Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of Enol Carbonates

• Published in: Journal of the American Chemical Society Vol. 131; no. 51; pp. 18343 - 18357
• Main Authors: Trost, Barry M, Xu, Jiayi, Schmidt, Thomas
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 30.12.2009; Amer Chemical Soc
• Subjects: Alkylation; Allyl Compounds - chemistry; Carbonates - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; Decarboxylation; Ketones - chemical synthesis; Palladium; Physical Sciences; Science & Technology; TRANSITION-METAL CATALYSIS; O-ACYLATION; SYNTHETIC REACTIONS; ALLYLATION; STEREOCHEMISTRY; ENANTIOSELECTIVE ALKYLATION; BOND FORMATION; ALPHA; LITHIUM; BETA-KETO CARBOXYLATES
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja9053948

Palladium-catalyzed decarboxylative asymmetric allylic alkylation (DAAA) of allyl enol carbonates as a highly chemo-, regio-, and enantioselective 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 disubstituted allyl groups. Our mechanistic studies reveal that, similar to the direct allylation of lithium enolates, the DAAA reaction proceeds through an “outer sphere” SN2 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.