Hydrogen Bonds-Enabled Design of a <i>C</i>₁‑Symmetric Chiral Brønsted Acid Catalyst

We have developed new <i>C</i>₁-symmetric, chiral bis-phosphoric acids with an electron-withdrawing group as one of the two substituents. This <i>C</i>₁-symmetric, chiral bis-phosphoric acid with a pentafluorophenyl group performs exceptionally well in the asymmetric Diels–Alder reaction of acrolein, methacrolein, and α-haloacroleins with substituted amidodienes. Control over the atropisomeric catalyst structure, enhancement of the catalytic activity, and differentiation of the asymmetric reaction space is possible by the remote control of the pentafluorophenyl group. Furthermore, we have conducted theoretical studies to clarify the roles of both intra- and intermolecular hydrogen bonds in the <i>C</i>₁-symmetric chiral environment of chiral bis-phosphoric acid catalysts. The developed strategy, <i>C</i>₁-symmetric catalyst design through hydrogen bonding, is potentially applicable to the development of other chiral Brønsted acid catalysts

Molecular Design of a Chiral Brønsted Acid with Two Different Acidic Sites: Regio‑, Diastereo‑, and Enantioselective Hetero-Diels–Alder Reaction of Azopyridine­carboxylate with Amidodienes Catalyzed by Chiral Carboxylic Acid–Monophosphoric Acid

A chiral Brønsted acid containing two different acidic sites, chiral carboxylic acid–monophosphoric acid <b>1a</b>, was designed to be a new and effective concept in catalytic asymmetric hetero-Diels–Alder reactions of azopyridine­carboxylate with amidodienes. The multipoint hydrogen-bonding interactions among the carboxylic acid, monophosphoric acid, azopyridine­carboxylate, and amidodiene achieved high catalytic and chiral efficiency, producing substituted 1,2,3,6-tetrahydro­pyridazines with excellent stereocontrol in a single step. This constitutes the first example of regio-, diastereo-, and enantioselective azo-hetero-Diels–Alder reactions by chiral Brønsted acid catalysis