Iridium‐Catalyzed Diastereoselective and Enantioselective Allylic Substitutions with Acyclic α‐Alkoxy Ketones

Abstract

The asymmetric alkylation of acyclic ketones is a longstanding challenge in organic synthesis. We report diastereoselective and enantioselective allylic substitutions with acyclic α-alkoxy ketones catalyzed by a metallacyclic iridium complex to form products with contiguous stereogenic centers derived from the nucleophile and electrophile. These reactions occur between allyl methyl carbonates and unstabilized copper(I) enolates generated in situ from acyclic α-alkoxy ketones. The resulting products can be readily converted to enantioenriched tertiary alcohols and tetrahydrofuran derivatives without erosion of enantiomeric purity.

Catalytic Enantioselective and Diastereoselective Allylic Alkylation with Fluoroenolates: Efficient Access to C3‐Fluorinated and All‐Carbon Quaternary Oxindoles

“…[9] Although many examples of allylic alkylations producing a single chiral center with high asymmetric induction are known, the stereocontrolled formation of two adjacent chirality centers continues to be a challenge. [10] …”

Iridium-Catalyzed Diastereo-, Enantio-, and Regioselective Allylic Alkylation with Prochiral Enolates

“…10 In these reactions, the geometry of the acyclic enolate, formed by deprotonation with the lithium base, is controlled by chelation to a copper(I) cation. Interestingly, the identity of the cation associated with the base was also found to play an integral role in achieving high diastereoselectivities, with KHMDS providing much lower selectivities than LiHMDS.…”

Palladium‐Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Protected Benzoin‐Derived Enol Carbonates

“…[4] However, the direct synthesis of a fullysubstituted α-carbonyl stereocenter in an enantioselective manner has only recently been developed. [6] Recently, the Trost group has reported a unique strategy toward the asymmetric alkylation of benzoins via a 1,3dioxaborole intermediate (Scheme 1B). [5] They note, however, that performing the transformation in an asymmetric fashion proved to be challenging, likely due to nonselective formation of a mixture of enolates.…”

“…Several years later, the Hartwig group reported the use of iridium-catalysis for the diastereo-and enantioselective synthesis of branched α-alkoxy ketones via a stereodefined enolate, formed by enolization in the presence of a copper additive (Scheme 1A). [6] Recently, the Trost group has reported a unique strategy toward the asymmetric alkylation of benzoins via a 1,3dioxaborole intermediate (Scheme 1B). [7] Due to the importance of this structural motif, and in continuation of recent research from our group regarding the synthesis and utility of fully-substituted acyclic enolates for palladium-catalyzed allylic alkylation, [8] we hypothesized that preformation of a benzoin-derived enolate precursor as a single geometric isomer would allow for an enantioselective alkylation process.…”