Chemo-, Regio-, Diastereo-, and Enantioselective Palladium Allylic Alkylation of 1,3-Dioxaboroles as Synthetic Equivalents of α-Hydroxyketones

Abstract

We describe the development of a Pdcatalyzed asymmetric allylic alkylation (Pd-AAA) of acyclic α-hydroxyketones using boronic acids as traceless templates. Condensation of boronic acids with hydroxyketones generates 1,3-dioxaboroles, which can be used directly as pronucleophiles in Pd-AAA reactions. This strategy enables control of the enolate geometry, while removing the issue of O-alkylation. Allylic alcohols can be directly ionized in the presence of Pd(0) and chiral ligands to afford alkylation products with regio-and enantioselectivity. Additionally, a dynamic kinetic asymmetric transformation of allenyl electrophiles affords Calkylation products in high regio-, diastereo-, and enantioselectivity. To the best of our knowledge, this method represents the first example in Pd-AAA for setting point chirality on a nucleophile simultaneous to stereoinduction on an axial chiral allene.

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

“…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 A) . Recently, the Trost group has reported a unique strategy toward the asymmetric alkylation of benzoins via a 1,3‐dioxaborole intermediate (Scheme B) . 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, we hypothesized that preformation of a benzoin‐derived enolate precursor as a single geometric isomer would allow for an enantioselective alkylation process.…”

“…In 2008, the Glorius group reported the palladiumcatalyzed direct C-allylation of benzoins, as well as a tandem benzoin-allylation process. [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. 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. (Scheme 1C).…”

Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

“…Thus, racemic allenes 101 were transformed into enantioenriched allenols 103 using palladium catalysis and enantiopure phosphine ligands ( Scheme 22 , reaction c). 148 …”

A borane-mediated palladium-catalyzed reductive allylic alkylation of α,β-unsaturated carbonyl compounds

“…9 Additionally, a dual chiral catalytic rearrangement of allyl esters has been achieved using boron ester enolates and palladium catalysis. 10 Following our long standing interests in enantioselective Pd-AAA reactions (Scheme 1b), 11 we became interested in incorporating neutral enol boranes as pronucleophiles in transition metal catalysis, as a means of overcoming limitations imposed by decarboxylative AAA methods. 12 In particular, the formation of geometrically-controlled tetrasubstituted enol carbonates has remained challenging.…”