Organocatalytic Access to Enantioenriched Dihydropyran Phosphonates via an Inverse-Electron-Demand Hetero-Diels–Alder Reaction

Abstract

The enantioselective inverse-electron-demand hetero-Diels-Alder reaction of the remote olefin functionality in dienamines has been developed by the simultaneous activation of α,β-unsaturated aldehydes and acyl phosphonates. The dual activation is based on an organocatalyst that activates both the α,β-unsaturated aldehyde, through dienamine formation, and the acyl phosphonate by hydrogen-bonding. The enantioselective reaction results in the formation of dihydropyran frameworks with three contiguous stereogenic centers. Different substitution patterns are possible for both the heterodiene and the dienophile, and the target products are obtained in good yields and up to 92% ee. The potential of the reaction is demonstrated by transformation of the products into valuable and complex synthons.

Old tricks, new dogs: organocatalytic dienamine activation of α,β-unsaturated aldehydes

“…In an associated study, the same group developed the synthesis of enantioenriched dihydropyran phosphonates ( 137 ) 53 using acyl phosphonates ( 136 ) instead of the 1,2-dicarbonyl compounds ( 134 ) (compare Schemes 37 and 38 ). In this case, the products were also obtained with good ee values and yields, allowing even the use of alkyl acyl phosphonate derivatives.…”

Organocatalytic Strategies for the Development of the Enantioselective Inverse‐electron‐demand Hetero‐Diels‐Alder Reaction

“…Furthermore, it is also worth to mention that the reaction displays the usual β,γ-regioselectivity (Scheme 22). [36] Two years later, Pericàs and coworkers reported the asymmetric synthesis of tetrahydropyranopyrazole derivatives through a bifunctional-organocatalyzed inverse-electron-de- mand oxa-Diels-Alder reaction. The reaction takes place in the presence of differently substituted enals and alkylidene pyrazolones with excellent results (Scheme 23).…”

“…Furthermore, it is also worth to mention that the reaction displays the usual β , γ ‐regioselectivity (Scheme 22 ). [36] …”

Polymeric p–n Nanojunctions: Formation and Electrochemical Properties of C60‐Pd@Polypyrrole Core–Shell Nanoparticles

“…A closely related inverse electron demand hetero‐Diels–Alder reaction of α,β‐unsaturated aldehydes 141 with α,β‐unsaturated acyl phosphonates 149a catalyzed by the same squaramide‐based aminocatalyst XXIII also proceeded through the dienamine intermediate (Scheme ) 76. This transformation resulted in various dihydropyran derivatives 150 (after reduction of the aldehyde functionality) with three contiguous stereogenic centers from various heterodienes and dienophiles bearing different substituents in good yields, good to excellent dr and good ee .…”