Spiroborate Ester-Mediated Asymmetric Synthesis of β-Hydroxy Ethers and Its Conversion to Highly Enantiopure β-Amino Ethers

Abstract

Borane-mediated reduction of aryl and alkyl ketones with α-aryl-and α-pyridyloxy groups affords β-hydroxy ethers in high enantiomeric purity (up to 99% ee) and in good yield, using as catalyst 10 mol % of spiroborate ester 1 derived from (S)-diphenylprolinol. Representative β-hydroxy ethers are successfully converted to β-amino ethers, with minor epimerization, by phthalimide substitution under Mitsunobu's conditions followed by hydrazinolysis, to obtain primary amino ethers or by imide reduction with borane to afford β-2,3-dihydro-1H-isoindol ethers. Non-racemic Mexiletine and nAChR analogues with potential biological activity are also synthesized in excellent yield by mesylation of key β-hydroxy pyridylethers and substitution with 5, 6 and 7 member ring heterocyclic amines.

Recent contributions to the Diversity-Oriented Synthesis (DOS) mediated by iminium ions through multicomponent Mannich-type reactions

“…[28][29][30] In the past years, a series of selective serotonine (5-HT)-reuptake inhibitor (SSRI) antidepressants (e.g. Fluoxetine and Paroxetine) and selective norepinephrine (NE)-reuptake inhibitor antidepressants (e.g.…”

Dibenzylammonium hydrogen maleate and a redetermination at 120 K of bis(dibenzylamino)methane

“…2). Aminoethers are valuable building blocks in organic synthesis as they are important precursors in the synthesis of a wide range of pharmaceutical products (Pinder & Wieringa, 1993;Franchini et al, 2003;Cavalluzzi et al, 2007;Huang et al, 2009). In recent years, a series of selective serotonin (5-HT)reuptake inhibitor antidepressants (e.g.…”

Synthesis of Zeolite Beta and Zeolite ZSM-5 from High Silica Raw Kaolinite and Their Catalytic Etherification of Ethylene Glycol

“…To our best of knowledge, catalytic etherification of ethylene glycol with alcohols to produce ethylene glycol monoalkyl ethers (EGMEs) using zeolites has not been reported. This important class of β-hydroxy ethers [28][29][30] was commercially produced via catalytic alcoholysis of alkylene oxides [31,32] reductive cleavage of cyclic acetals or ketals in the presence of hydrogenation active catalyst [32][33][34] and the catalytic alkylation of diols with alkyl halide [35]. Etherification of ethylene glycol with 1-octene using heteropoly acid supported on clay was recently reported [36].…”