Palladium-Catalyzed Asymmetric Allylic α-Alkylation of Acyclic Ketones

Abstract

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.

Metal catalyzed allylic alkylation: its development in the Trost laboratories

“…Acyclic substrates work equally well. 69,70 Enolate geometry controls facial selectivity as shown in eq 68 and 69 wherein switching from a Z to an E enolate inverts the stereochemistry of the newly formed stereocenter. No enolate equilibration occurs nor does any polyalkylation.…”

Transition metals in organic synthesis: Highlights for the year 2005

“…(68)) [611]. (68) Palladium catalyzed enantioselective allylic alkylation of allyl-enol carbonates derived from ketones [612,613]. A palladium-catalyzed asymmetric alkylation of 3-aryloxindoles with allyl acetate was developed [614].…”

Preparation of (S)-2-Allyl-2-Methylcyclohexanone

“…To highlight the previous deficiency in the literature, 2-allyl-2-methylcyclohexanone had not been prepared in high enantiomeric excess prior to our work since few alternative synthetic methods are available 20. Related enantioselective transformations for the conversion of allyl enol carbonates and silyl enol ethers to α-quaternary cycloalkanones, also based on earlier work by Tsuji,21 have been developed by our group6 and others 22. However, β-ketoester substrates are often preferable due to the ease of synthesis and ease of substrate handling.…”