Spiroborate ester-mediated asymmetric synthesis of beta-hydroxy ethers and its conversion to highly enantiopure beta-amino ethers.
Borane-mediated reduction of aryl and alkyl ketones with alpha-aryl- and alpha-pyridyloxy groups affords beta-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 beta-hydroxy ethers are successfully converted to beta-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 beta-2,3-dihydro-1H-isoindol ethers. Nonracemic Mexiletine and nAChR analogues with potential biological activity are also synthesized in excellent yield by mesylation of key beta-hydroxy pyridylethers and substitution with five-, six-, and seven-membered ring heterocyclic amines.
Department of Chemistry, University of Puerto Rico-Humacao, CUH Station, Humacao, Puerto Rico.
Kun
K
Huang
Margarita
M
Ortiz-Marciales
Wildeliz
W
Correa
Edgardo
E
Pomales
Xaira Y
XY
López
D000588:Amines / Q000138:chemical synthesis*; D001881:Borates / Q000737:chemistry; D004987:Ethers / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D013141:Spiro Compounds / Q000737:chemistry
D000588:Amines; D001881:Borates; D004987:Ethers; D006571:Heterocyclic Compounds; D013141:Spiro Compounds