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Spiroborate ester-mediated asymmetric synthesis of beta-hydroxy ethers and its conversion to highly enantiopure beta-amino ethers.

ABSTRACT: 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.

SUBMITTER: Huang K

PROVIDER: S-EPMC2767257 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Spiroborate ester-mediated asymmetric synthesis of beta-hydroxy ethers and its conversion to highly enantiopure beta-amino ethers.

Huang Kun K Ortiz-Marciales Margarita M Correa Wildeliz W Pomales Edgardo E López Xaira Y XY

The Journal of organic chemistry 20090601 11

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 ...[more]

PMID: 19413288

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