Palladium-catalyzed decarboxylative asymmetric allylic alkylation (DAAA) of allyl enol carbonates as a highly chemo-, regio-and enantio-selective process for the synthesis of ketones bearing either a quaternary or a tertiary α-stereogenic center has been investigated in detail. Chiral ligand L4 was found to be optimal in the DAAA of a broad scope of cyclic and acyclic ketones including simple aliphatic ketones with more than one enolizable proton. The allyl moiety of the carbonates has been extended to a variety of cyclic or acyclic di-substituted allyl groups. Our mechanistic studies reveal that, similar to the direct allylation of lithium enolates, the DAAA reaction proceeds through an "outer sphere" S N 2 type of attack on the π-allylpalladium complex by the enolate. An important difference between the DAAA reaction and the direct allylation of lithium enolates is that in the DAAA reaction, the nucleophile and the electrophile were generated simultaneously. Since the π-allylpalladium cation must serve as the counterion for the enolate, the enolate probably exists as a tight-ion-pair. This largely prevents the common side reactions of enolates associated with the equilibrium between different enolates. The much milder reaction conditions as well as the much broader substrate scope also represent the advantages of the DAAA reaction over the direct allylation of preformed metal enolates.
The Pd-catalyzed reorganization of enol allyl carbonates to allylated ketones occurs asymmetrically in the presence of chiral ligands previously developed in this group. With 2-methylcyclohexanone, asymmetric regioselective alkylation occurs at the more substituted carbon without complications of polyalkylation. Alkylation to create quaternary centers in indanones and benzonabenone occurs in much higher ee than using tin or lithium enolates. The sense of enantioinduction in tetralones is opposite from the tin and lithium enolate examples. For the first time, asymmetric creation of tertiary centers occurs with high ee (78-99%). The different results between this reaction and the use of lithium or tin enolates suggest different mechanisms may be involved.
Excellent yields and enantioselectivities were achieved for the palladium‐catalyzed asymmetric allylic alkylation of vinylogous thioesters. The close‐to‐neutral reaction conditions ensure that this reaction can tolerate a wide range of functionalities. Furthermore, this approach provides a convenient protocol for the synthesis of synthetically important α,α‐ and γ,γ‐disubstituted cycloalkenones.
The first example of Pd-catalyzed asymmetric allyl alkylation of the conformationally nonrigid acyclic ketone enolates is reported with excellent yields, regioselectivity, and enantioselectivity. The double bond geometry of the allyl enol carbonates affects its reactivity, selectivity, as well as the absolute configuration of the products. An opposite enantioselectivity from what is predicted by a direct attack of the enolate on the allyl moiety of the pi-ally-Pd complex was observed. An alternative mechanism was proposed, which involves an inner sphere process of coordination of the enolate to Pd followed by reductive elimination.
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