Carbonylation double

The alkylurea 576 and oxamide 577 are formed by oxidative carbonylation of amines under CO pressure using Pd/C as a catalyst[518]. The urea formation proceeds under atmospheric pressure using PdCh and CuCl2[519]. The mono-and double carbonylations of / -aminoethanol (578 and 579) afford the cyclic carbamate (oxazolidinones) 580 and oxamide (morpholinediones) 581 [520,521]. 

The o-keto ester 513 is formed from a bulky secondary alcohol using tricy-clohexylphosphine or triarylphosphine, but the selectivity is low[367-369]. Alkenyl bromides are less reactive than aryl halides for double carbonyla-tion[367], a-Keto amides are obtained from aryl and alkenyl bromides, but a-keto esters are not obtained by their carbonylation in alcohol[370]. A mechanism for the double carbonylation was proposed[371,372],... 

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. 

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

A number of double carbonylations have been reported. In these reactions, two molecules of CO are incorporated in the product, leading to a-keto acids or their... 

Stereocontrol in the formation of spiroketals has been achieved in the alkylation of 2-(benzenesulfonyl)pyrans with allylsilanes <96JOC7860> and using a double carbonyl cycUsation strategy <96SL1065>. Spirocyclisation of protected dihydroxydiketones yields cis- and trans- l,7,9-trioxadispiro[5.1.5.3]hexadecanes the latter isomer is the thermodynamically more stable <96TL5461>. 

Xia and co-workers synthesised a number of Pd-NHC complexes (33, 34, 36) for carbonylative Suzuki reactions (Fig. 9.6) [41], Various aryl iodides were carbonylatively coupled (P = 1 atm) with either phenylboronic acid or sodium tetraphenylborate. All the complexes were highly active, but 33 provided the best results with >76% selectivity for ketone in all the reactions. Xia followed this work with the double carbonylation of various aryl iodides with several secondary amines using the catalysts [CuX(Mes)] (37-X) and [Cu(IPr)X] (38-X) (X = I, Br, Cl) (3 MPa, 100°C, 10 h) (Scheme 9.7) [42],... 

Scheme 9.7 General scheme for double carbonylation of aryl iodides with secondary amines...

Pd-catalyzed double carbonylation reactions are rare due to the inefficiency of formation of bis-carbonylation products. Addition of bulky tricyclohexylphosphine to the normal carbonylation system greatly facilitated the formation of the double carbonylation product. Subjecting 4-iodopyridine 199 to such conditions afforded primarily 4-pyridylglyoxylic acid derivative 200, which was not easily attainable via classical synthetic methods [159]. The monoamide 201 was isolated as a minor by-product. 

Cross double carbonylation of amines and alcohols Oxamates can be prepared by double carbonylation of amines and alcohols in the presence of (CH,CN)2PdCl2 as catalyst with 02 and Cul as oxidant and co-catalyst. This reaction is particularly efficient when applied to (3-amino alcohols. 

In an analogous approach explored by Dixneuf et al., a conjugated enynyl carbonate is converted into an oxolenone or a bicyclic lactone in significant yields via double carbonylation in the presence of methanol (Scheme 22) [128]. When a neighboring carbonyl group is present in the substrate, it can also participate in palladium-catalyzed cyclization-carbonylation. Indeed, 4-yn-l-ones lead to cyclic ketals that can be easily converted into 2-cyclopentenone carboxylates in an acidic medium (Scheme 22) [129]. 

Scheme 24 Double carbonylation of various butynols or propynols...

Under appropriate conditions, alcohols and amines can undergo an oxidative double carbonylation process, with formation of oxalate esters (Eq. 34), oxamate esters (Eq. 35) or oxamides (Eq. 36). These reactions are usually catalyzed by Pd(II) species and take place trough the intermediate formation of bis(alkoxycarbonyl)palladium, (alkoxycarbonyl)(carbamoyl)palladium or bis(carbamoyl)palladium complexes, as shown in Scheme 29 (NuH, Nu H = alcohol or amine) [227,231,267,293-300]. 

Not unexpectedly, alkylation of the double carbonylated complex proceeds via a base-catalysed interfacial enolization step, but it is significant that the initial double carbonylation step also involves an interfacial reaction, as it has been shown that no pyruvic acid derivatives are obtained at low stirring rates. Further evidence comes from observations of the cobalt-catalysed carbonylation of secondary benzyl halides [8], where the overall reaction is more complex than that indicated by Scheme 8.3. In addition to the expected formation of the phenylacetic and phenylpyruvic acids, the reaction with 1-bromo-l-phenylethane also produces 3-phenylpropionic acid, 2,3-diphenylbutane, ethylbenzene and styrene (Scheme 8.4). The absence of secondary carbonylation of the phenylpropionylcobalt tetracarbonyl complex is consistent with the less favourable enolization of the phenylpropionyl group, compared with the phenylacetyl group. 

For the preparation of a-ketoamides, palladium-catalyzed double carbonylation of aryl halides with carbon monoxide and secondary amines is also a useful reaction Kobayashi, T. Tanaka, M. J. Organomet. Chem. 1982, 233, C64 Ozawa, F. Soyama, H. Yamamoto, T. Yamamoto, A. Tetrahedron Lett. 1982, 23, 3383. 

Iterative two-directional chain elongation enables rapid construction of 1,3-polyols (Scheme 23). For example, the polyol substructure that appears in the oxopolyene macrolide (+)-roxaticin is available in nine steps from propane-1,3-diol upon three iterations of double carbonyl allylation [286]. Notably, high levels of catalyst-directed stereoselectivity are observed (For selected examples of catalyst directed diastereoselectivity, see [289-296]). Analogous 1,3-polyol syntheses via iterative homologation in one direction also are reported [297]. 

Mono- and double carbonylation of phenetyl bromide with cobalt-phosphine catalysts afforded benzylacetic (Baa) and benzylpymvic (Bpa) acids respectively [23] (Scheme 5.5). The highest yield of benzylpymvic acid (75 %) was obtained with [Co2(CO)8], while addition of the water soluble phosphines TPPMS or TPPTS decreased both the yield of carbonylated products and the selectivity to Bpa. 

Carbonylative coupling of iodobenzene with 2-methyl-3-butyn-2-ol under 65 bar carbon monoxide afforded phenylfuranones (double carbonylation) in reasonable yields (Scheme 6.32) [69]. The reaction is thought to proceed through the formation of a benzoylpalladium intermediate which either reacts with the alkynol or liberates benzoic acid hence the formation of considerable amounts of the latter. 

In a later work by Skoda-Foldes et al. [34], the same microreactor X-Cube system [32] was employed to perform the double carbonylation of iodobenzene... 

Ruy et al. have performed a similar reaction under microreactor conditions in a multiphase solvent system containing an ionic liquid as the catalyst carrier and reaction promoter [35]. Their system consisted of two T-shaped micromixers (i.d. 1,000 and 400 pm) and a capillary stainless steel tube as an RTU (1,000 pm i.d. and 18 m length, giving a 14.1 ml volume), equipped with pumps and control valves. Under the optimized conditions, Pd-catalysed carbonylation of aromatic iodides in the presence of a secondary amine provided only the double carbonylated product, ot-ketoamide, while the amide obtained by the single carbonylation was observed in high quantities only when the reaction was performed in batch (Scheme 13). 

Scheme 13 Pd-catalysed double carbonylation of aryl iodides [35]...

Balogh J, Kuik A, Urge L et al (2009) Double carbonylation of iodobenzene in a micro-fluidics-based high throughput flow reactor. J Mol Catal A Chem 302(l-2) 76-79... 

The factors that control the strictly alternating copolymer chain with no detectable errors (e. g., microstructures involving double insertion of ethene) have been the object of detailed studies since the discovery of the first Pd" catalysts for the alternating alkene/CO copolymerisation [11]. Sen was the first to demonstrate that double carbonylation is thermodynamically unfavorable and to suggest that the higher binding affinity of Pd" for CO relative to ethene inhibits multiple ethene insertions, even in the presence of very low concentrations of CO [12]. Therefore, once a palladium alkyl is formed, CO coordination ensures that the next monomer will be a CO molecule to generate the acyl complex. 

An efficient dinuclear Pd catalyst 299 was developed for the double carbonylation of iodobenzene with diethyla-mine/ which substantially improved the process yield (98%) and product selectivity of A, A -diethylphenyl-glyoxamide 301 (96%) (Equation (26)). 

The CoCl2-catalyzed double carbonylation of benzyl chloride was carried out in the presence of potassium pyridine-2-carboxylate and calcium hydroxide (3.75 equiv.) under 28 atm of CO to give phenylpyruvic acid in 70% yield (Equation (27)). ... 

The double carbonylation of iodobenzene with diethylamine catalyzed by Pd(OAc)2-PPh3 was carried out in l-butyl-3-methylimidazolium tetrafluoroborate 315 as reaction medium at 80 °C and 38 atm of CO to give phenyl-glyoxamide 314 as the predominant product (83%) accompanied by benzamide 313 (17%) (Equation (29)). The use of ionic liquids showed the same reactivity and product selectivity as those using diethylamine as solvent for this reaction, while separation of products and recycling of the catalyst was easier. ... 

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