Articolo in rivista, 2012, ENG, 10.2174/138527212800840946

Chemo-enzymatic synthesis of new chiral bipyridyl alcohols and their atropisomeric N,N-dioxides

Sanfilippo Claudia; Nicolosi Giovanni; Patti Angela

CNR - Istituto di Chimica Biomolecolare, Via Paolo Gaifami 18, I-95127 Catania, Italy

New chiral bipyridyl alcohols and the corresponding N,N-dioxide derivatives were obtained with high enantiomeric excess by a chemo-enzymatic procedure. Metalation of commercial 6,6'-dimethyl-2,2'-bipyridine followed by reaction with acetaldehyde furnished an inseparable 1:1 mixture of dl- and meso- 6,6'-bis(2-hydroxypropyl)-2,2'-bipyridine ((±)-7a and meso-7b) that was subjected to lipasecatalysed enantioselective esterification with vinyl acetate in organic solvent. Immobilised Mucor Miehei lipase (Lipozyme ® IM) displayed high stereoselectivity and unreacted alcohol (S,S)-7a, monoacetyl derivative (R,S)-6 and diacetate (R,R)-9 were obtained in high optical purities as the result of the simultaneous resolution of the racemate and desymmetrization of meso isomer. After separation, the chiral compounds were converted into the corresponding N,N-dioxide derivatives with additional axial chirality stereoselectively induced during the N,N-oxidation and some considerations about their stereochemistry and atropisomeric stability were deduced by circular dichroism spectroscopy.

Current organic chemistry 16 (13), pp. 1636–1644

Keywords

Atropoisomers, Bipyridine, Circular dichroism, Lipase, N-N-oxidation

CNR authors

Sanfilippo Claudia, Nicolosi Giovanni, Patti Angela

CNR institutes

ICB – Istituto di chimica biomolecolare