Decarboxylation allyl /1-keto esters

Ring expansion (1, 369-370 6, 252-253). The ring expansion of ketones to the next higher homolog with ethyl diazoacetate requires hydrolysis and decarboxylation of the intermediate 8-keto ester, a step that is sometimes troublesome. Baldwin and Landmesser have used benzyl diazoacetate and allyl diazoacetate as alternative reagents. The benzyl jS-keto esters are cleaved and decarboxylated on hydrogenation both benzyl and allyl keto esters are reduced by sodium in liquid ammonia to ketones. 

Hydrolysis of the dialkylated jS-keto esters and malonates is not easy, and usually harsh conditions are required. Also decarboxylation occurs only at high temperature. On the other hand, hydrolysis and decarboxylation reactions of substituted allyl -keto esters and allyl malonates using Et3N-HC02H proceed at room temperature under neutral conditions. THP-protected allyl jS-keto ester 597 was converted to 598 at room temperature without deprotection of THP [213]. The free mono-carboxylic acid 600 was obtained smoothly from the disubstituted diallyl malonate 599 [214]. 

An interesting strategy for convergent steroid synthesis has been reported by Deslongchamps based on Pd-catalyzed decarboxylation-Michael addition of allyl -keto ester (bicyclic Nazarov reagent) 605 to cyclohexanone 604. The first intermolecular Michael addition of the Pd-enolate, generated from 605, to 604 afforded 606. Further intramolecular Michael addition constructed the steroid skeleton 607, and the tetracycle 608 was obtained by jS-H elimination [218]. 

Other Methods. - One of the most important and flexible approaches to ketone synthesis involves the manipulation of 6-keto-esters. Tsuji et al. have reported that the use of allyl keto-esters, which are prepared from ketones and diallyl carbonate or allyl chloroformate, offer advantages over more common esters in that the ester hydrolysis/decarboxylation step... 

Pd(0) species can catalyse the decarboxylation of allyl -keto-esters e.g. 48) to give ketones (49). The reactions are efficient for cyclohexanones but much less so with acyclic esters. Examples with other ring sizes were not reported. 

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]. 

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... 

Quaternary stereocentres in /3-keto esters have been deracemized in an enantio-convergent decarboxylative allylation process, catalysed by palladium(II).202 One catalyst is involved in both C-C bond-breaking and -making steps. 

The ruthenium complex Cp Ru(bipyridyl)Cl has been developed as a catalyst for the first regioselective tandem Michael addition-allylic alkylation of activated Michael acceptors. The net outcome is the decarboxylative insertion of Michael acceptors into allyl /3-keto esters to produce (215). The reaction combines the generation of Ru-tt-allyl and enolate from (213) the enolate is first added to the Michael acceptor (214) and the resulting species is captured by the Ru-tt-allyl.254... 

Tsuda et al. have continued their studies on the palladium(0) catalysed decarboxylative allylation of 0-keto esters and 0-keto... 

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]. 

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. 

Fig. 4.3 Scope of the decarboxylative asymmetric allylic alkylation using p-keto esters...

Our synthesis of the 7-hydroxy-substituted isoflavanones la-e had to take into account protection of hydroxy group due to the likely interference with the synthetic route and in particular the key decarboxylative asymmetric protonation step. The synthesis of la-c could be accomplished by a series of Pb-mediated arylations of allyl-P-keto ester 7. This was accessed by Friedel-Crafts acylation, cyclization, NAP-protection and subsequent acylation with allyl cyanoformate (Scheme 5.2) [19-21]. We were able to generate isoflavanone precursors 8a-e from the allyl-P-keto ester (7) by introducing various aryl groups through the use of... 

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. ... 

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