New Resolution of 2-Formyl-1,4-DHP Derivatives Using CIDR Methodology. Facile Access to New Chiral Tricyclic Thiolactam

(R)- and (S)-α-phenylethylamine (α-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)-α-PEA (7) or (S)-α-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.