Lithium and magnesium enolates of cyclohexanone undergo palladium-catalyzed allylic alkylations under mild conditions. Diastereoselectivity and enantioselectivity are observed when the diphenyland dimethyl-substituted allylic substrates 1a and 1b are reacted with cyclohexanone or ethyl mesityl ketone. The lithium enolates of cyclohexanone, cyclopentanone and a-tetralone lead to the alkylations products 12-14 in an enantioselective manner. Axially chiral biphenyl-and binaphthyl-bisphosphanes provide high enantioselectivity and/or diastereoselectivity. In the case of the lithium enolates, the presence of lithium chloride is also crucial to reactivity and stereoselectivity. The stereochemical outcome of the allylic alkylation of cyclohexanone and acetophenone has been investigated by the palladium-catalyzed reaction of their lithium enolates with the cis/ trans isomeric alkenes (Z)-18 and (E)-19. It turns out that the preformed, non-stabilized enolates attack pallyl-palladium complexes generated in situ from the face opposite to the noble metal thus following the stereochemical pathway of soft, stabilized carbanions.
The Tsuji-Trost protocol has been successfully employed for the allylic alkylation of preformed lactone enolates. It has been demonstrated that this Pd-catalyzed reaction can be carried out in an enantio- and diastereoselective manner. The use of additives, such as LiCl, was found to be crucial for reaching high levels of product selectivity. For one particular pair of reactants, density functional theory was used to investigate the mechanism of the nucleophilic addition. Among the five pathways considered, the reaction between an (allyl)Pd(BINAP) complex and a LiCl-lithium enolate adduct is predicted to be the most likely route for C-C bond formation. LiCl plays a key role as the connecting link between the noble metal and the enolate in the kinetically favored transition state. The computed diastereoselectivity ratio is in good agreement with the experimentally observed value.
Doubly deprotonated carboxylic acids undergo smooth palladium-catalyzed carbon alkylations with the allylic substrates methyl allyl carbonate and (E)-methyl (pent-3-en-2-yl) carbonate to give g,d-unsaturated carboxylic acids. A diastereoselective and enantioselective protocol leads to (2S,3R)-hexenoic acid in 87% ee.
In an enolate Claisen rearrangement, deprotonated allyl phenylacetate undergoes a smooth conversion at -78°C to 2-phenyl-4-pentenoic acid under palladium(0) catalysis. By using labelled starting materials in crossover experiments,
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