Allyl enol carbonates, decarboxylation

The decarboxylation-allylation of allyl enol carbonates proceeds smoothly[450]. The isomeric enol carbonates 699 and 701 of the enone 698 undergo regiospecific allylation, giving the regioisomers 700 and 702 selectively. 

Allyl enol carbonates derived from ketones and aldehydes undergo Pd-cat-alyzed decarboxylation-elimination, and are used for the preparation of o, /3-unsaturated ketones and aldehydes. The reaction is regiospecific. The regio-isomeric enol carbonates 724 and 726, prepared from 723, are converted into two isomeric enones, 725 and 727. selectively. The saturated aldehyde 728 can be converted into the a,/3-unsaturated aldehyde 730 via the enol carbonate 729[459]. 

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. ... 

As an alternative to prior deprotonation of the parent carbonyl compounds, enolates can also be generated in situ from allyl /(-koto carboxylates or allyl enol carbonates by decarboxylation with simultaneous production of a 7i-allylpalladium complex 1-12. A similar utilization of / -keto acids has also been described13. The following diagram illustrates the reaction course for an allyl jS-keto carboxylate. 

In order to achieve regio- and stereoselective a-allylation of a cyclohexanone derivative, Paquette and Nicolaou carried out the Pd-catalyzed decarboxylation-allyladon of the allyl enol carbonate 578 at room temperature to give the allyl ketone 579 in 58% yield and a regioisomer (24%) using PPh3 [208]. 

As a final set of examples, enantioselective allylic substitution of unstabilized eno-lates to form a new stereocenter at the enolate carbon have been developed through the decarboxylative reactions of allyl enol carbonates. - - These reactions are enantioselective versions of reactions closely related to those in Equation 20.18 and Scheme 20.4, and two examples are shown in Equations 20.60 and 20.61. In these cases, a new stereocenter is formed at the a-carbon of the enolate nucleophile. Most of these reactions have been conducted with allyl enol carbonates that generate cyclic ketone enolates, but enantioselective reactions of acyclic allyl enol carbonates have also been reported. Although allyl enol carbonates undergo decarboxylation faster than the 3-keto ester isomers, the 0-allyl p-keto esters are more difficult to prepare, and enantioselective allylations starting with p-ketoesters have been reported. - Decarboxylative reactions of amines and a-amino acids have been conducted to form allylic and homoallylic amines (Equation 20.62), respectively, and enantioselective decarboxylative allylations of amides have been reportedIridium-catalyzed enantioselective decarboxylative allylation of amides starting with 0-allyl imides has also been reported. ... 

The use of palladium(II) 7i-allyl complexes in organic chemistry has a rich history. These complexes were the first examples of a C-M bond to be used as an electrophile [1-3]. At the dawn of the era of asymmetric catalysis, the use of chiral phosphines in palladium-catalyzed allylic alkylation reactions provided key early successes in asymmetric C-C bond formation that were an important validation of the usefulness of the field [4]. No researchers were more important to these innovations than Prof. B.M. Trost and Prof. J. Tsuji [5-10]. While most of the early discoveries in this field provided access to tertiary (3°) stereocenters formed on a prochiral electrophile [Eq. (1)] (Scheme 1), our interest focused on making quaternary (4°) stereocenters on prochiral enolates [Eq. (2)]. Recently, we have described decarboxylative asymmetric allylic alkylation reactions involving prochiral enolates that provide access to enantioenriched ot-quatemary carbonyl compounds [11-13]. We found that a range of substrates (e.g., allyl enol carbonates,... 

Decarboxylation of Carboxylic Acids and Derivatives.—A palladium-catalysed decarboxylation-dehydrogenation of allyl P-keto-carboxylates and allyl enol carbonates occurs in good yield for ten examples however, mixtures of isomers are obtained in some cases (Scheme 32). ... 

Allyl /3-keto carboxylates and allyl enol carbonates undergo a palladium-catalyzed decarboxylation-dehydrogenation to yield o, S-unsaturated ketones in usually high chemical yield and with good selectivity. Following this approach, it was possible to obtain 2-methyl-2-cyclopentenone in two steps from diallyl adipate in a procedure that could be convenient for large-scale preparations (eq 62). ... 

Scheme 5.30 Mechanistic pathways in the palladium-catalyzed decarboxylative allylic alkylation, starting from allyl p-keto esters 91 or allyl enol carbonates 92.

Scheme 5.32 Enantioselective decarboxylative allylic alkylations, starting from allyl enol carbonates 101 (reported by Stoltz) and allyl enol carbonates 103 (reported by Trost).

Whereas allyl enol carbonates are prochiral starting materials, the fi-keto esters are frequently chiral but can be used as racemic compounds because the stereogenic center vanishes in the course of the decarboxylative allylic alkylation, precisely during the formation of the enolate. In general, both enantiomers of chiral fi-keto esters 91 react without enantiodifferentiation with the palladium(O) catalyst to give the enolate, a course of the reaction that was termed stereoablative... 

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 most common nucleophiles employed in the allylic alkylation are soft species such as malonate esters. However, Trost and Schroeder have discovered that high ees can be achieved in the addition of cyclic lithium enolates using ligand (10.54) with one equivalent of trimethyltin chloride, which may act to soften the nucleophilic species by transmetaUation to the tin enolate. Enantioselective additions of nonstabilised ketone enolates can also be achieved using an alternate palladium-catalysed decarboxylation protocol. In this approach an allyl 3-ketoester (10.72) or allyl vinyl carbonate (10.73) undergoes decarboxylation in the presence of Pd(0) to... 

Allyl y3-keto carboxylates 563 undergo facile Pd-catalyzed decarboxylation to form either jr-allylpalladium enolates 565 or a-palladaketone 564. Also rr-allyl-palladium enolates are generated from enol carbonates 566. As summarized below, several transformations to afford 567-573 are possible under different but proper conditions depending on the substituents R [199]. In addition to allyl j6-keto carboxylates, other allyl esters such as allyl malonates, cyanoacetates and nitroacetates undergo similar transformations. With these Pd-catalyzed reactions, a new generation of j6-keto esters and malonate chemistry has been developed. 

As for the original allylation reaction, decarboxylative allylation may be made asymmetric by the inclusion of chiral ligands (Scheme 9.64). Similar results are obtained using either the 3-ketoester 9.238 or the enol carbonate 9.237 (Scheme 9.65). ... 

Scheme 5.44 Enantioselective formation of butenolides 133 by palladium-catalyzed decarboxylative allylic alkylation of furan-derived enol carbonate 132.

Trost BM, Bream RN, Xu J. Asymmetric allylic alkylation of cyclic vinylogous esters and thioesters by Pd-catalyzed decarboxylation of enol carbonate and beta-ketoester substrates. Angew. Chem. Int. Ed. 2006 45 3109-3112. 

In addition, unstabilized enolate nucleophiles have been generated by decarboxylation of (3-ketocarboxylates. In this case, no additives are required to activate the nucleophile, but the highest yields and selectivities were obtained in the presence of two equivalents of DBU [82]. Although reactions of allylic carbonates containing aromatic, heteroaromatic, and aliphatic substituents occurred, only reactions to form aryl ketone products were published. 

The mechanisms proposed for these reactions are all quite analogous, and only the intramolecular cases will be considered in detail (Scheme 5). Oxidative addition by Pd° into the allylic C—O bond of the allyl 0-ketocaiboxylate produces an allylpalladium caxboxylate. This species then undergoes decarboxylation to yield an allylpalladium enolate (oxa-ir-allyl), which subsequently eliminates a 0-H to form the enone and provide an allyl-Pd-H. Reductive elimination from the allyl-Pd-H yields propene and returns Pd to its zero oxidation state. A similar mechanism can be imagined for the alkenyl allylcarbonate. Oxidative addition by the Pd° forms an allylpalladium carbonate, which decarboxylates again to give an allylpalladium enolate (oxa-ir-allyl). 0-Hydride elimination and reductive elimination complete the process. The intermolecular cases derive the same allylpalladium enolate intermediates, only now as the result of bimolecular processes. 

Needless to say, /i-keto esters are important compounds in organic synthesis. Their usefulness has been considerably expanded, based on Pd-catalysed reactions of allyl / -keto carboxylates 399. Cleavage of the allylic carbon-oxygen bond and subsequent facile decarboxylation by the treatment of allyl / -keto carboxylates with Pd(0) catalysts generate the 7i-allylpalladium enolates 400, 401. These intermediates undergo, depending on the reaction conditions, various transformations which are not possible by conventional methods. Thus new synthetic uses of / -keto esters and malonates based on Pd enolates have been expanded. These reactions proceed under... 

Keto stannylenolates can be prepared by the reaction of Sn-O or Sn-N bonded compounds with diketene, which can be regarded as a cyclic enol ester. The adducts formed from bis(tributyltin) oxide can undergo further reaction, with subsequent decarboxylation, to give the same products as those from the simple enolates. Alkylation with alkyl iodides or benzyl or allyl bromides is strongly catalysed by lithium bromide (e.g. Scheme 14-5). Double alkylation can be achieved with HMPA as solvent.120 The product of alkylation before the final hydrolysis is itself a tin enolate, which can be used in reactions with further carbon electrophiles. 

By far, the most often used nucleophiles are malonates, which can be deproto-nated by the aUcoxide formed in the reaction of allyl carbonates or by an added base such as NaH. This standard nucleophile has been applied in all types of aUylations, and many applications are also reported in this monograph. The nucleophihc species can also be generated by 1,4-addition, for example, of alkoxides, generated from carbonates, onto alkylidenemalonates both inter- and intramolecularly [92]. The substitution products can be subjected to a thermal desalkoxycarboxylation or, after hydrolysis, decarboxylation, giving rise to carboxylic esters or acids [93]. Therefore, in combination with this decomposition, malonates can also be used as surrogates for ester enolates [94], which generally cannot be used as nucleophiles in allylations. 

According to a tentative mechanism as represented by the above (simplified) catalytic cy-de, the propargyl carbonate is transformed to a Pd-intermediate 90, which decarboxylates to the allenic moiety 93 after addition of the enolate of acetoacetate ( 92) and isomerization (92 91), the iT-allyl-Pd complex 91 cyclizes to the product 89. Highly functionalized tetrasubstituted furans can be prepared by a novel Pd-catalyzed three-component cycliza-tion of 2-alkinyl-2-alken-l-ones with an allyl chloride and an alcohol [30]. 

---