Effect of the U-Shaped Cavity of Conformationally Flexible Chiral Lewis-Acidic Boron-Based Catalysts in Multiselective Diels-Alder Reactions.

The effect of the U-shaped cavity of conformationally flexible chiral Lewis acidic boron-based catalysts in multiselective Diels-Alder reactions was investigated. The U-shaped catalysts can recognize substituents at the terminal acetylene moiety of propynal based on steric factors and can also recognize alkyne and alkene substrates based on the match/mismatch between the catalysts and substrates. Moreover, even in a mixture of different catalysts and substrates, the desired competitive reactions can proceed multiselectively. This proof-of-concept study should contribute to the development of artificial enzyme-like catalysis in vitro.

Chiral Macrocyclic Catalysts for the Enantioselective Addition of Lithium Acetylides to Ketones.

Alkynyl addition to carbonyl compounds is a valuable synthetic method for the preparation of versatile chiral alcohols that are widely found in pharmaceuticals and natural products. Although a variety of enantioselective variations have been reported, alkynyl addition to simple ketones remains an unmet challenge due to their low reactivity and difficult enantiofacial discrimination. Here, we report a method for the catalytic enantioselective addition of lithium acetylide to a variety of ketones using macrocyclic lithium binaphtholates as catalysts. These reactions generally suffer from facile aggregation of lithium species, which leads to less active and selective catalysts. The macrocyclic structure designed in this study prevents such aggregation, affording a monomeric and highly active catalyst that can furnish enantioenriched tertiary alcohols from a variety of ketones within 5-30 min. Moreover, the confined cavity and lipophilicity of the macrocycle confer substrate specificity on the system, demonstrating a multiselectivity similar to that of enzymatic reactions. Thus, these findings offer new insights into the rational design of small-molecule artificial enzymes that exhibit high levels of reactivity and multiselectivity.

Multiselective Diels-Alder Reaction of α-Arylacroleins Catalyzed by Boron Tribromide-Assisted Chiral Phosphoric Acids.

A multiselective Diels-Alder (DA) reaction of α-arylacroleins with cyclopentadiene using BBr3-assisted chiral BINOL-derived phosphoric acid catalysts has been developed. This unusual exo- and enantioselective DA reaction can be multicontrolled by the chiral cavity of the in situ-formed acid-base cooperative catalysts, in particular, suppressing the competitive hetero Diels-Alder (HDA) reaction effectively.