Organocatalytic Stereoselective Synthesis of Acyclic γ‑Nitrothioesters with All-Carbon Quaternary Stereogenic Centers

A method
for the stereoselective synthesis of acyclic thioesters
bearing adjacent quaternary and tertiary stereogenic centers under
mild organocatalytic conditions was developed. α-Substituted
monothiomalonates (MTMs) were used as thioester enolate equivalents.
They reacted cleanly with nitroolefins in the presence of 1–6
mol % of cinchona alkaloid urea derivatives, and provided access to
γ-nitrothioesters with quaternary stereocenters in high yields
and diastereo- and enantioselectivities. Mechanistic investigations
provided insight into the parameters that determine the stereoselectivity
and showed that the diastereoselectivity can be controlled by the
nature of the MTM substrate. The different reactivities of the three
functional groups (oxoester, thioester, nitro moieties) within the
conjugate addition products allowed for straightforward access to
other compounds with quaternary stereogenic centers, such as γ-nitroaldehydes
and γ-butyrolactams.