Oxidation 1,3-dicarbonyls

The second type is oxidative dicarbonylation of acetylene with PdCb in benzene, which produces chlorides of maleic, fumaric and muconic acids [130], Methyl maleate (215), fumarate (216) and muconate (217) are obtained in MeOH containing thiourea by passing acetylene and oxygen in the presence of a catalytic amount of PdCb [131]. 

Formation of these products can be understood by assuming that the carbonylation of propargyl alcohol under high pressure involves two different reaction pathways. One is the Pd(0)-catalyzed carbonylation and the other is the Pd(II)-catalyzed oxidative carbonylation 2,3-Butadienoate (80) is a primary product of the Pd(0)-catalyzed carbonylation, but further attack by carbon monoxide at the central sp carbon of 80 under high carbon monoxide pressure yields itaconate (81) as the dicarbonylation product. Formation of aconitate (83) is explained by the oxidative dicarbonylation of a triple bond with Pd(II) species, followed by Pd(0)-catalyzed allylic carbonylation. As a supporting evidence, methyl aconitate (83) was... 

Palladium/graphite in combination with copper(ll) chloride and flthium chloride is a good catalytic system for the oxidative dicarbonylation of alkenes using a 20 1 ratio of CO/O2 (Eq. 16). The ratio of diester to dimethyl carbonate is sensitive to the nature of the palladium catalyst precursor (Pd/graphite or PdCl2). 

The oxidative dicarbonylation of 1,3-butadiene to generate dimethyl hex-3-ene-l, 6-dioate resulted using Pd/graphite, in combination with CUCI2 and LiCl (Eq. 20). ... 

Oxidative carbonylation was coupled with reduction to afford catalytic carbonylation (see also Sect. VI.4.4.2). Thus, the diethylacetal of 2-propynal was carbonylated in a 65% yield by combining oxidative dicarbonylation and reductive splitting of an ethoxy group (Scheme 34). 

These reactions are likely to be initiated by Pd—CO2H species, formed by H2O attack on coordinated CO (Scheme 4). Formation of the maleic anhydrides corresponds to oxidative dicarbonylation and occurs with elimination of Pd(0), so the presence of an external oxidant such as O2 is required to make the process catalytic. On the other hand, a Pd—H species [in equilibrium with Pd(0) + H+] may be responsible for double bond reduction leading to succinic anhydrides. 

Cyclocarbonylation of unsaturated substrates incorporating a nucleophilic function (—YH) in a suitable position can also be effected in the presence of external nucleophiles (ZH) such as alcohols. These reactions usually result in oxidative dicarbonylation of the unsaturated bond and are promoted by Pd(ll) species. As ensuing dicarbonylation Pd(ll) is reduced to Pd(0), the presence of an oxidant is needed in order to make the process catalytic, as exemplified in Scheme 18 in the case of triple bond. 

Endoperoxides (also 1,2-dioxetanes) are versatile starting materials for further transformations. In view of the weak 0-0 bond, these peroxides are thermally sensitive to homolytic cleavage, a feature that makes most of them ha2aidous. Ring opening opens up attractive opportunities for selective transformations that include reductions (diols), oxidations (dicarbonyl products), rearrangements (hydroxy carbonyl compounds, epoxy carbonyl compounds, fo/s-epoxides, ene diones, etc.) and additions (polycycKc dioxanes or trioxanes, some of which display antimalarial activity). The synthesis and the subsequent reactions of the 2,3-dioxabicyclo[2.2.2]oct-7-en-5-one skeleton have been studied by Adam etak An impressive number of chemical transformations and examples for applications in organic synthesis have been collected in several reviews. 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Treatment of O-silyl enols with silver oxide leads to radical coupling via silver enolates. If the carbon atom bears no substituents, two such r -synthons recombine to symmetrical 1,4-dicarbonyl compounds in good vield (Y. Ito, 1975). 

Cyclohexene derivatives can be oxidatively cleaved under mild conditions to give 1,6-dicarbonyl compounds. The synthetic importance of the Diels-Alder reaction described above originates to some extent from this fact, and therefore this oxidation reaction is discussed in this part of the book. 

Pyrroles from 1,4-dicarbonyl compounds and ammonia isoxazolines from olefins and nitrile oxides. 

Several 1,4-dicarbonyl compounds are prepared based on this oxidation. Typically, the 1,4-diketone 10 or the 1,4-keto aldehyde 12 can be prepared by the allylation of a ketone[24] or aldehyde[61,62], followed by oxidation. The reaction is a good annulation method for cyclopentenones (11 and 13). Syntheses of pentalenene[78], laurenene[67], descarboxyquadrone[79], muscone (14 R = Me)[80]) and the coriolin intermediate 15[71] have been carried out by using allyl group as the masked methyl ketone (facing page). 

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... 

Oxidative carbonylation of alcohols with PdCh affords the carbonate 572 and oxalate 573(512-514]. The selectivity of the mono- and dicarbonylation depends on the CO pressure and reaction conditions. In order to make the reaction catalytic, Cu(II) and Fe(III) salts are used. Under these conditions, water is formed and orthoformate is added in order to trap the water. Di-/-butyl peroxide is also used for catalytic oxidative carbonylation to give carbonates and oxalates in the presence of 2,6-dimetliylpyridine(515]. 

Cyclic diols give dicarbonyl compounds The reactions are faster when the hydroxyl groups are cis than when they are trans but both stereoisomers are oxidized by periodic acid... 

The conversion of furans by oxidative acetylation or methoxylation to 2,5-diacetoxy- or 2,5-dimethoxy-2,5-dihydrofurans respectively, and their subsequent hydrogenation to the corresponding tetrahydrofurans, provides a useful source of protected 1,4-dicarbonyl compounds capable of conversion inter alia into the other five-membered heterocycles [Pg.142]

This 1,3-migration of hydrogen was also observed when 40 reacted with Lawesson s reagent to produce the dithiolactone 41. However, when y-hydroxy-a,P-unsaturated aldehyde 42 was reacted under similar conditions, thiophene 43 was prepared efficiently. These results are not surprising considering that the oxidation state of 42 is equivalent to the traditional saturated 1,4-dicarbonyl substrates of the Paal thiophene reaction via tautomerization of the double bond, and aromaticity is reestablished in the fully conjugated 43. 

The Hantzsch pyridine synthesis involves the condensation of two equivalents of a 3-dicarbonyl compound, one equivalent of an aldehyde and one equivalent of ammonia. The immediate result from this three-component coupling, 1,4-dihydropyridine 1, is easily oxidized to fully substituted pyridine 2. Saponification and decarboxylation of the 3,5-ester substituents leads to 2,4,6-trisubstituted pyridine 3. 

---