Reactions alkoxycarbonylation

Hydroxycarbonylation and alkoxycarbonylation of alkenes catalyzed by metal catalyst have been studied for the synthesis of acids, esters, and related derivatives. Palladium systems in particular have been popular and their use in hydroxycarbonylation and alkoxycarbonylation reactions has been reviewed.625,626 The catalysts were mainly designed for the carbonylation of alkenes in the presence of alcohols in order to prepare carboxylic esters, but they also work well for synthesizing carboxylic acids or anhydrides.137 627 They have also been used as catalysts in many other carbonyl-based processes that are of interest to industry. The hydroxycarbonylation of butadiene, the dicarboxylation of alkenes, the carbonylation of alkenes, the carbonylation of benzyl- and aryl-halide compounds, and oxidative carbonylations have been reviewed.6 8 The Pd-catalyzed hydroxycarbonylation of alkenes has attracted considerable interest in recent years as a way of obtaining carboxylic acids. In general, in acidic media, palladium salts in the presence of mono- or bidentate phosphines afford a mixture of linear and branched acids (see Scheme 9). 

The alkoxycarbonylation reaction is also feasible with 6-exo-nng closure for the preparation of stereodefined THP rings. Using this process, the integral THP moieties of frenolicin B,428 leucascandrolide A,429 and phorboxazole A (Equation (119))430 431 have been prepared. All of these reactions occur with 2,6-m-selectivity, a rationale for which has been advanced by an analysis of chair-like transition states.431... 

Although 2,5-dibromopyridine may be regiospecifically lithiated at C(5) [149], Pd-catalyzed couplings, including the Sonogashira, Negishi [150], and alkoxycarbonylation reactions [151] all preferentially occur at the C(2) position, as illustrated by the formation of 190. 

Abstract The use of Co building block in presence of water or an alcohol to functionalise alkenes by hydroxycarbonylation or alkoxycarbonylation reactions is reviewed in this chapter. The hydroxyl groups can be present in the substrate itself so cascade reactions can occur. Palladium precursors are largely involved in these reactions and this analysis of the literature focuses on the mechanisms involving Pd(0), Pd(H)(X)L2, PdX2 and an oxidant like CuCl systems. Introduction of chiral L or L2 ligands or even the presence of chiral carbon atoms in the substrate lead to asymmetric carbonylation reactions. 

The best enantioselectivity achieved so far was in intramolecular alkoxycarbonylation reactions. For example, using Pd(OAc)2 with a chiral diphosphine ligand on //-substituted allylic alcohols containing dialkyl substituents at the a-position gave good enantioselectivity [105,106]. More recent studies show that it is possible to carbonylate enantioselectively p,/-substituted allylic alcohols [107]. Thus, following the observations achieved with non-chiral Pd(0)(dppb) complexes that fraus-disubslituted lactones can be selectively produced from -substituted allylic alcohols [87], hindered chiral... 

Alkoxycarbonylation has been known for a long time, but the rates and selectivities of the new catalysts are outstanding. The mechanism of the alkoxycarbonylation reaction catalysed by palladium has been the topic of research for many years [55], Stepwise reactions had shown the feasibility of two mechanistic pathways, shown in Figure 12.20, but kinetic studies and in situ observations on catalytic systems were lacking. 

N-Acylation and 3-alkoxycarbonylation reactions may be achieved by conventional acylation procedures. A variety of 3-acyl derivatives 157 can be prepared most conveniently by the treatment of DPPOx 266 with carboxylic acids in the presence of a tertiary amine. tert-Butoxycarbonyl (Boc-Ox, 236) and benzyloxy carbonyl (Cbz-Ox, 267) (Cbz = benzyloxycarbonyl) compounds are of practical use for introduction of nitrogen protecting groups. ... 

Ukaji and co-workers employed bis(oxazoline) ligands in the asymmetric bis(alkoxycarbonylation) reaction of homoallylic alcohols. One example of this reaction, the conversion of homoallylic alcohol 200 to its carbonylation product 201, is illustrated in Figure 9.58. This reaction proceeded in 78% yield with an ee of 50%. 

Ryu and coworkers subsequently reported photochemically initiated radical alkoxycarbonylation reactions of alkyl iodides 177 using 5 mol% of Pd(PPh3)4 as the catalyst (Fig. 42) [210]. The reaction proceeds by light-stimulated reductive generation of an alkyl radical by the palladium(O) catalyst 179A. This radical has three options to react further. Direct addition to CO forms the acyl radical 177A. 

After James and Stille had shown the general possibility to link (intermolecular) alkoxypalladation and carbonylation processes 4], Semmelhack et al. were the first to achieve Pd-catalyzed intramolecular alkoxycarbonylation reactions and to apply them in the synthesis of specific target molecules [5]. In a typical reaction, the substrate is stirred at room temperature in methanol under an atmosphere of CO (I. I atm) in the presence of 5-10 mol% of PdCl2 and an excess (3 eq.) of CuClj. As the conversion of the simple model compound 4 to the products 5 and 6 implies, such reactions often proceed in good yields but not necessariliy with high diastereoselectivies (5 6 = 3 I). 

Through an intramolecular alkoxycarbonylation reaction catalyzed by palladium(II), 4-pen-tenc-l,3-diols give tetrahydrofuro[3,2-6]furan-2(3f/)-ones. The reaction is carried out by treating the unsaturated diol with palladium(ll) chloride, copper(ll) chloride and sodium acetate under a carbon monoxide atmosphere. The yields are good and five-membered rings are exclusively obtained with total regioselectivity, as shown by the cyclization of. sj -3-hydroxy-melhyl-5-hexene-l,4-diol (1), which affords only one product in 60% yield44. 

Moreover, starting from 2,9-dimethyl-10-undecene-4,6-diol (3), the alkoxycarbonylation reaction results in the corresponding tetrahydro-2//-pyran 4 in moderate yield and a cis/trans ratio of 89 1183. 

A useful extension of the alkoxycarbonylation reaction has been devised in order to obtain 3,4-dihydro-4-hydroxy-l//-2-benzopyran-3-acetic acid lactones from 5-alkene-l,4-diols. The intramolecular cyclization of 7, carried out with palladium(II) acetate and copper(II) chloride under a carbon monoxide atmosphere, affords the m-lactone 8 in 68% yield. The configuration is assigned on the basis of H-NMR double resonance methods86. 

Gebauer, M., Heinisch, G., Lotsch, G. Pyridazines. XXXIX. N-Substituted 1,2-dihydro-1,2-diazines formed in homolytic alkoxycarbonylation reactions of pyridazines. Tetrahedron 1988,44, 2449-2455. 

A comparitive study of a variety of lipases and lipase preparations in such alkoxycarbonylation reactions of amines has been presented by Sinisterra and coworkers181. 

The Minisci alkoxycarbonylation reaction can be used successfully (Equation (12)) for the preparation of mixed pyridazine-4,5-dicarboxylic acid esters in high yield using a two phase reaction mixture <87H(26)73l>. 

Another example of a carbonylation of chloropyridines is the synthesis of alkyl 3-chloropicolinates and dialkyl pyridine-2,3-dicarboxylates by Bessard and Roduit at Lonza Starting from 2,3-dichloro-5-(methoxymethyl)pyridine, both the mono- and the dicarbonylated pyridine derivatives can be obtained at low CO pressure (15 atm) with high selectivities and yields (Scheme 15). Utilizing PdCl2(PPh3)2 and dppb at 145 °C, 94% of methyl 3-chloropicolinate has been isolated, whereas palladium(II) acetate and dppf at 160 C leads to a double alkoxycarbonylation reaction. 

This alkoxycarbonylation reaction is also catalytic, if the alkylcobalt tetracarbonyl is formed from an epoxide and cobalt carbonyl anion in a hydroxylic solvent (9). A stoichiometric amount of base is not required in this reaction. The initial product, a derivative of the anion of 2-hydroxy-ethylcobalt tetracarbonyl, may undergo three reactions (a) react with more epoxide to give polymer, (b) undergo an internal hydride shift to form aldehyde or ketone, or (c) undergo protonation, carbon monoxide insertion, and alcoholoysis (or hydrolysis) to form ester (or acid). Varying amounts of... 

The alkoxycarbonylation reaction is also useful for the synthesis of spiroacetals (Scheme 24) [38] Thus, certain hydroxyenones react under the standard conditions in the presence of trimethyl orthoformate (TMOF) to afford the corresponding spiroacetals via hemiketal intermediates in high yield. It is also possible to prepare spiroacetals starting from dienones (Table 3). The stereochemistry of the products was not established however, this method is of potential value for the synthesis of bioactive compounds with spiro acetal substrucmre. 

Isolated mononuclear palladium(O) carbonyl complexes are relatively rare, although more examples have been identified in solution. This appears to be due to facile loss of GO from the palladium center. Those identified or isolated recently are based almost exclusively on monodentate or bidentate phosphine ligands, and result from studies of the alkoxycarbonylation reaction. The stability depends on the nature of the phosphine ligand, with bidentate chelating phosphines containing sterically demanding substitution affording the most stable complexes. 

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