Oxidative Cyclization of β-Aminoacrylamides Mediated by PhIO: Chemoselective Synthesis of Isoxazoles and 2H-Azirines

Abstract

Cyclization of a variety of β-aminoacrylamides in the presence of iodosobenzene (PhIO) is described. This process features mild reaction conditions, simple execution, and high chemoselectivity and thereby provides an efficient protocol for the divergent synthesis of substituted isoxazoles and 2H-azirines via switchable N–O and N–C bond formation controlled by simply varying the β-substituent R3 of the readily available substrates.

A Formal [3+2] Annulation of β‐Oxoamides and 3‐Alkyl‐ or 3‐Aryl‐Substituted Prop‐2‐Ynyl Sulfonium Salts: Substrate‐Controlled Chemoselective Synthesis of Substituted γ‐Lactams and Furans

“…As such, it is not hard to understand why α ‐benzyl β ‐oxoamides 1 g and 1 h bearing a butyl or benzyl R 1 group showed different reaction behavior from other α ‐monosubstituted β ‐oxoamides 1 with N ‐aryl amide groups. While R 3 is H, a planar conjugated enolate anion E is favored for the formation of intramolecular N−H ⋅⋅⋅ O hydrogen bond, and the charge on the O ‐atom is easily delocalized within this system . Enolate E undergoes intramolecular O ‐alkylation to afford dihydrofuran F , followed by isomerization through a 1,3‐H shift to give the final trisubstituted furan 4…”

“…While R 3 is H, a planar conjugated enolate anion E is favored for the formation of intramolecular NÀ H ··· O hydrogen bond, [17] and the charge on the O-atom is easily delocalized within this system. [18] Enolate E undergoes intramolecular Oalkylation to afford dihydrofuran F, [19] followed by isomerization through a 1,3-H shift to give the final trisubstituted furan 4. [20]…”

Synthesis of various functionalized 2H‐azirines: An updated library

“…Comparably, by using PhIO as an oxidant, a variety of β‐aminoacrylamide oxidative cyclizations had been developed by Li et al to synthesize substituted 2 H ‐azirines, with highly chemoselective NC bond formation, controlled by the β‐substituents of the substrate (Scheme 67) [90].…”

Tf2O-Mediated Cyclization of α-Acyl-β-(2-aminopyridinyl)acrylamides: Access to N-Substituted 4H-Pyrido[1,2-a]pyrimidin-4-imines

“…13,14 Notably, this amide activation strategy has been also applied to the concise synthesis of some natural products. 15 Inspired by these works and our continued research interest in developing novel and efficient synthetic methods for highly valuable heterocycles from a variety of αacylacrylamides, 16 we set out to explore the reactions of α-acylβ-(2-aminopyridinyl)acrylamides mediated by triflic anhydride. After a series of detailed investigations, we achieved a facile and efficient direct synthesis of N-substituted 4H-pyrido[1,2a]pyrimidin-4-imines under very mild conditions (Scheme 1C).…”