an allenyl-palladium intermediate, which is formed by initial insertion of Pd(0) into the C-O bond of the alkynol followed by rearrangement (Scheme 9.25). 

In order to obtain lactones from natural alkenols, we investigated the cyclocarbonylation of monoterpenic alcohols. The catalytic precursor is [PdCl2L2] in the presence of a slight excess of tin chloride and phosphine ligands. Dihydromyrcenol, a representative acyclic terpene containing a termi-... 

All these reactions are examples of oxidative cyclocarbonylation-alkoxy-carbonylation. However, the Pdh/KI catalytic system turned out to be a very efficient catalyst also for promoting cyclization-alkoxycarbonylation processes. In fact, optimal conditions were found for selectively converting 4-yn-l-ols into tetrahydrofuran derivatives (Eq. 41) [107] through 5-exo-dig cyclization followed by alkoxycarbonylation (Scheme 19, path a). This kind of process was not possible for the propynyl, 3-yn-l-ol, and 2-ethynylaniline substrates, seen before, for stereoelectronic reasons [302], With the latter substrates, the endo cyclization mode (Scheme 19, path b), although in principle stereo electronically allowed, was not observed. 

Cyclocarbonylation of o-iodophenols 503 with isocyanates or carbodiimides and carbon monoxide in the presence of a catalytic amount of a palladium catalyst (tris(dibenzylideneacetone)dipalladium(O) Pd2(DBA)3) and l,4-bis(di-phenylphosphino)butane (dppb) resulted in formation of l,3-benzoxazine-2,4-diones 504 or 2-imino-l,3-benzoxazin-4-ones 505 (Scheme 94). The product yields were dependent on the nature of the substrate, the catalyst, the solvent, the base, and the phosphine ligand. The reactions of o-iodophenols with unsymmetrical carbodiimides bearing an alkyl and an aryl substituent afforded 2-alkylimino-3-aryl-l,3-benzoxazin-4-ones 505 in a completely regioselective manner <1999JOC9194>. On the palladium-catalyzed cyclocarbonylation of o-iodoanilines with acyl chlorides and carbon monoxide, 2-substituted-4f/-3,l-benzoxazin-4-ones were obtained <19990L1619>. 

The catalytic cyclocarbonylations of diynes proceed efficiently to afford fused cyclohexadienes via trapping of the ruthenacyclopentadiene intermediate by an alkene component <2000JA4310>. Thus, the ruthenium-catalyzed cyclo-co-trimerization of 1,6-heptadiyne derivatives possessing a heteroatom at the 4-position affords heterotricycles in good yields (Equation 110). 

A catalytic asymmetric cyclocarbonylation of 2-(prop-l-en-2-yl)phenolprovides a route to (6)-4-methyldihydrocou-marin in excellent yield and with high enantioselectivity (Equation 417) <2004JOG5011>. 

Related cyclocarbonylations of enones or enals leading to y-butyrolactones were achieved using stoichiometric and catalytic amounts of titanocene and its... 

Recently, Buchwald and co-workers devised an outstanding procedure for the direct, titanocene-catalyzed cyclocarbonylation of enynes [19]. This catalytic method has a number of advantages it occurs at low CO pressure, tolerates a variety of functional groups including disubsti-tuted alkenes, and gives the cyclopentenones in high yields (>85 %). This industrially attractive process was later modified to proceed enan-tioselectively. With 5-20% of [(S,5)-(EBTHI)... 

The reaction was successfully extended to the hydroformylation of propargyl-type alcohols [154] and propargylamine [155], the silylative cyclocarbonylation of alkynes [156], silylcarbocyclization of alkenynes and diynes [157-160], and other transformations of C=C bonds in the presence of HSiRa and CO (e. g., [161]). A generalized catalytic cycle for the silylformylation of 1-alkynes catalyzed by rhodium-cobalt clusters is illustrated in Scheme 6. 

Rhodium carbonyl, Rh4(CO)I2, catalyzes the cyclocarbonylation of acetylenes with benzene to give indenones. For example 2,3-diphenyl -indenone is obtained from diphenyl acetylene and benzene in 10% yield, corresponding to a catalytic turnover of 11 (220°C, 25 bar, 7 hr)... 

Another important development in the area of catalytic Pauson-Khand type cy-clizations has been the discovery of other transition metal carbonyl complexes which are capable of effecting the catalytic synthesis of cyclopentenones. Two recent reports from Murai and Mitsudo detailed a Ru3(CO)i2-catalyzed enyne cyclocarbonylation, Eqs. (10) and (11) [34,35]. While this protocol allowed for the cyclization of a variety of l,6-enynes,the cyclizations of terminal alkynes as well as 1,7-enynes were problematic. The feasibility of using Cp2Ti(CO)2 as a catalyst for the intramolecular Pauson-Khand type cyclization of a variety of 1,6-and 1,7-enynes (vide infra) has also been demonstrated [36]. Based on the wide array of transition metals that are capable of effecting stoichiometric Pauson-Khand type cyclizations (vide supra), the development of more catalytic systems is to be expected this should greatly facilitate the search for catalytic asymmetric variants. 

In the course of studying the stoichiometric, carbonylative synthesis of y-buty-rolactones from enones and a titanocene complex [37], it was observed that certain aryl enones could be cyclocarbonylated in a catalytic manner, Eq. (12) [38]. This success in effecting a titanocene-catalyzed cyclocarbonylation led to an examination of the analogous reaction with enyne substrates. Indeed, it was found that under similar conditions, a titanocene-catalyzed Pauson-Khand type cyclization was possible, Eq. (13) [36]. 

This reaction profile, also called carbonylation, governs the reactivity of Pd-carbonyl complexes. Anionic M[Pd(CO)l3], for instance, catalyzes the reductive carbonylation of esters.f On the other hand, Pd(CO)(PPh3)3 was reported to catalyze the carboxymethy-lation of organic halides and the cyclocarbonylation of cinnamyl halides.f " However, the Pd-CO complexes are most often generated in situ from preformed alkyl -palladium complexes and CO under stoichiometric or catalytic conditions, for example, in the copolymerization of alkenes and CO. Decarbonylation reactions also involve the intermediacy of Pd-CO complexes. In this case, migratory deinsertion (Sect, n.3.1), that is, the microscopic reversal of the migratory insertion, takes place. 

The group of Murai [14] could demonstrate that ruthenium-catalyzed cyclocar-bonylation of yne-imines resulted in formation of lactams (Scheme 1.4a). Catalytic amounts of Ru3(CO)j2 promote this cyclocarbonylation of 1,6- and 1,7-yne-imines, giving bicychc a,fi-unsaturated lactams. Similar to the Pauson-Khand reaction, the... 

Since Watanabe s synthesis of 4(3H)-quinazolinones in 1993 via transition-metal catalyzed reductive N-heterocychzation [ 181 ], several catalytic methods for quinazoline synthesis have been developed [182-186]. For example, palladium-catalyzed cyclocarbonylations of halides with appropriate reactants provided regioselective synthesis of 4(3H)-quinazolinone derivatives [182] and indoloquinazolines [184]. Also selenium-catalyzed reductive N-heterocyclization to quinazolinones has been developed by Sonoda et al. [183]. Copper-catalyzed heteroannulation with alkynes has been developed as highly region- and stereoselective route to 2-(2-arylvinyl)-l,2,3,4-tetrahydroquinazolin-4-ones 64 by Kimdu et al. [ 185] (Scheme 12). Recently, condensation of anthranylamide with various aldehydes to 4-quinazotinones has been found to give excellent yields in the presence of cupric chloride [186]. 

Pd-catalyzed endo-trig cyclocarbonylation of 2-en-l-oIs, bearing a terminal double bond and a secondary or tertiary alcoholic group, has also been carried out under neutral conditions, using Pd(dba)2/dppb as the catalytic system in DME at T = 190 °C and under... 

Cyclocarbonylation of unsaturated substrates incorporating a nucleophilic function (—YH) in a suitable position can also be effected in the presence of external nucleophiles (ZH) such as alcohols. These reactions usually result in oxidative dicarbonylation of the unsaturated bond and are promoted by Pd(ll) species. As ensuing dicarbonylation Pd(ll) is reduced to Pd(0), the presence of an oxidant is needed in order to make the process catalytic, as exemplified in Scheme 18 in the case of triple bond. 

Pd(II)-catalyzed cyclocarbonylation-alkoxycarbonylation of external 3-yn-l-ols to give (Z)-3-[(methoxycarbonyl)methylene]tetrahydrofuran-2-ones was achieved in excellent yields and catalytic efficiencies by using a copper-free catalyst based on... 

BMIPFfiOr BMINTf2 ILs were successfully employed for the palladium-catalyzed cyclocarbonylation of 2-allylphenols or anilines (Scheme 6.11) [93]. High yields of lactones or lactams are obtained with good selectivities. Moreover, the recovered IL catalytic solution can be reused without any significant changes in activity and selectivity. 

Many different substrates can undergo oxidative carbonylations, such as unsaturated and saturated hydrocarbons, aromatic and heteroaromatic derivatives, alcohols, phenols, and amines, giving a number of carbonyl compounds in a regio- and stereocontrolled fashion and with high degree of chemoselectivity. Oxidative car-bonylation reactions have been recently and carefully reviewed [10-13]. In this section a general overview of the most recent developments in oxidative carbonylations mediated by catalytic palladium(II) compounds and directed toward the synthesis of heterocyclic compounds is presented. As already reported in the introduction, the cyclocarbonylation reactions ending with the synthesis of simple lactones and lactams are reported in the chapter that discusses the carbonylation of alcohols and amines and are recently been reviewed [7,9,79]. 

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. 

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