Carbonylation of esters

The Tebbe reagent is quite useful in that it reacts with the carbonyl of esters to give vinyl ethers. Pine showed that 683 reacted with methyl benzoate to give an 81% yield of 1-methoxy-l-phenylethene. O Similar reaction of lactone 686 with 683 gave the exo-methylene vinyl ether 687 in Holmes synthesis of (+)-laurencin.571 The Tebbe reagent also reacts with conjugated esters via 1,2-addition to give the vinyl ether. ... 

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. 

Kice and co-workers have investigated systematically the electrophilic behavior of sulfur atoms in the various oxidation states. As anticipated, it is found that the hardness increases in the order sulfenyl < sulfinyl < sulfonyl (165, 166). The sulfenyl S is a typical soft acceptor, whereas the sulfinyl group is medium soft and approximates the tetrahedral carbon. The sulfonyl S is as hard as the carbonyl of esters (167). The opposite characteristics of sulfinyl and sulfonyl S are qualitatively predicted, as the sulfinyl S has a lone-pair of electrons, whereas the sulfonyl counterpart does not, and there is a significantly higher positive charge residing on the sulfonyl sulfur than the sulfinyl S atom. 

The mechanism of the reaction is as shown in equations (13.139) and (13.140). This reaction is also catalyzed by compounds of other metals of groups 8 and 9 such as ruthenium and iridium. Higher alcohols EtOH, Pr"OH, Pr OH also undergo carbonylation to give corresponding carboxylic acids.However, the rate of the reaction is lower. It is assumed that in this case, the oxidative addition of alkyl iodide to the rhodium(I) complex proceeds according to a radical mechanism. Hydrocarboalkoxylation, carbonylation of esters, reductive carbonylation of... 

Problem 5.18. From the data in Table 5.17, it is clear that protons a to the carbonyl of esters are less acidic than those a to the carbonyl of ketones. How might you account for this observation ... 

From these studies of the mode of action of carboxypeptidase A, the following two points can be extracted (a) the Zn(II) ion presumably complexes the carbonyl of ester and amide substrates, and (b) Glu-270 is also implicated as a participant, and both general-base and nucleophilic mechanisms have been proposed. There is also strong evidnece that the mechanisms are different with esters and amides. However, another mechanistic possibility to be envisaged for carboxypeptidase A is to consider a nucleophilic attack of the substrate ester or amide bond by Zn(II) coordinated hydroxide ion. Such a possibility was scrutinized by T. H. Fife and V. L. Squillacote (223). In particular, they examined the hydrolysis of the carboxyl substituted ester, 8-quinolyl hydrogen glutarate in the presence of Zn(II) ion. 

The first step is the interaction of the basic catalyst with the ester to produce the carbanion (I) the carbanion so formed then attacks the carbonyl carbon of a second molecule of ester to produce the anion (II), which is converted to ethyl acetoacetate (II) by the ejection of an ethoxide ion. Finally (III) reacts with ethoxide ion to produce acetoacetic ester anion (IV). This and other anions are mesomeric thus (IV) may be written ... 

F.N. Tebbe (1978 [footnote 20]) and R.R. Schrock (1976) have shown that electrophilic titanium or tantalum ylides can alkylidenate the carbonyl group of esters. Vinyl ethers are obtained in high yields with Tebbe s reagent, p-chlorobis(ri -2,4-cyclopentadien-l-ylXdime-thylaluminum)- 4-methylenetitanium (S.H. Pine, 1980 A.G.M. Barrett, 1989). 

The first report of oxidative carbonylation is the reaction of alkenes with CO in benzene in the presence of PdCh to afford the /3-chloroacyl chloride 224[12,206]. The oxidative carbonylation of alkene in alcohol gives the q, f3-unsaturated ester 225 and /3-alkoxy ester 226 by monocarbonylation, and succinate 111 by dicarbonylation depending on the reaction conditions[207-209]. The scope of the reaction has been studied[210]. Succinate formation takes... 

Treatment of 7r-allylpalladium chloride with CO in EtOH affords ethyl 3-butenoate (321)[284]., 3, y-Unsaturated esters, obtained by the carbonylation of TT-allylpalladium complexes, are reactive compounds for 7r-allyl complex formation and undergo further facile transformation via 7r-allylpalladium complex formation. For example, ethyl 3-butenoate (321) is easily converted into 1-carboethoxy-TT-allylpalladium chloride (322) by the treatment with Na PdCL in ethanol. Then the repeated carbonylation of the complex 322 gives ethyl 2-... 

Pd(II) salts promote the carbonylation of organomercury compounds. Reaction of phenylmercury chloride and PdCh under CO pressure affords benzophenone (429)[387]. Both esters and ketones are obtained by the carbonylation of furylmercury(Il) chloride in alcohol[388]. Although the yields are not satisfactory, esters are obtained by the carbonylation of aryl- and alkylmercuryfll) chlorides[389,390]. One-pot catalytic carbonylation of thiophene, furan, and pyrrole (430) takes place at the 2-position via mercuration and transmetallation by the use of PdCb, Hg(N03), and CuCl2[391]. 

Organotelluriumfll and IV) compounds undergo transmetallation with Pd(II)[414], The carbonylation of the alkenylphenyltellurium(II) 459 gives the a,/3-Unsaturated ester 460 and benzoate, 460 being the main product[415], Reductive coupling of diaryl, dialkyl, and aryl alkyltellurides 461 to give 462 proceeds by treatment with Pd(OAc)2[416,417],... 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

Carbonylation of the complex 548 proceeds in ethanol gives ethyl 3-chloro-3-butenoate (554), The lactone 555 and the two esters 556 and 557 are obtained by carbonylation of the dimeric complex 549. The oxidative carbonylation of allene in ethanol with PdCl2 gives ethyl itacoante (558), although the yield is low[498]. 

The catalytic oxidative carbonylation of allene with PdCb and CuCh in MeOH affords methyl a-methoxymethacrylate (559)[499]. The intramolecular oxidative aminocarbonylation of the 6-aminoallene 560 affords the unsaturated J-amino ester 561. The reaction has been applied to the enantioselective synthesis of pumiliotoxin (562)[500]. A similar intramolecular oxycarbonyla-tion of 6-hydroxyallenes affords 2-(2-tetrahydrofuranyl)acrylates[501]. 

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]. 

In the total synthesis of zearaienone (451), the ester 450 was prepared by the carbonylation of the crowded aryl iodide 448. The alkyl iodide moiety in the alcohol molecule 449 is not attacked[306]. Methyl trifluoromethacrylate (453) was prepared by the carbonylation of 3,3,3-trifluoro-2-bromopropylcne (452), The carbonylation in the presence of alkylurea affords 454. which is converted into the trifluoromethyluracil 455[307],... 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Triflates of phenols are carbonylated to form aromatic esters by using PhjP[328]. The reaction is 500 times faster if dppp is used[329]. This reaction is a good preparative method for benzoates from phenols and naphthoates (473) from naphthols. Carbonylation of the bis-triflate of axially chiral 1,1 -binaphthyl-2,2 -diol (474) using dppp was claimed to give the monocarboxy-late 475(330]. However, the optically pure dicarboxylate 476 is obtained under similar conditions[331]. The use of 4.4 equiv. of a hindered amine (ethyldiisopropylamine) is crucial for the dicarbonylation. The use of more or less than 4.4 equiv. of the amine gives the monoester 475. 

Carbonylation of enol triflates derived from ketones and aldehydes affords Q,/)-unsaturated esters[332]. Steroidal esters are produced via their aryl and enol triflates[328]. The enol triflate in 477 is more reactive than the aryl tritlate and the carbonylation proceeds stepwise. First, carbonylation of the enol triflate affords the amide 478 and then the ester 479 is obtained in DMSO using dppp[333]. 

Heteroaromatic esters such as 493 and amides are produced by the carbo-nylation of heterocyclic bromides[347,348]. Even dichloropyrazine (494) and chloropyridine are carbonylated under somewhat severe conditions (120 C, 40 atm)[349]. The carbonylation of trifluoroacetimidoyl iodide (495) proceeds under mild conditions, and can be used for the synthesis of the trifluoromethyl-glycine derivatives 496 and 497(350]. 

The aryl- and heteroarylfluorosilanes 541 can be used for the preparation of the unsymmetrical ketones 542[400], Carbonylation of aryl triflate with the siloxycyclopropane 543 affords the 7-keto ester 545. In this reaction, transme-tallation of the siloxycyclopropane 543 with acylpalladium and ring opening generate Pd homoenolate as an intermediate 544 without undergoing elimination of/3-hydrogen[401],... 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Particularly alkyl halides which have a perfluoroalkyl group at the /3-position undergo smooth carbonylation. Probably the coordination of fluorine to form a five-membered chelate ring accelerates the reaction. Double carbonylation to give the a-keto amide 915 is possible in Et NH with the fluorine-bearing alkyl iodide 914[769,770]. The ester 917 is obtained by the carbonylation of the /3-perfluoroalkyl iodide 916 in ethanol. 

Under CO pressure in alcohol, the reaction of alkenes and CCI4 proceeds to give branched esters. No carbonylation of CCI4 itself to give triichloroacetate under similar conditions is observed. The ester formation is e.xplained by a free radical mechanism. The carbonylation of l-octene and CCI4 in ethanol affords ethyl 2-(2,2,2-trichloroethyl)decanoate (924) as a main product and the simple addition product 925(774]. ... 

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