Enantioselective dearomative [3+2] annulation of 5-amino-isoxazoles with quinone monoimines

Abstract

The first enantioselective dearomative [3+2] annulation of 5-amino-isoxazoles with quinone monoimines was realized using a chiral phosphoric acid as catalyst. Various novel (bridged) isoxazoline fused dihydrobenzofurans bearing two continuous quaternary...

Sc(OTf)3‐Catalyzed Dearomative [3+2] Annulation of 5‐Aminoisoxazoles with Quinone Imine Ketals or Quinone Monoacetals

“…In view of the good nucleophilicity of 5‐amino‐isoxazoles in transformations developed by us [4h,10a] and Zhang et. al [10b] .…”

Enantioselective Synthesis of 2-Isoxazolines and 2-Isoxazolin-5-ones Bearing Fully Substituted Stereocenters

“…In 2015, Jiao and co-workers presented a method for the catalytic asymmetric synthesis of chiral isoxazolines 41 substituted with a hydroxymethyl group (Scheme 6). [28] This was achieved using silyl nitronates 39 and α,β-unsaturated ketones 40 in conjunction with a TfOH-activated version of Corey's oxazaborolidine catalyst (42), affording the isoxazoline products 41 in good yields (70-99%) and high enantioselectivities (90-96% ee). The authors employed a NaBH4 reduction of the intermediate isoxazoline aldehydes, which resulted in improved isolated yields, presumably due to the increased stability of the alcohol products over the aldehyde products.…”

“…The reactions generally require shorter reaction times than other methods but the low temperature of −60 C hinders the Scheme 6. Asymmetric preparation of isoxazolines 41 from silyl nitronates 39 and α,β-unsaturated ketones 40 catalyzed by Corey's oxazaborolidine (42). overall practicality of the methodology.…”

“…In 2020, Wang and Zhang reported an enantioselective dearomative [3+2] annulation reaction of 5-amino isoxazoles 93 and quinone monoimines 94 to afford interesting isoxazoline products 95 bearing both fully substituted C4 and C5-positions (Scheme 20a). [42] This reaction was accomplished using the BINOL derived phosphoric acid organocatalyst 96 to give the desired products in good yields (35-94%) with excellent enantioselectivities (81-94% ee). When examining the scope of the reaction, it was found that a wide range of different substituents were tolerated at the R 1 and R 2 positions, including alkyl, substituted phenyl groups and heteroaromatics.…”

Regiodivergent Organocatalytic Reactions

“…In general, binaphthyl is used to synthesize chiral phosphoric acid derivatives. These catalysts have been involved in several reactions including the Diels-Alder, Nazarov, Mukaiyama Aldol, Mannich, Henry, Morita-Baylis-Hillman reactions, and 1,3-dipolar cycloadditions [146][147][148][149][150][151][152][153][154].…”