Bifunctional Thiourea-Catalyzed Asymmetric Inverse-Electron-Demand Diels–Alder Reaction of Allyl Ketones and Vinyl 1,2-Diketones via Dienolate Intermediate

Abstract

Inverse-electron-demand Diels−Alder reactions have attracted intense research focus. However, enolate and enamine are the most employed intermediates to realize such transformation, and the use of dienolate intermediate remains elusive. Reported herein is the asymmetric inverse-electron-demand oxa-Diels−Alder reaction between allyl ketones and alkenyl 1,2-diketones using a bifunctional thiourea catalyst. The reaction afforded various highly functionalized dihydropyrans with good to excellent enantioselectivities under mild conditions, and further novel transformations on the products have also been realized.

Organocatalytic Remote Asymmetric Inverse‐Electron‐Demand Oxa‐Diels‐Alder Reaction of Allyl Ketones with Isatin‐Derived Unsaturated Keto Esters

“…The isatin‐derived β , γ ‐unsaturated α ‐keto esters 1 a – 1 n were prepared according to the reported literature procedures [5] . The allyl ketones 2 a – 2 h , 2 j and 2 k were prepared according to the reported literature procedures [15,20] …”

“…[5] The allyl ketones 2 a-2 h, 2 j and 2 k were prepared according to the reported literature procedures. [15,20]…”

“…Recently, the allyl ketones which widely applied to α-or γ-selective Michael additions or aldol reactions, [14] have been successfully utilized in a remote asymmetric inverse-electrondemand (IED) oxa-Diels À Alder reaction for construction of pyran skeletons. [15] Nowadays, the development of asymmetric remote activation via organocatalysis is still a challenging research topic in the area of organic synthesis because of the long distance from the activated site (γ-or η-site) to the chiral center of the catalyst.…”

“…On this account, a vast number of the asymmetric IEDHDA reactions have been investigated and various efficient creative substrates or intermediates possessing IEDHDA reactive activity, such as ketenes, [8] dienamines, [9] aldehydes, [10] enamines, [11] enolates, [12] and enol ethers [13] have been extensively exploited to deliver various chiral six‐membered heterocycles. Recently, the allyl ketones which widely applied to α ‐ or γ ‐selective Michael additions or aldol reactions, [14] have been successfully utilized in a remote asymmetric inverse‐electron‐demand (IED) oxa‐Diels−Alder reaction for construction of pyran skeletons [15] . Nowadays, the development of asymmetric remote activation via organocatalysis is still a challenging research topic in the area of organic synthesis because of the long distance from the activated site ( γ ‐ or η ‐site) to the chiral center of the catalyst.…”

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

“…The reaction proceeds with excellent results, showing a β,γ-regioselectivity regarding the in situ formed dienolate (Scheme 27). [42] Scheme 23. Asymmetric IEDHDAR between enals and pyrazolones.…”