Catalytic Enantioselective Carbonyl Propargylation Beyond Preformed Carbanions: Reductive Coupling and Hydrogen Auto‐Transfer

Abstract

Graphical Abstract Chiral metal complexes catalyze enantioselective carbonyl propargylation via reductive coupling or as hydrogen auto-transfer processes, in which reactant alcohols serve dually as reductant and carbonyl proelectrophile. Unlike classical propargylation protocols, which rely on allenylmetal reagents or metallic reductants (e.g. NHK reactions), reductive protocols for carbonyl propargylation can occur in the absence of stoichiometric metals, precluding generation of metallic byproducts. Propargylations of this type exploit both enyne and propargyl halide pronucleophiles.

Preise der American Chemical Society 2020

“…Krisches Gruppe ist führend auf dem Gebiet reduktiver C‐C‐Kupplungen mit π‐ungesättigten Substraten. In einer Angewandte‐Chemie ‐Zuschrift stellten sie eine enantioselektive Allylierung von Inonen vor, und sie steuerten einen Minireview über enantioselektive Carbonylpropargylierungen zum “10th Anniversary Issue of ChemCatChem ” bei. Krische ist Mitglied des internationalen Beirats von ChemCatChem .…”

American Chemical Society National Awards 2020

“…Krische's group has pioneered reductive C−C couplings with abundant π‐unsaturated feedstocks. In a Communication in Angewandte Chemie , they presented an enantioselective allylation of acetylenic ketones, and they contributed a Minireview on enantioselective carbonyl propargylation to the 10th Anniversary Issue of ChemCatChem . Krische is on the International Advisory Board of ChemCatChem .…”

Enantioselective Iridium‐Catalyzed Allylation of Acetylenic Ketones via 2‐Propanol‐Mediated Reductive Coupling of Allyl Acetate: C14‐C23 of Pladienolide D

“…To address these limitations, we have developed metal‐catalyzed carbonyl reductive couplings that utilize elemental hydrogen, 2‐propanol or formate as terminal reductant, as well as related hydrogen auto‐transfer processes wherein alcohols serve as hydrogen donor and carbonyl proelectrophile . While this technology has enabled diverse catalytic enantioselective aldehyde allylations and propargylations, asymmetric transfer hydrogenative allylations of ketones are restricted to vicinal dicarbonyl compounds…”