Allylation enolates

Allylic ethers of enols (allylic vinylic ethers) also undergo the Claisen rearrangement 501 in fact, it was discovered with these compounds first 502... 

Although the Claisen rearrangement was first observed in the enol allyl ethers,1-2 the reaction is much more useful and important in the aromatic series. Some interesting observations have been made, however, with the open-chain systems. The original reports concerned the rearrangement of ethyl O-allylacetoacetate, O-allylacetylacetone (XIVo), and O-allyloxymethylenecamphor (XV). 

The preparation of a-selenoketones, esters, nitriles and related compounds can easily be performed via alkylation of the corresponding enolates or stabilized carbanions [21]. These compounds have found many synthetic applications in radical chemistry. In Eq. (9), a typical example involving a ketone is depicted [22]. The stability of a-selenoketones such as 41 is remarkable. Similar reactions with lactones have been performed. For instance, this approach has been applied to the stereoselective synthesis of oxygen-containing rings to either faces of a bicyclic structure [23]. The approach based on a-selenenylation/radical allyla-tion compares favorably with classical enolate allylation procedures, which usually leads to mixture of mono- and diallylated compounds. Furthermore, this strategy is excellent for the preparation of quaternary carbon centers [24] as shown by the conversion of 43 to 45, a key intermediate for the synthesis of fredericamycin A, [Eq. (10)] [25]. Similar reactions with sulfoxides [26] and phosphonates [27] have also been reported. 

Dehydrodimerization of Cyclic Enol/Allyl Ethers and Olefins... 

R-M Organo- metallics CHjLi CHaMgl (CH3)2Cu-Li+ The more ionic RM bond is more reactive Substitutions Additions. Deprotonates acidic H s See enolates (allylic sources)... 

C=C-Z Allylic sources Enolates C=C-0 Enamines C=C-NR2 Enol ethers C=C-OR The better donor on the pi bond is more reactive Substitutions Additions. Carbon vs. heteroatom decision Extended enolates. Allylic alkyne sources... 

The carbon-carbon bond-forming step of the acid-catalyzed aldol reaction has an enol (allylic source) attacking a protonated carbonyl (which is just a lone-pair-stabilized carbocation). With those hints, give a mechanism for the acid-catalyzed aldol reaction. 

Shortly after Stoltz s report, Trost also showed that Pd catalysis in presence of Trost ligands such as 26 could also convert a wide variety of enol allyl carbonates into ketones with quaternary centers at the a-position in an analogous manner to that demonstrated in equation 12.34. In almost all cases reported, both yield and % ee values were high. 

We call this disconnection enolate allylation because we want to alkylate an enolate ion with an allyl halide. We have already discussed (chapter 19) the regioselectivity problems inherent in reactions of allyl derivatives and you should recall that we want to react at the correct (less substituted) end of the allyl system and we want to make an f-alkcnc. The solution is to use a [3,3]-sigmatropic rearrangement. This is the reaction sequence ... 

The hemiacetal 169 was first oxidised to the lactone 176 and the lithium enolate allylated with the expected stereoselectivity to give 177 and then, by a series of reactions described in the workbook, into the aldehyde 178. 

In 1912 Claisen observed the rearrangement of enol allyl ethers to C-allyl compounds, e.g., with acetoacetic ester and acetylacetone 81... 

B. Dehydrodimerization of cyclic enol/allyl ethers and olefins... 

The Wacker reaction provides a method for the preparation of 1,4-dicarbonyl compounds, by formation of an enolate, allylation with an allyl halide, followed by palladium-catalysed oxidation of the terminal alkene. The product 1,4-dicarbonyl compounds can be treated with base to promote intramolecular aldol reaction (Robinson annulation - see Section 1.1.2) to give cyclopentenones. Thus, in a synthesis of pentalenene, Wacker oxidation of the 2-aUyl ketone 115 gave the 1,4-diketone 116, which was converted to the cyclopentenone 117 (5.115). ... 

With the notable exceptions of aUyl-allyl coupling (Sect, in.2.10) and enolate allylation (Sect. V.2.1.4), Pd-catalyzed allylation has been achieved mostly with alkenyl-metals (alkenyl-allyl couphng) and arylmetals (aryl-aUyl couphng). The use of alkylmetals and alkynyhnetals has been rare perhaps because their allylation can be performed satisfactorily with appropriate Grignard reagents, whose reactivity can be modified favorably with either stoichiometric or catalytic amounts of Cu compounds, as needed. 

This section includes the synthesis and structures of bothC-bound and Obound transition metal enolate complexes. Reviews of reactions catalyzed by Lewis acidic, early metal enolate intermediates have been published. Cross-couphng of enolates is described in Qiapter 19. Additional reactions of enolate nucleophiles, such as enolate allylation, are ttiought to occur by external attack of the enolate nucleophile on -ir-ligands and are described in Chapters 11 and 20. Late transition metal enolate complexes undergo a number of the classes of stoichiometric reactions presented in Chapters 3-12 of this text, including 3-hydride elimination to produce enones, - insertion of unsaturated ir-systems, and reductive eluninations. - - - ... 

The advent of the catalytic Tsuji-Trost reaction in the early 1970s " (Sects. V.2.1.1 and V.2.1.2) has significantly expanded the scope of enolate allylation and related reactions. Noteworthy among others is that the range of allylic electrophiles was vastly expanded from allylic halides, such as chlorides and bromides, to a much wider range of derivatives including not only halides but also O, S, N, and other heteroatom-containing derivatives. Curiously, however, the scope of the Tsuji-Trost reaction had essentially been limited to the Pd-catalyzed allylation of extra-stabilized enolates, such as those derived from malonate and acetoacetate esters, until around 1980. 

Although outside the scope of this section, the concurrent development of the Pd-catalyzed allylation of /3-ketocarboxylic acids via the formation and decomposition of allyl /3-ketocarboxylates is noteworthy (Sects. V.2.1.1 and V.2.1.2). The mechanism shown in Scheme 4, which involves (i) oxidative addition of allyl /3-ketocarboxylates, (ii) decarboxylation, and (iii) intermolecular enolate allylation was proposed and experimentally supportedUnfortunately, a-allylation with y-disubstituted allyl derivatives, such as geranyl carboxylates, proceeds in low yields, and there are some indications that the reaction may lack some specificity features, for example, stereospecificity of the allylic moiety. 

Enolate Allylic Electrophile Other Conditions Yield (%) Comments Reference... 

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