Allylation of active methylene compound

Allylic carbonates show high reactivity in a related palladium catalyzed decarboxylative allylation of active methylene compounds (equation II). In this case,... 

Solvent Controlled Mono- and Bis-allylation of Active Methylene Compounds... 

The allylation of active methylene compounds with allyl alcohols or their derivatives, called the Tsuji-Trost reaction, is a widely used process in academia as well as in industry. Ranu et al. have reported that the reaction of active methylene compounds with allyl acetate catalyzed by palladium(O) nanoparticles (Scheme 5.22) led to mono-allylation in water, whereas the reaction in THF provided the bis-allylated product. This is a remarkable example of controlling the direction of a reaction by water. 

Allylation. Linear products are obtained from the Ru-catalyzed allylation of active methylene compounds (deprotonated by LiHMDS) with either primary or secondary allylic acetates. A suitable ligand for the Ru metal is o-diphenylphosphinobenzoic acid. 

Allylations. Allylation of enamines with 1-allylbenzotriazoles is accomplished in the presence of Pd(OAc)2-Ph3P and ZnBr2. The stepwise twofold allylation of cycloalkanones leading to bridged ring systems uses 2-methylene-1,3-propylene diacetate. Allylation of active methylene compounds with allylic alcohols is promoted by triethylborane. ... 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

This reaction constitutes a special type of process in which a hydrogen atom and a nucleophile are added across the diene with fonnation of a carbon-hydrogen bond in the 1-position and a carbon-Nu bond in the 4-position. Some examples of such reactions are hydrosilylation [12-18], hydrostannation [19,20] amination [21,22], and addition of active methylene compounds [21 a,23,24], These reactions are initiated by an oxidative addition of H-Nu to the palladium(0) catalyst, which produces a palladium hydride species 1 where the nucleophile is coordinated to the metal (Scheme 8-1). The mechanism commonly accepted for these reactions involves insertion of the double bond into the palladium-hydride bond (hydride addition to the diene), which gives a (jr-allyl)palladium intermediate. Now depending on the nature of the nucleophile (Nu) the attack on the jr-allyl complex may occur either by external trans-aVtBck (path A) or via a cw-migration from palladium to carbon (path B). 

A difficulty sometimes encountered in the alkylation of active methylene compounds is the formation of unwanted dialkylated products. During the alkylation of the sodium salt of diethylmalonate, the monoalkyl derivative formed initially is in equilibrium with its anion. In ethanol solution, dialkylation does not take place to any appreciable extent because ethanol is sufficiently acidic to reduce the concentration of the anion of the alkyl derivative, but not that of the more acidic diethylmalonate itself, to a very low value. However, replacement of ethanol by an inert solvent favours dialkylation. Dialkylation also becomes a more serious problem with the more acidic cyanoacetic esters and in alkylations with very reactive electrophiles such as allyl or benzyl halides or sulfonates. 

Thiolsulphonates are effective in sulphenylation reactions, having been used recently for the stereoselective synthesis of allyl vinyl sulphides from RCH=CH-AlBu jBu". Mild reaction conditions are called for in the sulphenylation of active-methylene compounds by (ArS02)2CHSS02Ph. ... 

Treatment of either 1- (63) or 3-trimethylsilylallyl acetate (64) with nucleophiles (enamines or sodium derivatives of active methylene compounds) in the presence of a catalytic mixture of Pd(PPha)4 and triphenylphosphine gives vinylsilane derivatives, e.g. (65), exclusively. The E Z-ratio of the products is almost the same whichever allyl acetate is used, suggesting that the same intermediate tr-allylpalladium complex is involved in each case. 

Preparation of cyclopentanones by Pd-catalyzed intramolecular reaction of active methylene compounds with allylic ether moieties [34]. 

Typical nucleophiles known to react with coordinated alkenes are water, alcohols, carboxylic acids, ammonia, amines, enamines, and active methylene compounds 11.12]. The intramolecular version is particularly useful for syntheses of various heterocyclic compounds[l 3,14]. CO and aromatics also react with alkenes. The oxidation reactions of alkenes can be classified further based on these attacking species. Under certain conditions, especially in the presence of bases, the rr-alkene complex 4 is converted into the 7r-allylic complex 5. Various stoichiometric reactions of alkenes via 7r-allylic complex 5 are treated in Section 4. 

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... 

Various transition metals have been used in redox processes. For example, tandem sequences of cyclization have been initiated from malonate enolates by electron-transfer-induced oxidation with ferricenium ion Cp2pe+ (51) followed by cyclization and either radical or cationic termination (Scheme 41). ° Titanium, in the form of Cp2TiPh, has been used to initiate reductive radical cyclizations to give y- and 5-cyano esters in a 5- or 6-exo manner, respectively (Scheme 42). The Ti(III) reagent coordinates both to the C=0 and CN groups and cyclization proceeds irreversibly without formation of iminyl radical intermediates.The oxidation of benzylic and allylic alcohols in a two-phase system in the presence of r-butyl hydroperoxide, a copper catalyst, and a phase-transfer catalyst has been examined. The reactions were shown to proceed via a heterolytic mechanism however, the oxidations of related active methylene compounds (without the alcohol functionality) were determined to be free-radical processes. 

Allylation of nucleophiles. jr-Allyl palladium complexes (a) of a,/S-unsaturated epoxides react with active methylene compounds to give 1,4-adducts [allylic alcohols, equation (I)].10... 

Various cyclic compounds from three-membered rings to macrocycles have been prepared by intramolecular allylation. A typical example of this cyclization is the reaction of the monoacetate of 1,4-butenediol derivative 91 with the active methylene compound 92, which afforded the allylic alcohol 93. The three-membered chrysantemic acid derivatives 94 and 95 were then prepared after acetylation of 93, followed by Pd-catalysed intramolecular allylation [53],... 

Selenium dioxide (SeOi) oxidation Selenium dioxide is an excellent oxidizing agent for the oxidation of allylic and benzylic C-H fragments to allylic or benzylic alcohol. It also oxidizes the aldehydes and ketones to 1,2-dicarbonyl compounds (i.e. oxidation of active methylene groups to carbonyl groups). 

Koizumi and co-workers used optically active allylic chloroselenuranes bearing a 2-exo-hydroxyl-lO-bornyl group to produce optically active allylic selenium ylides in situ [52]. The nucleophilic reaction of the corresponding chiral chloro-selenurane and selenoxide with an active methylene compound occurs in a highly stereoselective manner to give the corresponding chiral selenium ylides with retention of configuration [53] (Scheme 33). 

With the introduction of the highly reactive allylic carbonates, coupling reactions can be carried out under neutral conditions. This is especially important when dealing with compounds that are sensitive to bases. The oxidative addition of allylic carbonates is followed by decarboxylation as the irreversible step to produce the 71-allylpal-ladium alkoxides. Since the alkoxides produced are rather poor nucleophiles, they do not compete with the carbon nucleophile for the 7i-allylpalladium complex but do deprotonate the active methylene compound. Attack of the Nu on the 7i-allylpalladi-um complex leads to the substitution product. 

On treatment with a palladium(O) catalyst, vinyl epoxides undergo facile unimolecular rearrangement to give dienols or enones depending on the substitution pattern of the substrate. In the presence of an active methylene compound in the reaction system, however, a single alkylation product is formed. Cyclic and acyclic vinyl epoxides participate equally well. The reaction proceeds with clean alkylation from the same face as the oxygen of the epoxide, and proceeds with allyl inversion (Scheme 22). ... 

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