Organocatalytic Enantioselective 1,6‐aza‐Michael Addition of Isoxazolin‐5‐ones to p‐Quinone Methides

Abstract

A thiourea-Brønsted base bifunctional catalyst allowed the enantioselective 1,6-aza-Michael addition of isoxazolin-5-ones to p-quinone methides to give isoxazolin-5-ones having a chiral diarylmethyl moiety attached to the N atom with fair to good yields and enantiomeric excesses. To the best of Asymmetric conjugate addition reactions constitute one of the most powerful and efficient methods for the enantioselective construction of C-C and C-X bonds. Excellent levels of regio-(1,4-vs.

Asymmetric Synthesis of Isoxazol-5-ones and Isoxazolidin-5-ones

“…In 2020 Pedro, Blay, and co-workers 33 and Wang, Xu, and co-workers 34 independently described the enantioselective 1,6-aza-Michael addition of isoxazol-5-ones to p-quinone methides 49 using thiourea-and squaramidecontaining Brønsted base bifunctional catalysts C5 and C6, respectively, to give isoxazol-5-ones 50 with a chiral diarylmethyl moiety attached to the nitrogen atom in fair to good yields and enantiomeric excesses (Scheme 7). The protocol was also effective on a gram scale.…”

Recent Advances in Selected Asymmetric Reactions Promoted by Chiral Catalysts: Cyclopropanations, Friedel–Crafts, Mannich, Michael and Other Zinc-Mediated Processes—An Update

“…Enantioselective 1,6-aza-Michael addition reaction of 4(H)-isoxazol-5-ones 70 to pquinone methides 71 promoted by various organocatalysts was described by Blay and Pedro et al [73]. The isoxazol-5-one ring is present in many natural compounds, and there are many examples of compounds from this group that are inhibitors of various enzymes.…”

“…The properties of this ring mean that some derivatives are successfully used in photonics. The desired isoxazolin-5-one derivatives 72 were formed with the greatest efficiency in dichloroethane (DCE) at room temperature in the presence of 3Å molecular sieves under action of thiourea system 73 (Scheme 28) [73]. Scheme 28.…”

Synthesis of aza‐diarylmethines via 1,6‐conjugate addition/aromatization of para‐quinone methides and isatin catalyzed by Et3N

“…The reaction of carbon atom nucleophiles have been well studied during the past years. [7][8][9][10][11][12] The reaction of sulfur, [13] phosphorus, [14] silicon, [15] boron [16,17] and nitrogen [18,19] nucleophiles have been reported. Liao' group and Tortosa's group have reported enantioselective copper-catalyzed 1,6-conjugate addition of bis(pinacolato)diboron and p-QMs.…”

“…[ 13 ] Pedro and Blay's group have reported 1,6‐aza‐Michael addition of isoxazolin‐5‐ones to p ‐QMs catalyzed by thiourea‐Brønsted base bifunctional catalyst to get isoxazolin‐5‐ones having chiral diarylmethyl moiety. [ 18 ] 1,6‐Aza‐Michael Addition of Heterocyclic Amines and Amides to para‐Quinone Methides catalyzed by NaH has been reported by Panda's group. [ 19 ] Herein, we wish to firstly report a new and effective organocatalytic 1,6‐conjugate addition/aromatization of p ‐QMs and isatin catalyzed by Et 3 N to construct aza‐diarylmethines (Scheme 1).…”