Cooperative Palladium/Brønsted Acid Catalysis toward the Highly Enantioselective Allenylation of β-Keto Esters

Abstract

We report the first enantioselective allenylation of Pd enolates enabled by cooperative Pd/Brønsted acid catalysis employing β-keto esters and propargyl alcohols. The enantioselectivity originates solely from an in-situ-generated chiral metal enolate in an open transition state with no additional binding of the propargyl component to the catalyst. Thus a broad substrate scope was established, furnishing hitherto inaccessible products in very good yields with excellent enantioselectivities (up to >99:1 e.r.).

Enantioselective 1,6-Addition of β-Ketoester Enolates to In Situ Generated para-Quinone Methides Enabled by Cooperative Palladium and Brønsted Acid Catalysis

“…Our approach was based on the cooperative catalytic activity involving the generation of p -QM by a Brønsted acid released by the Pd–aqua complex in solution and the Brønsted base activation of the β-ketoester by the active palladium species. This type of reaction design has been demonstrated by our group in a number of examples, particularly with o -quinone methides …”

Divergent Cyclizative Approaches of In Situ Formed β-Keto-Allenes: Chemo- and Regioselective Synthesis of Bicyclic Furans, and Pyrroles

“…Experimental procedures and characterization data for all reactions and products, including copies of copies of 1 H and 13 C{H} NMR spectra and details of singlecrystal data of compounds 4d, 6d, 8o, and 9b (CCDC 2221161, 2232799, 2217645, and…”

“…Sun and co-workers developed axially chiral allenes from tert -propargyl alcohols and α-acyl cyclic ketones by treating them with chiral phosphoric acids . Another strategy by employing β-keto esters and propargyl alcohols using cooperative Pd/chiral Brønsted acid catalysis is reported by Schnider et al this year . Though elegant approaches are developed by employing these two substrates, the cyclization reactions of these substrates were not studied for the formation of corresponding bicyclic compounds.…”

Recent advances in the metal-catalyzed asymmetric synthesis of chiral allenes

“…36 A decent scope of substrates were readily tolerated, affording the corresponding chiral allenes 135 and recovered propargyl alco- Cooperative Pd/Brønsted acid catalyzed enantioselective allenylation of β-keto esters was recently demonstrated by Schneider's group (Scheme 22). 37 The palladium catalyst complexed with β-keto esters to form chiral enolate 145. Meanwhile, dehydration of propargyl alcohol assisted by Brønsted acid HSbF 6 generated from chiral C4 produced carbocation 144.…”