Deconjugated‐Ketone‐Derived Dienolates in Remote, Stereocontrolled, Aromative aza‐Diels‐Alder Cycloaddition

Abstract

In the manuscript, the application of β,γ‐unsaturated ketones as precursors of electron‐rich dienophiles in the organocatalytic, aromative inverse‐electron‐demand hetero‐Diels‐Alder cycloaddition is described. The reaction leads to the formation of biologically relevant benzofuran derivatives bearing additional tetrahydropyridine ring. The reaction is fully site‐selective and occurs preferentially at the distal double bond of the dienolate intermediate. Given the absolute configuration assignment a step‐wise mechanism has been proposed and the formation of aromatic benzofuran ring indicated as the driving force of the cascade.magnified image

Cinchona Derivatives as Bifunctional H‐bonding Organocatalysts in Asymmetric Vinylogous Conjugate Addition Reactions

“…reported an interesting application of allyl ketones in asymmetric inverse‐electron‐demand hetero‐Diels‐Alder type annulation reaction (Scheme 21). [35d] Cinchonidine‐derived thiourea C9 catalyzed the regioselective asymmetric cascade between β,γ‐unsaturated ketones 49 and unsaturated imine 48 . The authors rationalized that the aromatization of the benzofuran ring could be the driving force for this transformation and proposed a step‐wise vinylogous Michael‐aza‐Michael mechanism to explain the product formation.…”

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

“…It is also worth to mention that a β,γ-regioselectivity is reported as a consequence of the most nucleophilic γ-position of the in situ formed dienolate. [43] Another recent example has been released by Zu and coworkers. In this report, the enantioselective synthesis of 3,4'pyranyl spirooxindole derivatives with three contiguous chiral centers in their structure were achieved via deprotonation of β,γ-unsaturated α-keto esters (Scheme 29).…”

“…In this example, the authors claim that the reaction takes place via a stepwise mechanism. It is also worth to mention that a β , γ ‐regioselectivity is reported as a consequence of the most nucleophilic γ ‐position of the in situ formed dienolate [43] …”

“…It is also worth to mention that a β , γ ‐regioselectivity is reported as a consequence of the most nucleophilic γ ‐position of the in situ formed dienolate. [43] …”

Enantioselective Inverse-Electron Demand Aza-Diels–Alder Reaction: ipso,α-Selectivity of Silyl Dienol Ethers

“… 11 Nevertheless, all of these examples show how the reaction takes place through the β,γ-alkene of the in situ generated dienolate (1,5-reactivity, Scheme 1 A). 9 − 11 …”