Catalytic Asymmetric 1,3‐Dipolar Cycloaddition of β‐Fluoroalkylated α,β‐Unsaturated 2‐Pyridylsulfones with Nitrones for Chiral Fluoroalkylated Isoxazolidines and γ‐Amino Alcohols

Abstract

2-Pyridylsulfone-and fluoroalkylated group-activated olefins underwent highly efficient diastereo-and enantioselective 1,3-dipolar cycloadditions across various aromatic and aliphatic nitrones in the presence of ac hiral Ni II / bis(oxazoline) catalyst. The process was tuned by 4 molecular sieves,chiral bis(oxazoline) ligands,reaction solvents,and temperature.Awide arrayo fo ptically pure fluoroalkylated isoxazolidines were obtained, thus facilitating the asymmetric synthesis of an enantioenriched a-trifluoromethylated g-amino alcohol in gram-scale and at rifluoromethylated derivative of 1,3-oxazinan-2-one with potential pharmaceutical interest. A stereochemical model, based on the absolute configuration of one adduct and some control experiments,w as postulated to account for the observed endo-and enantioselectivity.

Stereospecific Synthesis of Fluorinated Pyrazolidinones and Isoxazolidines via a Catalyst‐Free 1,3‐Dipolar Cycloaddition of β‐Fluoroalkylated α,β‐Unsaturated 2‐Pyridylsulfones

“…When we initially used 1 a and azomethine imine 1,3‐dipole 2 a for chiral N,N′ ‐bicyclic pyrazolidinone under Lewis acidic and 4 Å MS conditions, very low enantioselectivity and yield were observed. Control experiment in CH 2 Cl 2 revealed that 4 Å MS has a detrimental effect on the yield and diastereoselectivity (Table , entry 1), which is quite different from our previous investigation with nitrones …”

Synthesis of Some novel Azomethine Oxide Derived from Aromatic Oximes and their Anti-microbial Studies

“…This reaction forms the N-O double bond and creates a stable nitronate intermediate, which can be isolated or used directly in subsequent reactions (Murahashi and Imada, 2019). One of the most notable characteristics of nitrones is their ability to undergo 1,3-dipolar cycloaddition reactions with alkenes or alkynes, known as the "nitrone-alkene/alkyne" cycloaddition (Yang, et al, 2017;Alshreimi, et al, 2020). This reaction forms isoxazolidine or isoxazole derivatives, depending on the specific conditions used (Qaddo and Abed, 2022;Li, et al, 2021).…”

“…Nitrones are widely used in the synthesis of natural products, pharmaceuticals, and other biologically active compounds (Mohammed and Salih, 2022). They have been employed in the development of drugs for various therapeutic areas, including neurodegenerative diseases, cancer, antimicrobial, antitumor, anti-inflammatory properties, and infectious diseases (Yang, et al, 2017;McKay, et al, 2011;Sandmeier and Carreira, 2021). In addition to their synthetic applications, nitrones also exhibit antioxidant properties, which make them useful in the fields of free radical biology and medicine (Floyd, et al, 2002;Floyd, et al, 2008).…”

Catalytic Asymmetric Tandem Cycloisomerization/[5+2] Cycloaddition Reaction of N-Aryl Nitrone Alkynes with Methyleneindolinones

“…N itrone is a kind of widely used 1,3-dipole in cycloadditions, giving various five-membered isoxazolidines, which have been well studied. 1,2 It was also found that 2ethynylphenyl-substituted nitrones could form other useful isoquinoline-containing cyclic azomethine ylides in the presence of transition metal salts, through N−O bond cleavage and the addition of imine to α-carbonyl carbenoid (Scheme 1a). 3 These cyclic azomethine ylides can be applied to the dipolar cycloadditions, leading to the easy construction of seven-membered nitrogen bridge rings.…”