title: New resolution of 2-formyl-1,4-dhp derivatives using CIDR methodology. Facile access to new chiral tricyclic thiolactam.
abstract: (R)- and (S)-alpha-phenylethylamine (alpha-PEA: 7) have been used separately to resolve successfully a racemate 2-formyl-1,4-DHP derivative 4. The process was based on the difference of the solubility of both Schiff bases (6) since one of them crystallized out from the solution. These imines obtained by condensation of (R)-alpha-PEA (7) or (S)-alpha-PEA (7) with aldehyde (rac-4) were separated and analyzed by X-ray diffraction, and their exposition to an hydrochloric hydrolysis conditions led to the enantiopure (4R)-4 or (4S)-4 in excellent yields. Separate condensation of other chiral (8 and 13) and racemic (18) amino thiols as auxiliary with rac-4, (4S)-4, or (4R)-4 is accompanied by an in situ crystallization-induced dynamic resolution, whereby one distereomer of thiazole template selectively precipitates and can be isolated by simple filtration in 76-82% yield with dr > 99. The thiazole species isolated from this process resulted from an amino aldehyde condensation followed by a spontaneous thiol-imine cycloaddition. Finally, the racemate (+/-)-(4R,2'R)-19 and the diastereomerically pure homologous (4S,2'R)-23 and (4R,2'S)-20 (obtained in good yields (79-82%) from 2-aminoethanethiol (18) and 2-formyl-1,4-DHP derivative rac-4, (4S)-4, or (4R)-4, respectively) were converted conveniently in a one-pot procedure into newly tricyclic thiolactams in the DHP series in racemic ((+/-)-(6R,9bR)-21, 72% yield)) and enantiopure ((6S,9bR)-24, 71% yield); (6R,9bS)-24, 70% yield) forms.
authors.affiliation: Department of Organic Chemistry, Slovak University of Technology, SK-81237 Bratislava, Slovak Republic.
authors.forename: Stefan
authors.initials: S
authors.lastname: Marchalín
authors.forename: Katarína
authors.initials: K
authors.lastname: Cvopová
authors.forename: Miroslav
authors.initials: M
authors.lastname: Kriz
authors.forename: Peter
authors.initials: P
authors.lastname: Baran
authors.forename: Hassan
authors.initials: H
authors.lastname: Oulyadi
authors.forename: Adam
authors.initials: A
authors.lastname: Daïch
mesh_terms: D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry; D003460:Crystallization / Q000379:methods; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry; D007769:Lactams / Q000737:chemistry*; D008958:Models, Molecular; D013237:Stereoisomerism
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007769:Lactams