Cyclic allylic acetates, alkylation

TABLE 8E.6. Alkylation of Cyclic Allylic Acetates with Malonates... 

Cyano compounds liquid crystals, 12, 278 in silver(III) complexes, 2, 241 Cyanocuprates, with copper, 2, 186 Cyano derivatives, a-arylation, 1, 361 Cyanosilanes, applications, 9, 322 Cyclic acetals, and Grignard reagent reactivity, 9, 53 Cyclic alkenes, asymmetric hydrosilylation, 10, 830 Cyclic alkynes, strained, with platinum, 8, 644 Cyclic allyl boronates, preparation, 9, 196 Cyclic allylic esters, alkylation, 11, 91 Cyclic amides, ring-opening polymerization, via lanthanide catalysis, 4, 145... 

Cyclopropane formation was also observed as a side reaction (1 9 up to 1 1) in the palladium-catalyzed coupling of ketene alkyl silyl acetals with open-chain and cyclic allyl acetates. The reaction is interpreted as proceeding via nucleophilic central attack of a jr-allyl intermediate. Although cyclopropane formation proceeds only with low yields, a highly stereospecific pathway was observed with substituted 3-cyclohexenyl acetates. ... 

Alkylation of sodium 1-(alkoxycarbonyl)methyIphosphonates proceeds equally with acetates in THF from low to room temperature or in DME at reflux. The asymmetric allylic alkylation of the sodium diethyl l-(ethoxycarbonyl)methylphosphonate with 3-acetoxy-l,3-diphenyl-l-propene and cyclic allylic acetates in the presence of a chiral palladium catalyst, prepared from chiral phosphine and palladium acetate, in THF at room temperature proceeds in good yields (44-88%) and high ec s. ... 

Hard nucleophiles also react with cyclic allylic acetates and halides. For example, cyclohexenyl acetate reacts with a vinylmagnesium species in the presence of PROLIPHOS to give the product of allylic alkylation in 30% ee [108]. 

Table 4. Diastereoselective Alkylation of Cyclic Allyl Acetates Proceeding via a /ncso-7r-Allylpalladium Intermediate...

Table 5. Chemoselectivity with Palladium-Promoted Alkylation of Functionalized Cyclic Allyl Acetates with Soft Carbanions...

Hou, Dai and co-workers reported a related oxazoline ligand that contains a pendant binaphtholate group that catalyzes the selective formation of branched allylic amines and allylic alkylation products from linear or brandied allylic esters. Helmchen developed the phosphine ligand with a pendant carboxylic acid that is particularly enantioselective for the reactions of aliphatic cyclic allylic acetates. "... 

The new binaphthyl ligands 49 [22] and 50 [23] have led to a breakthrough in the copper catalyzed 1,4-addition of organozinc reagents to a,jff-unsatu-rated ketones, a reaction which has proved to be difficult if carried out enantioselectively. Selectivities up to 96 % ee have been reached with cyclic substrates, while acyclic substrates still leave room for further improvement. 50 has also been successfully employed in palladium-catalyzed alkylations of allyl acetates [24]. 

The transition metal-catalyzed allylation of carbon nucleophiles was a widely used method until Grieco and Pearson discovered LPDE-mediated allylic substitutions in 1992. Grieco investigated substitution reactions of cyclic allyl alcohols with silyl ketene acetals such as Si-1 by use of LPDE solution [95]. The concentration of LPDE seems to be important. For example, the use of 2.0 M LPDE resulted in formation of silyl ether 88 with 86 and 87 in the ratio 2 6.4 1. In contrast, 3.0 m LPDE afforded an excellent yield (90 %) of 86 and 87 (5.8 1), and the less hindered side of the allylic unit is alkylated regioselectively. It is of interest to note that this chemistry is also applicable to cyclopropyl carbinol 89 (Sch. 44). 

Enolates of cyclic 1,3-diketones, such as 2-methyl-1,3-cyclopentanedione and 2-methyl-1,3-cyclohex-anedione, are especially prone to 0-alkylation because of their W geometry and steric hindrance at carbon. However, C-alkylations of these species can be conducted reasonably successfully in protic solvents, e.g. water.280 Trost and Curran have reported high yields for the C-alkylation of cyclic 1,3-diketones with allylic acetates in the presence of palladiumfO) catalysts and DBU (Scheme 80). 

H elimination from allylic complexes leads to 1,3-dienes and this is the final step of some synthetically useful reactions such as the Pd-catalyzed elimination of acetic acid from allylic acetates to give l,3.dienes. The fi-U elimination is believed to be analogous to that in the alkyl complexes, by previous isomerization of the allyl moiety from to a. However, recently some studies suggest that alternative mechanisms can be operating, sometimes simultaneously, such as direct deprotonation of the H in /i position to the allyl group [90-92], or even, in some special cases, a cyclic mechanism outside the metal coordination sphere... 

Interception of the Tr-allyl palladium complex by soft nucleophiles, particularly malonates, has been described above. Alkenes, alkynes and carbon monoxide can also insert into the Tr-allyl palladium complex, generating a u-alkyl palladium species. When an internal alkene is involved, a useful cycbzation reaction takes place (sometimes called a palladium-ene reaction).Addition of palladium(O) to the allylic acetate 225 gave the cyclic product 226 (1.225). The reaction proceeds via the -ir-allyl palladium complex (formed with inversion of configuration), followed by insertion of the alkene cis- to the palladium and p-hydride elimination. In some cases it is possible to trap the a-alkyl palladium species with, for example, carbon monoxide. 

The allylation of cyclic acetates such as cyclopentenyl or cyclo-hexenyl and cycloheptenyl derivatives also has been widely studied. For exart ile, the allyl palladium chloride dimer (1) is a useful catalyst precursor in the kinetic resolution of 2-cyclohexenyl acetate using Trost s chiral ligands pockets in conjunction to the planar chirality of ferrocene (eq 46). 1 The conversion was stopped at 54%, which allowed high enantiomeric excess for both the alkylated derivative and the chiral allylic acetate. 

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

Asymmetric nickel-catalyzed allylic alkylation with soft carbon-centered nucleophiles was reported in 1996 by Mortreux and his co-workers. Use of a catalytic amount of [Ni(cod)2] together with chiral diphosphines 138 promotes the allylic alkylation of a cyclic ester such as 2-cyclohexenyl acetate with dimethyl malonate in the presence of BSA and gives the corresponding alkylated compounds only with a moderate enantioselectivity (40% ee) (Equation (42)). 

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