Merging Chiral Brønsted Acid/Base Catalysis: An Enantioselective [4 + 2] Cycloaddition of o-Hydroxystyrenes with Azlactones

Abstract

An enantioselective [4 + 2] cycloaddition of o-hydroxylstyrenes with azlactones has been established by merging chiral Brønsted acid (chiral phosphoric acid) and base (chiral guanidine) catalysis, which constructed a biologically important dihydrocoumarin scaffold in an efficient and enantioselective style (up to 99% yield, 96:4 er). This approach has not only realized the successful application of o-hydroxylstyrenes as oxa-diene precursors in catalytic asymmetric cycloadditions but also established a new cooperative catalytic system of chiral phosphoric acid and chiral guanidine.

Aromatizative Inverse‐Electron‐Demand Hetero‐Diels‐Alder Reaction in the Synthesis of Benzothiophene Derivatives

“…presented the first asymmetric IEDDA reaction of azlactones catalyzed by chiral phosphoric acid . Subsequently, various electron‐poor heterodienes were employed in this reaction including chalcones, β,γ‐unsaturated‐α‐keto esters, o ‐hydroxystyrenes or quinone methides and other systems…”

First example of an organocatalytic asymmetric Mannich reaction between aldimines of glycinates and sulphonyl imines

“…40,41 Therefore, chiral guanidine (6a) was synthesized and used as catalyst for this Mannich-type reaction. The result revealed that this catalyst could catalyze the reaction with high yield and poor stereoselectivity (Table 1, entry 6).…”

Catalytic Asymmetric Intramolecular [4+2] Cycloaddition of In Situ Generated ortho‐Quinone Methides

“…The challenges of applying o ‐QMs in asymmetric [4+2] cycloadditions are associated not only with their transient nature, but also with their weak and ill‐defined interactions with enantiopure catalysts. Existing methods rely either on simultaneously activating both the o ‐QM and its reaction partner or on the exclusive activation of o ‐QMs towards cycloadditions with styrenes …”