Electronic effects in 1,3-dipolar cycloaddition reactions of N-alkyl and N-benzyl nitrones with dipolarophiles

Abstract

1,3-Dipolar cycloadditions afforded fast access to isoxazolidines bearing N-alkyl or N-benzyl substituents. The electronic properties of the substituents in the nitrones define the activity of the dipoles and modulate diastereoselectivity in the non-catalyzed reactions. Using a chiral one-point binding ruthenium Lewis acid catalyst, products were obtained in good yields and with excellent regio-, diastereo-, and enantioselectivity.

Structural Manipulation of Ruthenium(II) Polypyridine Nitrone Complexes to Generate Phosphorogenic Bioorthogonal Reagents for Selective Cellular Labeling

“…Remarkably, the complex reacted with BCN‐OH at an exceptionally fast rate (Figure ) and the k 2 value was determined to be 3.060±0.108 m −1 s −1 , which is at least 36 fold larger than those of the N ‐methyl nitrone complexes 1 – 4 . The accelerated reaction kinetics should originate from the presence of the more electron‐withdrawing phenyl ring at the N ‐position of the nitrone moiety ,. More importantly, the reactivity of complex 5 toward the BCN‐modified substrate was markedly higher (up to ≈278 fold) than that of iridium(III) nitrone complexes ( k 2 ≈0.116–0.238 m −1 s −1 ), other organic acyclic nitrone derivatives ( k 2 ≈0.011–1.660 m −1 s −1 ), and benzyl azide ( k 2 ≈0.040 m −1 s −1 ) reported in the literature.…”

Regio- and diastereoselectivity of the 1,3-dipolar cycloaddition of α-aryl nitrone with methacrolein. A theoretical investigation

“…7 Several experimental studies on the regio-, enantio-and endo/exo diastereoselective synthesis of 13DC reactions of nitrones can be found in the literature. 8 Nitrones bearing various substituents at the nitrogen atom of the nitrone were synthesized by Bãdoiu et al 9 in order to expand the range of transformations that can be carried out on the isoxazolidine core following the 13DC reaction. In this series, the N-i-Pr (see Scheme 2) and -t-Bu nitrones, respectively, gave the products in moderate yields despite long reaction times and a two-fold excess of methacrolein.…”

“…In the present work, we present a theoretical study of the regio-, stereo-and diastereoselectivity of the non-catalyzed 13DC of N-iso-propyl,a-(4-triuoromethyl)-phenyl nitrone 1 and methacrolein 2, experimentally studied by Bãdoiu et al 9 (see Scheme 2). We note that the best yields of diastereoselectivities (in favour of the endo isomer) have been obtained in the case of non-catalyzed reaction (in comparison of the catalyzed one) using the N-i-Pr and t-Bu nitrones and exclusively the 3,5-substituted regioisomers were isolated (see Scheme 2).…”

“…We note that the best yields of diastereoselectivities (in favour of the endo isomer) have been obtained in the case of non-catalyzed reaction (in comparison of the catalyzed one) using the N-i-Pr and t-Bu nitrones and exclusively the 3,5-substituted regioisomers were isolated (see Scheme 2). 9 Firstly, in order to justify the most favoured cyclisation approach, we have performed a density functional theory (DFT) study with the aim to localize the stationary points for reactants, transition structures (TSs), cycloadducts (CAs) of all the possible regio-and stereoisomeric channels on the potential energy surface (PES). Then, the reaction mechanism is discussed and analysed on the basis of the intrinsic reaction coordinate (IRC) calculations and the topological analysis of the electron localization function (ELF).…”

Asymmetric Syntheses of Analogs of Kainic Acid

“…[ Badoiu, A. and Kundig, E. P. 2012] who determined that the formed exo diastereomer increased with the increasing electron-withdrawing character of substituent in dipolarophiles in non-catalyzed 1, 3 dipolar cycloaddition reaction between 4-(trifluoromethyl)benzylidene methylamine N-oxide and 3, 5-substituted isoxazolidines.…”