Organocatalytic Enantioselective [4+3]‐Cycloadditions of Azaoxyallyl Cations with 2‐Aminophenyl Enones

Abstract

The first organocatalytic asymmetric [4 + 3]-cycloaddition of 2-aminophenyl α,β-unsaturated carbonyls with in situ generated azaoxyallyl cations was developed, and enantioenriched functionalized seven-membered 1,4-benzodiazepine-3ones were obtained in good yields and with excellent enantioselectivities. This approach was also extended to the first asymmetric [4 + 3]-cycloaddition of δ-hydroxy α,β-unsaturated carbonyls, affording 1,4-oxazepanes in one step under mild conditions. Several of the novel adducts demonstrated promising bioactivity in the prevention of peripheral nerve degeneration.

Aza‐oxyallyl Cations and Their Applications in (3+m) Cycloaddition Reactions

“…[52] In 2021 Kim and group synthesized enantioselective (up to 99 % ee) seven-membered 1,4-benzodiazepine-3-ones 110 which is an important scaffold in many natural products with in-situ generated aza-oxyallyl cation and 2-aminophenyl α-βunsaturated carbonyls 109 via asymmetric catalytic (4 + 3) cycloaddition reaction using chiral squaramide based organocatalyst (Scheme 33). [53]…”

[4 + 2] Annulation of δ-Hydroxy/δ-Sulfonamido-α,β-Unsaturated Ketones with Azlactones for Diastereoselective Synthesis of Highly Substituted 3-Amino-δ-Lactones and 3-Amino-δ-Lactams

“…However, to the best of our knowledge, the [4 + 2] annulation reaction of azlactones for the construction of δ-lactams has not been reported. , Gong et al described the three-component [4 + 2] annulation of azlactones, cinnamaldehydes, and primary amines to produce 3-amino-3,4-dihydropyridinone which provided 3-amino-δ-lactam after reduction with triethylsilane . Based on our previous research, we envisaged the [4 + 2] annulation of δ-sulfonamido-α,β-unsaturated ketones with azlactones, in which the nucleophilic C-4 and electrophilic C-5 atoms serve as a 1,3-dipole. The reaction of the nucleophilic sulfonamido group with the electrophilic C-5 atom and simultaneous Michael addition of a nucleophilic C-4 atom to the α,β-unsaturated ketone directly produced 3-amino-δ-lactam (Scheme eq d).…”

Organocatalytic Asymmetric [3 + 2]-Annulations of γ-Sulfonamido/γ-Hydroxy-α,β-Unsaturated Ketones with CyclicN-Sulfimines: Synthesis of Chiral Polyheterotricyclic Imidazolidines and Oxazolidines

“…Although few catalytic asymmetric approaches have been documented, the development of novel synthetic methods that allow efficient and rapid access to enantioenriched imidazolidines and oxazolidines is still highly desirable. Recently, we have described an efficient cyclization of γ- and δ-hydroxy-α,β-unsaturated carbonyls with azaoxyallyl cations to yield enantioenriched N , O -heterocycles . On the basis of our previous work, we wished to develop an organocatalytic annulation procedure for the construction of polyheterocycles.…”