BF₃ ⋅ Et₂O Promoted Inverse‐Electron‐Demand Oxa‐Diels‐Alder Reaction of Alkylidene Isoxazol‐5‐ones with Unactivated Alkenes

Abstract

The synthesis of fused dihydropyran isoxazole derivatives has been developed by employing an intermolecular inverse‐electron‐demand Diels‐Alder reaction of readily available alkylidene isoxazol‐5‐ones with unactivated alkenes. The reaction was promoted by inexpensive and commercially available BF3 ⋅ Et2O without the use of metal Lewis acids. This cycloaddition transformation could proceed under mild conditions with broad substrate scope, providing a variety of bicyclic 5,6‐dihydro‐4H‐pyrano[3,2‐d]isoxazoles.

IronIII-catalyzed asymmetric inverse-electron-demand hetero-Diels–Alder reaction of dioxopyrrolidines with simple olefins

“…The generation of active dienophiles in situ , exemplified by the conversion of 3-cyclopropylideneprop-2-enone into cyclobutene-fused furans 10 or the oxidation of ethers, 11 facilitates rapid and alternative access to cycloaddition products. In contrast, IEDHDA reaction of simple alkenes is generally challenging 12,14 and achievable only by lowering the LUMO of hetero-dienes. Two successful examples involve the asymmetric [4 + 2] cycloaddition of β,γ-unsaturated α-ketoesters into chiral oxanes (Scheme 1b), as illustrated in Scheme 1b.…”

On the Brønsted acid-catalyzed aza-Michael reaction of isoxazol-5-ones to enones: reaction optimization, scope, mechanistic investigations and scale-up

“…[11][12][13][14][15][16] Recent studies provided evidence that this class of substrates still has a great synthetic potential to be further explored. [17][18][19][20][21][22][23] The application of isoxazol-5-ones is not limited to synthetic chemistry, with a diversity of isoxazol-5-one derivatives presenting important biological properties, [24][25][26] such as anticancer, 27 antiulcer, 28 antioxidant, 29 analgesic 30 and antibacterial. 31 Interestingly, although 4-arylidene isoxazol-5ones have been widely described as Michael acceptors, 32 the use of other 4-substitued isoxazol-5-ones as Michael donors is still sparse.…”