Pd-catalyzed CO insertion

As with Heck olefination or Pd-catalyzed CO insertion, almost any organic bromide or iodide (without hydrogens attached to an. v/P-hybridizcd (3 carbon,... 

Finally, alkynyliodonium tosylates are subject to alkoxycarbonylation and formation of alkynoic esters, 66, via Pd-catalyzed CO insertion under very mild conditions [55] [Eq. (26)]. 

Yokozawa, T., and H. Shimura. 1999. Condensative chain polymerization. II. Preferential esterification of propagating end group in Pd-catalyzed CO-insertion polycondensation of 4-bromo-phenol derivatives. / Polym Sci A 37 (14) 2607-2618. 

The great majority of lactam syntheses by Pd-catalyzed CO insertion proceed by the well-established oxidative addition of a Pd(0) species to an alkenyl or aryl halide, followed by CO insertion and cyclization. The unsaturation can be endo to the newly formed ring or exo to it, as shown in Scheme 40 examples of both strategies abound. 

Alper and Hamel have reported an interesting case of Pd-catalyzed CO insertion reaction, involving ring expansion of aziridines to azetidinones (Scheme 47). It seems reasonable to assume that the reaction is initiated by oxidative addition of Pd(0) across the strained C—N bond, as shown below,... 

Palladium catalysts with simple monodentate phosphine ligands (e.g. PPh3) can catalyze the methoxycarbonylation of ethylene. However, the Lucite process employs a bulky diphosphine, 1,2-( Bu2PCH2)2CgH4, and is highly active and selective under quite mild conditions (10 bar/80°C). Two alternative catalytic cycles are possible, based either upon a palladium hydride or a palladium methoxide complex (Figure 9), and mechanistic and spectroscopic studies indicate that the hydride cycle is dominant. The alkene and CO insertion steps are the same as those in the Pd-catalyzed co-polymerisation of CO and alkenes to polyketones (Section 4.4). 

Arndtsen and co-workers have reported a palladium-catalyzed multicomponent coupling approach to miinchnones involving the reaction between an imine and an acid chloride followed by Pd coordination, CO insertion, and /3-hydride elimination to generate the product miinchnones in good yields (Scheme 19) <2003JA1474>. 

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

Similarly to alkenes. alkynes also insert. In the reaction of 775 carried out under a CO atmosphere in AcOH, sequential insertions of alkyne, CO. alkene. and CO take place in this order, yielding the keto ester 776[483]. However, the same reaction carried out in THF in the presence of LiCl affords the ketone 777, but not the keto ester[484]. The tricyclic terpenoid hirsutene (779) has been synthesized via the Pd-catalyzed metallo-ene carbonylation reaction of 778 with 85% diastereoselectivity as the key reaction[485], Kainic acid and allo-kainic acid (783) have been synthesized by the intramolecular insertion ol an alkene in 780, followed by carbonylation to give 781 and 782[486],... 

Palladium(O)- and Pd(II)-catalyzed carbonylation reactions have been the subject of several recent articles 32, 116, 119, 124, 173, 228, 232). In one case, the attending CO insertion into a Pd—C bond was shown to proceed with retention of configuration at carbon 131a, 218). 

Starting from 63, the carbonylation may proceed via coordination and insertion of CO into the vinyl-C-Pd bond to provide an a,P-unsaturated acyl complex. This complex reacts with (ArY) 2, and subsequently the C-Y bond is formed by reductive elimination to give 64 (Scheme 7-14). Because the compound 64 could be directly converted into the corresponding enal 65 by the Pd-catalyzed reduction with BujSnH, this sequence is synthetically equivalent to the regio- and stereoselective thioformy-lation and selenoformylation of alkynes (Eq. 7.49) [53, 54]. 

A very common combination in Pd-catalyzed domino reactions is the insertion of CO as the last step (this was discussed previously). However, there is also the possibility that CO is inserted as the first step after oxidative addition. This process, as well as the amidocarbonylation, the animation, the arylation of ketones, the isomerization of epoxides, and the reaction with isonitriles will be discussed in this section. 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

When Wacker-type reactions are performed under a CO atmosphere, the (3-H elimination pathway can be suppressed in favor of CO insertion and subsequent nucleophilic cleavage of the acyl metal species.399 This alkoxycarbonylation process has found widespread utility, particularly in the synthesis of five- and six-membered oxacyclic natural products. For example, the THF core of tetronomycin was prepared by the Pd-catalyzed alkoxycarbonylation of 4-alkenol derivatives (Equations (117) and (118)), where stereocontrol was achieved by utilizing either the directing ability of a free hydroxyl or the conformational bias imposed by a bulky silyl ether.420 Additional examples making... 

Larock and co-workers described the one-step Pd-catalyzed reaction of o-haloanilines with internal alkynes to give indoles [385, 386]. This excellent reaction, which is shown for the synthesis of indoles 303, involves oxidative addition of the aryl halide (usually iodide) to Pd(0),. vyw-insertion of the alkyne into the ArPd bond, nitrogen displacement of the Pd in the resulting vinyl-Pd intermediate, and final reductive elimination of Pd(0). 

In an alternative strategy functionalized phenols, such as iodophenol, were involved in palladium-catalyzed carbonylation of alkynes or allenes, producing coumarin or chromone derivatives (Scheme 23) [130-133]. After oxidative addition of the iodoarene to the Pd(0) catalyst the order of insertion of either CO or the unsaturated substrate mainly depends on the nature of the substrate. In fact, Alper et al. reported that CO insertion occurs prior to allene insertion leading to methylene- or vinyl-benzopyranone derivatives [130]. On the contrary, insertion of alkynes precedes insertion of CO, affording couma-rine derivatives, as reported by Larock et al. According to the authors, this unusual selectivity can be explained by the inability of the acyl palladium species to further react with the alkyne, hence the decarbonylation step occurs preferentially [131-133]. 

As is almost always true when when the substrate in a Pd-catalyzed reaction is C(sp2)-X, the first step is oxidative addition of Pd(0) to the C-I bond to give an arylpalladium(II) intermediate. (Although the Pd compound that is added to the reaction mixture is Pd(II), it is reduced in situ to Pd(0) by the mechanism outlined in the text.) Coordination of CO and insertion into the C-Pd bond gives an acylpalladium(II) intermediate. Deprotonation of the alcohol is followed by nucleophilic attack on the carbonyl C. Expulsion of Pd(0) gives the product and completes the catalytic cycle. 

Ethoxycarbonylation of 4,5-dibromo-2-methylpyridazin-3(2//)-one 202 under a high CO pressure in EtOH yielded diethyl l-methyl-6-oxo-l,6-dihydropyridazine-4,5-dicarboxylate 203 (Equation 46) <2005JHC427>. Surprisingly, aldehyde and ketone formation making use of Pd-catalyzed reactions involving CO insertion has not been studied yet. 

As Scheme 1 illustrates, the Pd-catalyzed process includes the formation of hemiamidal 1 in the same manner as that in the Co-catalyzed process. However, the unique feature in this process is that hemiamidal 1 is converted to a-bromoamide 2, which is the key intermediate in this process. Then, the oxidative addition of 2 to the Pd(0) species forms alkyl-Pd complex 3. Subsequent insertion of CO to the carbon-Pd bond of 3 gives the acyl-Pd complex 4, which leads to the formation of the A -acyl-a-amino acid 5 through reductive elimination and hydrolysis. 

The Pd-catalyzed reaction of 5-vinyl-l,3-oxazolidin-2-ones 260 at 65-70°C and 65 atm of CO in ethanol gave 5-lactams 263 in fairly good to high yields (Scheme 38).As Scheme 38 illustrates, this decarboxylative carbonylation reaction is likely to involve (i) the cleavage of the allylic C-O bond of 260 to form tr-allyl-Pd complex syn-2(A, (ii) isomerization to anti-2(A, (iii) decarboxylation forming 7r-allyl-Pd-amine complex 262, and (iv) CO insertion to 262 followed by aminolysis to yield 5-lactam 263. 

In 1996, Brookhart and co-workers developed a remarkable class of Pd complexes with sterically encumbered diimine ligands (Scheme 4, S4-1, S4-2, S4-4, and S4-5). These examples are capable of mediating the co-polymerization of ethylene with methyl acrylate (MA) to furnish highly branched PE with ester groups on the polymer chain ends by a chain-walking mechanism (Scheme 10). " This represents the first example of transition metal-catalyzed ethylene/MA co-polymerization via an insertion mechanism. The mechanism for co-polymerization is by 2,1-insertion of MA and subsequent chelate-ring expansion, followed by the insertion of ethylene units. The discovery of these diimine Pd catalysts has stimulated a resurgence of activity in the area of late transition metal-based molecular catalysis. Recently, the random incorporation of MA into linear PE by Pd-catalyzed insertion polymeriza-... 

Pd-catalyzed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pdf0) is dimerization with incorporation of nucleophiles. The bis-7r-allylpalladium complex 3 is believed to be an intermediate of 1.3,7-octatriene (7) and telomers 5 and 6[5,6], The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO IO] and C = N bonds of Schiff basesfl 1] and isocyanate[12] to form the six-mem bered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

Catalytic systems to afford linear esters selectively are scant.306,309 A report in 1995 disclosed that palladium complexes based on l,l -bis(diphenylphosphine)fer-rocene showed excellent regioselectivity for the formation of linear a,p-unsaturated esters.309 The results with phenylacetylene are remarkable because this compound is known to exhibit a distinct preference for the formation of the branched products on palladium-catalyzed carboxylations. Mechanistic studies indicate that the alkoxycarbonylation of alkynes proceeds via the protonation of a Pd(0)-alkyne species to give a Pd-vinyl complex, followed by CO insertion and alcoholysis.310... 

The first step of the Pd-catalyzed reaction of allyl acetate bearing allene moiety 284 is attack of the 7i-allyl group at the central carbon of the allene to form 285, (or insertion of one of the allene double bonds) which is the 7r-allylpalladium 286. Then domino insertions of double bond, CO, double bond, CO and double bond occur to form six C—C bonds, affording 287. Finally, the tetracyclic diketone 288 was obtained by -elimination in 22% total yield [127],... 

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