New key compounds in cyclotriveratrylene chemistry. Synthesis, optical resolution, absolute configuration and circular dichroism of C3-cyclotriveratrylenes with sulfur substituents

Abstract

Vanillin 6a and isovanillin 6b were converted via a Newman-Kwart rearrangement to thiovanillin 9a and isothiovanillin 9b, which on S-methylation and subsequent reduction of the aldehyde function gave 3-methoxy-4-methylthio- (3a) and 4-methoxy-3-methylthio-benzylalcohol (3b), respectively. On reaction with formic acid, 3a and 3b afforded in excellent yield the new sulfur substituted cyclotriveratrylene 4. The latter could be desulfurized to cyclotrianisylene 2b, and selectively O-demethylated to the triphenol 11. Optical resolution of 11 gave access to a new family of chiral cyclotriveratrylenes incorporating sulfur substituents, which in turn can be used as starting units for the synthesis of new cryptophanes and related host structures. Analysis of the chiroptical properties of these sulfur substituted cyclotriveratrylenes provided information on the relative influence of the CH₃O and CH₃S substituents on the electronic transitions of the benzene chromophore. It was inferred from the exciton circular dichroism spectra of these compounds that the CH₃S group exerts a weaker effect than the CH₃O group on the polarization direction of the benzenoid ¹L_b transition, the reverse being true for the ¹L_a transition.