1,3‐Dipolar Cycloaddition Reactions of Indan‐1‐one Enamines across Arylnitrile Oxides Leading to Novel Cyclic Isoxazoline Derivatives

Abstract

Synthesis of a series of cyclic fused‐isoxazolines has been accomplished by regioselective and diastereoselective 1,3‐dipolar cycloaddition of 3‐methylindan‐1‐one enamines (1a, 1b, 1c) and 3‐phenylindan‐1‐one enamines (2a, 2b, 2c) to arylnitrile oxides (3d, 3e, 3f, 3g, 3h). The structure of the cycloadducts was elucidated by 1H and 13C NMR spectroscopy. The proposed regio‐ and stereochemistry of fused‐compounds (4) and (5) has also been corroborated by two single‐crystal X‐ray diffraction studies carried out on 4‐methyl‐8b‐morpholinyl‐3‐(p‐tolyl)‐4H‐3a,8b‐dihydroindeno[2,3‐d]isoxazoline (4be) and 3‐(p‐anisyl)‐4‐phenyl‐8b‐pyrrolidinyl‐4H‐3a,8b‐dihydroindeno[2,3‐d]isoxazoline (5af) and by means of density functional theory calculations.

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

“…To the best of our knowledge it is the first example of a stereoselective formation of 4-aryl(heteroaryl)isoxazolines in the reaction of acyclic enamines with nitrile oxides. The stereoselective formation of trans -4-alkylisoxazolines in the reaction of β-azolyl enamines with benzonitrile oxides was observed by Pokar et al [34] in 1980 and diastereoselective formation of fused isoxazolines was recently reported by Jelizi et al [35]. Their structures are assigned as trans -isomers which are deduced from coupling constants of 4.0 and 4.2 Hz for the C 4 –H and C 5 –H in the NMR spectra (see Supporting Information File 2 for NMR spectra descriptions and copies).…”

Cycloaddition Reactions of Enamines

“…The interaction of enamines 126 a – c derived from 1‐indanones with arylnitrile oxides 127 leads to the formation of cyclic fused‐isoxazolines 128 by regioselective and diastereoselective 1,3‐dipolar cycloaddition (Scheme 40). [42] …”

“…The interaction of enamines 126 a-c derived from 1-indanones with arylnitrile oxides 127 leads to the formation of cyclic fused-isoxazolines 128 by regioselective and diastereoselective 1,3-dipolar cycloaddition (Scheme 40). [42] Reddy et al developed a new method for obtaining Valdecoxib, which is a nonsteroidal anti-inflammatory drug. [43] The key stage of this process is the formation of isoxazole 130 from enamine 31 d and in situ-generated nitrile oxide derivatives (Scheme 41).…”