Chiral Phosphoric Acid Catalyzed Diastereo- and Enantioselective Mannich-Type Reaction between Enamides and Thiazolones

An enantioselective Mannich-type reaction between enamides, serving as aliphatic imine equivalents, and thiazolones or an azlactone, serving as α-amino acid derived pronucleophiles, was investigated using a chiral phosphoric acid catalyst. By using thiazolones, Mannich adducts with a tetrasubstituted chiral carbon center at the α-position and an aliphatic substituent at the β-position were efficiently obtained with high diastereo- and enantioselectivities

Perfluorinated Aryls in the Design of Chiral Brønsted Acid Catalysts: Catalysis of Enantioselective [4 + 2] Cycloadditions and Ene Reactions of Imines with Alkenes by Chiral Mono-Phosphoric Acids with Perfluoroaryls

Perfluorinated aryl-incorporating chiral monophosphoric acids were used for highly stereoselective reactions of <i>N</i>-acyl and <i>N</i>-acyloxy aldimines with styrenes. Their electronic and steric profiles were established in comparison with those of phenyl, binaphthyl, and partially fluorinated aryls. The [4 + 2] cycloaddition reactions of <i>N</i>-benzoyl aldimines with alkenes proceeded with excellent diastereo- and enantioselectivities in the presence of the perfluorophenyl-incorporating chiral monophosphoric acid catalysts <b>1a</b> and <b>1c</b>. The stereoselective elaboration of polysubstituted cycloadducts to amines is described. The imino–ene reactions of <i>N</i>-Fmoc imines with alkenes have been successfully developed in a three-component manner. This process uses aldehydes, 9-fluorenylmethyl carbamate, and alkenes in the presence of a chiral monophosphoric acid catalyst, <b>2a</b>, possessing an F₁₀binaphthyl skeleton

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