Allylic sources alkylation

The pi bond is the electron source. For allylic sources, the electron pair donor stabilizes the resultant cation. The simple alkene reactivity trend reflects the stabilization of the resultant carbocation by alkyl substitution and delocalization with other double bonds. The ranking of simple double bonds as electron sources basically is the more substituted, the more reactive. 

With anionic allylic sources, highly polar aprotic solvents increase the amount of lone pair alkylation because poor solvent stabilization of the anion leaves the heteroatom end less hindered by solvent. Conversely, groups bound to the heteroatom increase the steric hindrance about it, and therefore decrease the tendency toward heteroatom alkylation. For example, enamines (R2N-C=C) tend to alkylate on carbon rather than nitrogen (as shown in Section 8.4.5). 

In the following list are the extremes for the alkylation reaction of allylic sources however, product mixtures occur rather often. 

Storage Store in cool, dry place away from ignition sources keep tightly closed Uses Chem. intermediate in mfg. of pharmaceuticals, diuretics, barbiturates, hypnotics, varnishes, polymers, epichlorohydrin, epoxy resins, adhesives, plastics, glyceryol, insecticides synthesis of allyl compds. alkylating agent formerly as chem. intermediate for allyl starch Regulatory HAP SARA 313 reportable Calif. 

Allylic stannanes are an important class of compounds that undergo substitution reactions with alkyl radicals. The chain is propagated by elimination of the trialkyl -stannyl radical.315 The radical source must have some functional group that can be abstracted by trialkylstannyl radicals. In addition to halides, both thiono esters316 and selenides317 are reactive. 

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. 

Alkyl diazoacetates undergo little or no allylic C/H insertion when decomposed catalytically in the presence of appropriate olefins 6,13,I4). In contrast, such insertions occur with diazomalonates or ot-diazoketones. From the available facts, the conclusion can be drawn that different pathways may lead to what finally looks like the direct or rearranged allylic insertion product, but convincing evidence for one or the other mechanism is available only in a few cases. As Scheme 22 shows, the C/H insertion products 98-100 may arise from one of three major sources ... 

In contrast to the Johnson s D —> A-ring construction approach, Brown devised an A —> D-ring construction approach [22]. Starting from Wieland-Miescher ketone (30), a common source of the A, B-rings in the de novo synthesis of steroids, the C-ring was introduced via hydrazone allylation, ozonolysis, aldol condensation, and olefin isomerization (31 > 32). The D-ring was assembled by a reductive alkylation... 

AUylic alcohols constitute an alternative valuable source for the preparation of S-hydroperoxyalcohols suitable for peroxyacetalization to 1,2,4-trioxanes. A number of 3-alkyl-substituted allyl alcohols undergo a highly regio- and stereoselective ene-reaction with singlet oxygen to generate the corresponding /l-hydroperoxyalcohols. ... 

The chiral nonracemic bis-benzothiazine ligand 75 has been screened for activity in asymmetric Pd-catalyzed allylic alkylation reactions (Scheme 42) <20010L3321>. The test system chosen for this ligand was the reaction of 1,3-diphenylallyl acetate 301 with dimethyl malonate 302. A stochiometric amount of bis(trimethylsilyl)acetamide (BSA) and a catalytic amount of KOAc were added to the reaction mixture. A catalytic amount of chiral ligand 75 along with a variety of Pd-sources afforded up to 90% yield and 82% ee s of diester 303. Since both enantiomers of the chiral ligand are available, both R- and -configurations of the alkylation product 303 can be obtained. The best results in terms of yield and stereoselectivity were obtained in nonpolar solvents, such as benzene. The allylic alkylation of racemic cyclohexenyl acetate with dimethyl malonate was performed but with lower yields (up to 53%) and only modest enantioselectivity (60% ee). 

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. 

Trimethylsilyl alkyl and aryl sulfides were found to function as latent sources of a sulfide nucleophile when used in conjunction with allyl carbonates or vinyl epoxides with Pd catalysts (equation 64).223... 

A unique feature of the transition-metal-catalyzed allylic alkylation is its ability to convert starting materials of various symmetry types, such as racemic, meso- and achiral compounds, into optically pure material, Strategies to effect such transformations derive from recognition of the stereochemical courses in each step of the catalytic cycle and analysis of symmetry elements in the substrate or intermediate. Figure 8E.1 summarizes potential sources of enantio-discrimination in transition-metal-catalyzed allylic alkylation. 

Although metal-olefin complexation can be a source of enandoselection, reactions exploiting this mechanistic motif have not been developed much. Due to the facile enantioface interconversion process, the origin of the enantioselection often reverts back to Type C alkylation (Figure 8E, 1). To transfer chiral recognition of the coordination process to the ee of the product, kinetic trapping of the incipient 7t-allyl complex is required prior to any isomerization process. For this reason, few successful examples have come from the use of more reactive heteroatom nucleophiles (N, O and S) and/or intramolecular reactions. 

When the alkylation was performed with ethyl allyl carbonate as the precursor of the it-allyl intermediate, only 32% ee was obtained, indicative of a subtle proton-transfer process involved in the catalytic process such as in Scheme 8E.39. The chiral rhodium catalyst was shown to be the primary source of the asymmetric induction because the same reaction in the absence of the rhodium catalyst generated a racemic product in 91% yield. It is interesting that the use of only half an equivalent of the chiral ligand together with half an equivalent of achiral ligand (dppb) with respect to [Pd + Rh] was sufficient to give a high enantioselectivity (93% ee). 

The conversion of halides into azides has been reviewed recently197-199 and the reader is directed to these sources for further detail. In general, alkyl and allylic halides are readily... 

Addition of an electrophile (see Electrophile) to metal-bound cyanides will often form an isocyanide ligand (see Electrophile), -CsN-R. For example, the compound [Fe P(OMe)3 (NO)2(j7 -C3H4R)], which is a source of the allyl cation ( -C3H4R)+, reacts with trans-[Mn(CN)(CO)(dppm)2] to alkylate the cyanide, giving an allyl isocyanide ligand (equation 8). The tungsten alkyne... 

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. ... 

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