Carbonylation Alkoxycarbonylation

Compounds with methylene and methyne groups to which are attached two electronegative groups, such as carbonyl, alkoxycarbonyl, formyl, cyano, nitro, and sulfonyl groups, react with butadiene smoothly their acidic hydrogens are replaced with the 2,7-octadienyl group to give mono-and disubstituted compounds (59, 60). In addition, branched products are... 

Carbonylation, Alkoxycarbonylation and Aminocarbonylation of Double and Triple Bonds... 

Acyl-, 4-alkoxycarbonyl- and 4-phenylazo-pyrazolin-5-ones present the possibility of a fourth tautomer with an exocyclic double bond and a chelated structure. The molecular structure of (138) has been determined by X-ray crystallography (Table 5). It was shown that the hydroxy group participates in an intramolecular hydrogen bond with the carbonyl oxygen atom of the ethoxycarbonyl group at position 4 (8OCSCII21). On the other hand, the fourth isomer is the most stable in 4-phenylazopyrazolones (139), a chelated phenyl-hydrazone structure. 

The Diels-Alder reactions of the methyl or ethyl ester of benzenesulfonylindole-2-acrylic acid with several l-alkoxycarbonyl-l,2-dihydropyridines are reported and only a single stereoisomer was obtained, as in the case of l-methoxy(ethoxy)-carbonyl-1,2-dihydropyridines. However, when the Diels-Alder reaction of 17 was carried out with 8g[R = (CHsjsC], a mixture of two stereoisomers 18gand25were obtained in a 1 1 ratio (65% total yield). The bulky rerr-butyl group creates sufficient steric interference with the indole ring to cause the loss of stereochemistry ... 

Natriumboranat/Aluminiumchlorid wird hauptsachlich zur selektiven Reduktion von Carbonsaureestern gebraucht, die neben der Alkoxycarbonyl-Gruppe noch eine Carboxy-Gruppe (in Form des Natrium-Salzes), eine unsubstituierte Amino-carbonyl-Gruppe, eine Nitro- oder Halogcn-Gruppe enthalten. 

Alkyltriphenylphosphonium halides are only weakly acidic, and a strong base must be used for deprotonation. Possibilities include organolithium reagents, the anion of dimethyl sulfoxide, and amide ion or substituted amide anions, such as LDA or NaHMDS. The ylides are not normally isolated, so the reaction is carried out either with the carbonyl compound present or with it added immediately after ylide formation. Ylides with nonpolar substituents, e.g., R = H, alkyl, aryl, are quite reactive toward both ketones and aldehydes. Ylides having an a-EWG substituent, such as alkoxycarbonyl or acyl, are less reactive and are called stabilized ylides. 

The alkoxycarbonyl protecting groups can also be introduced into amines by, triazolides (Table 4—7). With A-tert-butoxycarbonyl-1,2,4-triazole the tert-butoxy-carbonyl protecting group (Boc) is transferred readily onto amino functions of primary amines, trimethylbenzyl ammonium salts of amino acids, or peptides.[ 1965 Alternatively, the Boc group can be transferred with terf-butylphenylcarbonate in the presence of 1,2,4-triazole. In this latter approach the triazolide is presumably formed as an intermediate. ... 

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). 

Most researchers currently agree that the hydrido mechanism is more common than the alkoxycarbonyl path in the alkoxycarbonylation of alkenes with palladium systems. However, carbalkoxy complexes are putative intermediates in carbonylation reactions giving succinates and polyketone diesters, with metals like Co, Rh, or Pd.137... 

A different result was obtained in the cycloaddition to methylenecyclo-propanes 216-218 tearing alkoxycarbonyl substituents on the cyclopropyl ring. In this instance, 1,2,3-triazoles 220 isomeric with the triazolines 219 were formed in the reaction [57]. The formation of triazoles 220 is rationalised by the intermediate formation of triazolines 219, which are unstable under the reaction conditions and undergo a rearrangement to the aromatic triazoles via a hydrogen transfer that probably occurs with the assistance of the proximal ester carbonyl (Scheme 35). The formation of triazoles 220 also confirms the regio-chemistry of the cycloaddition for the methylene unsubstituted methylene-cyclopropanes, still leaving some doubt for the substituted ones 156 and 157. 

The course of the reductive carbonylation reaction is considered to involve intially the alkoxycarbonyl complex 156, which attacks 150 to form the nickel enolates 157 followed by protonation [81]. (Scheme 56)... 

Pd-catalyzed carbonylation of heteroaryl halides provides a quick entry to heteroaryl carbonyl compounds such as heteroaryl aldehydes, carboxylic acids, ketones, esters, amides, a-keto esters and a-keto amides. In addition, Pd-catalyzed alkoxycarbonylation and aminocarbonylation are compatible with many functional groups, and therefore, are more advantageous than conventional methods for preparing esters and amides [78],... 

Halothiophenes take part in Pd-catalyzed alkoxycarbonylations in the presence of CO, alcohol and base. In order to avoid the inconvenience of pressurized carbon monoxide, alkyl formate may be used as a safe surrogate [130], In one of the many examples, 2-Iodothiophene was carbonylated to the corresponding methyl ester using methylformate in place of CO. 

In 1986, Tsuji et al. developed the palladium(0)-catalyzed alkoxycarbonylation of racemic or achiral propargyl carbonates 128 in an alcohol solvent to afford 131 via carbonylation of 129 to 130 (Scheme 4.35) [55], Palladium(0)-catalyzed alkoxycarbonylation of 134 and isomerization to 136 were key steps for the total synthesis of (-)-kallolide B 138 (Scheme 4.36) [56],... 

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. 

Carbonylation reactions under water-gas-shift conditions have been largely explored, alkynols giving saturated lactones and alkynyl amines giving saturated lactams [43]. Intramolecular alkoxycarbonylations of alkynols producing unsaturated lactones will be further described in the following paragraph. 

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... 

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

Abstract Development in the field of transition metal-catalyzed carbonylation of epoxides is reviewed. The reaction is an efficient method to synthesize a wide range of / -hydroxy carbonyl compounds such as small synthetic synthons and polymeric materials. The reaction modes featured in this chapter are ring-expansion carbonylation, alternating copolymerization, formylation, alkoxycarbonylation, and aminocarbonylation. 

A wide range of organic substrates can undergo an oxidative carbonylation reaction. Depending on reaction conditions, alkenes have been converted into -chloroalkanoyl chlorides (oxidative chloro-chlorocarbonylation) [1,2], succinic diesters (oxidative dialkoxycarbonylation) [3-20], a,/J-unsaturated esters [21,22] (oxidative monoalkoxycarbonylation), or /J-alkoxyalkanoic esters [11] (oxidative alkoxy-alkoxycarbonylation), according to Eqs. 10-13. 

Ketones can be oxidatively carbonylated at the a-carbon via enol intermediates using PdCl2 as the catalyst and Q1CI2 as oxidant [122], The initially formed carbonylation products correspond to a-chlorination and a-alkoxycarbonylation. Under the reaction conditions, these compounds undergo further transformations involving C - C cleavage eventually leading to a mixture of esters and an alkyl chloride or (in the case of cyclic ketones) to a diester and a chloroester (Schemes 20-21). 

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]. 

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. 

Of particular interest was the carbonylation of (Z)-2-en-4-yn-l-ols and (Z)-(2-en-4-ynyl)amines, which afforded furan-2-acetic [104,105] and pyrrole-2-acetic [116] esters, respectively, in good yields, through spontaneous or acid-promoted aromatization of the initially formed ( )-2-(alkoxycarbonyl)-methylene-2,5-dihydro-furans or -pyrroles (Scheme 31). 

A suitably placed carbonyl oxygen can also act as intramolecular nucleophile in Pdl2/KI-catalyzed oxidative cyclization-alkoxycarbonylation re-... 

In the case of acetylenic amides, the carbonyl oxygen atom turned out to be nucleoplilic enough to directly attack the coordinated triple bond, owing to the conjugation with the amide moiety. Thus, cGa-dialkyl substituted 2-ynylamides smoothly underwent oxidative cyclization-alkoxycarbonylation to afford new oxazoline derivatives in good yields (Eq. 44) [102,113]. 

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