Allylic sources esters

Allylic sources attack carboxyl derivatives such as esters almost exclusively on carbon by the path AdN, then Ep. As in Section 8.5.5, the enolate source should be the deprotonated sink or the sink should not be enolizable. A final proton transfer to give a resonance delocalized stable anion is frequently the driving force for the reaction. 

The basic media exceptions can be easily understood if we invoke HSAB theory and realize that the kinetic and thermodynamic products are different. As L becomes a poorer donor, the partial plus on the acyl carbon increases, making it harder. Acylation on the heteroatom of the allylic source is fast for acyl halides and anhydrides where the acyl carbon is harder (greater partial plus) than the acyl carbon of esters. If the reaction is under kinetic control (allylic source added to an excess of acyl halide or anhydride), the Z-acylated product is formed however, if equilibration occurs (excess of allylic source), the product will be the C-acylated, thermodynamic product. 

The ester enolate is an allylic source that can serve as a base or a nucleophile. The original ester has acidic hydrogens within range of the enolate. The ester carbonyl is an electrophilic sink (a polarized multiple bond with attached leaving group). 

The enzyme catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid catalyzed dimerization of alkenes discussed m Section 6 21 The reaction of an allylic pyrophosphate or a carbo cation with a source of rr electrons is a recurring theme m terpene biosynthesis and is invoked to explain the origin of more complicated structural types Consider for exam pie the formation of cyclic monoterpenes Neryl pyrophosphate formed by an enzyme catalyzed isomerization of the E double bond m geranyl pyrophosphate has the proper geometry to form a six membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit... 

Scheme 10.17 illustrates allylation by reaction of radical intermediates with allyl stannanes. The first entry uses a carbohydrate-derived xanthate as the radical source. The addition in this case is highly stereoselective because the shape of the bicyclic ring system provides a steric bias. In Entry 2, a primary phenylthiocar-bonate ester is used as the radical source. In Entry 3, the allyl group is introduced at a rather congested carbon. The reaction is completely stereoselective, presumably because of steric features of the tricyclic system. In Entry 4, a primary selenide serves as the radical source. Entry 5 involves a tandem alkylation-allylation with triethylboron generating the ethyl radical that initiates the reaction. This reaction was done in the presence of a Lewis acid, but lanthanide salts also give good results. 

The radical source must have some functional group X that can be abstracted by trialkylstannyl radicals. In addition to halides, both thiono esters and selenides are reactive. Allyl tris(trimethylsilyl)silane can also react similarly.232 Scheme 10.11 illustrates allylation by reaction of radical intermediates with allylstannanes. 

Esters of allylic alcohols with resin-bound carboxylic acids can be converted into allyl palladium complexes, which react with carbon nucleophiles and with hydride sources to yield the formally reduced allyl derivatives (Entries 3 and 4, Table 3.47). Alkyl sulfonates have been reduced to alkanes with NaBH4 (Entry 5, Table 3.47). Aryl sulfonates (Entry 6, Table 3.47) and aryl perfluoroalkylsulfonates [814] can be reduced to alkanes by treatment with catalytic amounts of Pd(II) and formic acid as a hydride source. 

One of the amenities of present-day organic synthesis is the availability of intermediates from the many chemical supply companies. More than 100 allylic alcohols (excluding extensive listings of phorbol esters and prostaglandin structures) are offered for sale from these sources. Two concerns about such supplies should be noted. The first is the EZZ composition of acyclic allylic alcohols, which should be checked when it is not specified, and second is the optical purity of allylic alcohols offered in optically active form, which likewise should be checked. 

Heathcook et al. have performed a diastereoselective aza-ene reaction using chiral di-(+)-menthyl diazenedicarboxylate 91 as the nitrogen source [54]. Compound 91 was found to react with various alkenes in the presence of 2 equiv. SnCl4, and the corresponding allylic aminated product was obtained in good yield and with de up to 42 %. The problem with this approach was the removal of the chiral menthyl ester auxiliary, which was found to be rather difficult. 

Bennett has shown that sugar-derived substrates can also be used for the preparation of highly functionalised cyclopentanes.82,83 For example, treatment of iodide 75 with Sml2 initiated a highly diastereoselective construction of cyclopentane 76 (Scheme 5.50). These reactions require the presence of HMPA and a proton source to avoid competing 1,4-reduction of the a,p-unsaturated ester and cleavage of the allylic C-O bond.82,83... 

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. ... 

Tetracarbonylnickel is an inexpensive (although toxic) source of Ni° and its use for the in situ generation of allylnickel intermediates dates back at least 25 years. In fact, the nickel allylation/methoxycarbo-nylation of alkynes with allyl chloride and an excess of Ni(CO)4 in methanol has b n reviewed (Scheme 15). Accordbgly, dienoates (68) (35-80%) were obtained in a regio- and stereo-selective manner corresponding to a metallo-ene cis addition of an allylnickel compound at the less-substituted termirud C-1 of (67), followed by a CO insertion into the resulting vinylnickel species. The dienyl esters (68) were accompanied by variable amounts of cyclopentenones, indicating the possibility of consecutive CO insertion processes. 

Bisalkoxycarbonylcarbenes have been generated from several different sources. In the photochemical reaction of diazomalonic esters, the adducts to alkenes have been obtained with substantial retention of stereochemistry when the singlet species is allowed to react. On the other hand, an almost complete loss of olefin stereochemistry is observed in the reaction of triplet species Under the catalytic conditions, the cyclopropanation occurs stereospecifically. The major side reactions in these cyclopropanations are allylic C-H... 

Additives (cosolvents) which serve as ligands have great influence on the reducing power of Smlj. Allylic and propargylic derivatives are reduced via it-allylpalladium species, and the proton source has important effects on the generation of allenes or alkynes. Chiral allenic esters are obtained when pantolactone delivers a proton to racemic organosamarium species derived from 4-phosphato-2-alkynoic esters. ... 

The research group of Muzart and Henin studied extensively the palladium-catalyzed EDP of allyl- or benzyl-carboxylated compounds. Mainly two types of substrates, prochiral enol carbonates A and racemic (3-keto esters B, were used to afford enols C as transient species [25]. In the presence of a chiral proton source, asymmetric protonation/tautomerization of enols led to enantioenriched ketones D... 

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