Diastereo- and Enantioselective Construction of Biologically Important Chiral 1,3-Dioxolochroman Frameworks via Catalytic Asymmetric [4+2] Cycloaddition

A diastereo-
and enantioselective construction of biologically
important chiral 1,3-dioxolochroman frameworks has been established
via chiral phosphoric acid (CPA)-catalyzed asymmetric [4+2] cycloaddition
of ortho-quinone methides with 3-methyl-2-vinylindoles. By using this
approach, a series of indole-based chiral 1,3-dioxolochromans were
synthesized with structural diversity in generally good yields, excellent
diastereoselectivities and high enantioselectivities (up to 98% yields,
>95:5 dr, 97% ee). The evaluation on the cytotoxic activity of
some
selected products indicated that this class of chiral 1,3-dioxolochroman
derivatives had some extent of anti-cancer activity. This reaction
not only provides an efficient synthetic method for accessing chiral
1,3-dioxolochroman derivatives with structural diversity and optical
purity but also will enrich the research contents of catalytic asymmetric
[4+2] cycloadditions involving ortho-quinone methides. In addition,
the bioassay of these compounds will cast a light on discovering useful
bioactivities of chiral 1,3-dioxolochroman derivatives, which will
be helpful for finding lead compounds.