Decarboxylation, allylic acetates reaction

Wylation under neutral conditions. Reactions which proceed under neutral conditions are highly desirable, Allylation with allylic acetates and phosphates is carried out under basic conditions. Almost no reaction of these allylic Compounds takes place in the absence of bases. The useful allylation under neutral conditions is possible with some allylic compounds. Among them, allylic carbonates 218 are the most reactive and their reactions proceed under neutral conditions[13,14,134], In the mechanism shown, the oxidative addition of the allyl carbonates 218 is followed by decarboxylation as an irreversible process to afford the 7r-allylpalladium alkoxide 219. and the generated alkoxide is sufficiently basic to pick up a proton from active methylene compounds, yielding 220. This in situ formation of the alkoxide. which is a... 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

Activated methylene compounds such as dimethyl malonate have found substantial utility in palladium catalyzed allylic substitution reactions. Accordingly, the Krapcho decarboxylation is often used in conjunction with these reactions. As an example, the first total synthesis of enantiomerically pure (-)-wine lactone has utilized the sequence of reactions.27 First, the allylic substitution reaction of 2-cyclohexen-l-yl acetate (49) with alkali sodium dimethylmalonate yielded 51 with high enantioselectivity, as a result of the use of chiral phosphine ligand 50. The malonate was then subjected to Krapcho decarbomethoxylation using NaCl, H2O, and DMSO at 160 °C to yield 52. This reaction has been used similarly following the allylic substitution reaction with other malonate derivatives.28-30... 

Formates. The decarboxylation reaction of metal formates is a fairly general route for the synthesis of metal hydrides and it has been applied to many transition metals. As an example, allyl palladium formates, which are believed to be intermediates in the catalytic reductive cleavage of allylic acetates and carbonates with formic acid to give monoolefins (Scheme 6.32), have been synthesized. In fact the complexes undergo decarboxylation and the reductive elimination of the allyl hydrido fragments, supporting the catalytic cycle proposed [105]. 

Several 1,3-diene syntheses involving elimination reactions that are catalyzed by Pd(Ph3P)4 have been reported. The first involves the Et3N mediated elimination of HOAc from allylic acetates in refluxing THF. A complementary procedure involves the Pd(Ph3P)4 catalyzed decarboxylative elimination of /3-acetoxy-carboxylic acids (eq 46). The substrates are easily prepared by the condensation of enals and carboxylate enolates irrespective of the diastereomeric mixture, ( )-alkenes are formed in a highly stereocontrolled manner. The geometry of the double bond present in the enal precursor remains unaffected in the elimination and the reaction is applicable to the formation of 1,3-cyclohexadienes. 

Allylic carbonates are more reaetive than acetates. In addition, reaction of carbonates proceeds in the absence of bases [6]. Formation of jr-allylpalladium 9 from allyl methyl carbonates 8 proceeds by oxidative addition, followed by decarboxylation, and TT-allylpalladium methoxide 9 is generated at the same time, which abstracts a proton from a pronucleophile to form 10. In situ formation of methoxide is a key in the allylation under neutral conditions. Allylation under neutral conditions is useful for the reaction of base-sensitive compounds. For example, exclusive chemoselective reaction of the carbonate group in 4-acetoxy-2-butenyl methyl carbonate (11) occurred in the absence of a base to yield 12. Similar chemoselective reaction of the allyl carbonate group in the chiral cyclopentenyl methyl carbonate 13 with the jS-keto ester 14 without attacking the allylic acetate group to give 15 was observed even in the presence of NaH. As expected, retention of stereochemistry (see Chapter 4.2.1) was observed in this substitution [7]. 

Reactions that proceed under neutral conditions are highly desirable. An important event in TT-allylpalladium chemistry is the introduction of highly reactive allylic carbonates (Sect. V.2.1.3), Their reactions can be carried out under mild neutral conditions. " Also, reactions of allylic carbamates, " allyl aryl ethers, and vinyl epoxides proceed without addition of bases. As shown by the mechanism in Scheme 6, the oxidative addition of allyl methyl carbonates is followed by decarboxylation as an irreversible process to afford TT-allylpalladium methoxide, and the generated methoxide picks up a proton from pronucleophiles (NuH), such as active methylene compounds. This in situ formation of the alkoxide is the reason why the reaction of aUyl carbonates can be carried out without addition of bases from outside. Alkoxides are rather poor nucleophiles, and alkyl allyl ethers are not formed from them. In addition, formation of TT-allylpalladium complexes from allylic carbonates involving decarboxylation is irreversible. In contrast, the formation of TT-allylpalladium acetate from allyl acetate is reversible. 

Unsaturated carboxylic adds (23) can be electrolytically decarboxylated to allylic acetates (24) in 80—90% yield. a-Phenylthiocarboxylic acids can also be decarboxylated electrolytically to give high yields of aldehyde acetals (c/. 3, 49). Electrolytic procedures are also useful for the conversion of malonic acids into ketones. " This method has been used to prepare valerolactones from cyclic ethers (25), themselves prepared by Diels-Alder reactions between dienes and ketomalonates. ... 

In an extension of previous work, it has been found that Pd(0)-catalysed intramolecular cyclization of allylic acetates (21) can be used to prepare the chrysanthemic acid analogues (22). The potentially useful cw-cyclopropane (23) can be simply obtained by base-induced addition of cyanoacetate to ethyl 2-bromo-3,3-dimethylacrylate followed by decarboxylation oddly, a similar reaction using malonate fails to give a cyclopropane. Optically pure dichloro cw-chrysanthemic acid (26) has been obtained by a Favorskii rearrangement of the chiral cyclobutanone (25) prepared from the keten (24) by sequential [2 + 2]cycloaddition, cine-rearrangement, and resolution (Scheme 3). ... 

Co-adsorption experiments show a complex role of the nature and concentration of chemisorbed ammonia species. Ammonia is not only one of the reactants for the synthesis of acrylonitrile, but also reaction with Br()>nsted sites inhibits their reactivity. In particular, IR experiments show that two pathways of reaction are possible from chemisorbed propylene (i) to acetone via isopropoxylate intermediate or (ii) to acrolein via allyl alcoholate intermediate. The first reaction occurs preferentially at lower temperatures and in the presence of hydroxyl groups. When their reactivity is blocked by the faster reaction with ammonia, the second pathway of reaction becomes preferential. The first pathway of reaction is responsible for a degradative pathway, because acetone further transform to an acetate species with carbon chain breakage. Ammonia as NH4 reacts faster with acrylate species (formed by transformation of the acrolein intermediate) to give an acrylamide intermediate. At higher temperatures the amide may be transformed to acrylonitrile, but when Brreform ammonia and free, weakly bonded, acrylic acid. The latter easily decarboxylate forming carbon oxides. 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

The procedure described illustrates a new general synthetic method for the preparation of (E)-3-allyloxyacrylic acids and their conversion to a-unsubstituted y,6-unsaturated aldehydes by subsequent Claisen rearrangement-decarboxylation. Such aldehydes are traditionally prepared by Claisen rearrangements of allyl vinyl ethers. Allyl vinyl ethers are typically prepared by either mercury-catalyzed vinyl ether exchange with allylic alcohols or acid-catalyzed vinylation of allylic alcohols with acetals. The basic conditions required for alkoxide addition to the betaine to produce carboxyvinyl allyl ethers, as described in this report, nicely complements these two methods. In addition, this Claisen rearrangement is an experimentally very simple procedure, since sealed tube and other high pressure vessels are not required. The allyloxyacrylic acids are heated neat (in most cases a small amount of hydroquinone is added) and, by adjusting the pressure at which the reaction is performed, the aldehyde products distill from the reaction mixture in analytically pure form. 

Considerable use has also been made of allyl carbonates as substrates for the allylation of Pd enolates.9 The reaction of Pd° complexes with allyl enol carbonates119,120 proceeds by initial oxidative addition into the allylic C—O bond of the carbonate followed by decarboxylation, yielding an allylpalladium enolate, which subsequently produces Pd° and the allylated ketone (equation 22). In like fashion, except now in an intermolecular sense, allyl carbonates have been found to allylate enol silyl ethers (equation 23),121 enol acetates (with MeOSnBu3 as cocatalyst) (equation 24),122 ketene silyl acetals (equation 25)123 and anions a to nitro, cyano, sulfonyl and keto groups.115,124 In these cases, the alkoxy moiety liberated from the carbonate on decarboxylation serves as the key reagent in generating the Pd enolate. 

The palladium-catalyzed decarboxylative coupling of allyl 2-(benzo[c(jthiazol-2-yl)acetates 118 provides a facile approach to 2-(but-3-enyl)benzo[c(jthiazoles 122 <07JA4138>. The reaction is initiated by nucleophilic attack of Pd(0) on the allyl ester to give Pd-7t-allyl complex 119, which undergoes nucleophilic attack at the less substituted allylic carbon from the benzothiazole nitrogen to produce 120. Decarboxylative dearomatization leads to intermediate 121, and a subsequent aza-Cope rearrangement driven by rearomatization affords the final product 122 and accounts for the unusual regioselectivity. This appears to be the first report of a tandem allylation/aza-Cope reaction driven by decarboxylative dearomatization/ rearomatization. 

Enol carbonates react with alkylating agents in the presence of a palladium catalyst. The decarboxylative alkylation of allyl enol carbonates to the corresponding aUylcyclohexanone derivatives is known as the Tsuji alkylation. An asymmetric version of this reaction has been reported. The same reaction can be done using enolate anion and aUylic acetates with a palladium catalyst. ... 

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