The broad prospects of trifluoromethylated compounds in materials science, agricultural chemistry, and pharmaceutical chemistry have stimulated the rapid development of asymmetric organocatalytic transformations to access these biologically important compounds. Among all types of trifluoromethylated compounds, trifluoromethylated cyclic compounds with a C−CF3 stereogenic center have gained increasing attention in medicinal and organic chemistry because they are extensively found in many biologically active molecules, lead compounds, and listed drugs. This review attempts to summarize the developments in the organocatalytic asymmetric synthesis of cyclic compounds bearing a trifluoromethylated stereogenic center since 2012.magnified image

This review summarizes the recent development of novel approaches to construct structurally unique oxindoles featuring a spirocycle at the C2 position.

A chemoselective cross Rauhut-Currier-type reaction has been developed involving a tri-substituted alkene (trifluoromethyl-containing acrylonitrile derivative) with a di- or tri-substituted alkene to yield tetra-substituted double bonds in RC-type products. This approach can support the synthesis of trifluoromethylated tetra-substituted olefins and synthetically important, structurally complex 3-allylic-type oxindole skeletons. The asymmetric version of this RC-type reaction can be realized by combining a Brønsted acid and Lewis base for bifunctional H-bonding-tertiary amine catalysis. Subsequent transformation of multi-functionalized RC-type product leads to pharmacologically interesting cyclohexane-based spiro-pyrazolones bearing six contiguous chiral centers and two highly congested, vicinal quaternary carbon centers.

Highly chemo- and regioselective substrate-directed benzannulation of trisubstituted CF3-alkenes and 2-benzylidenemalononitriles or 2-nitroallylic acetates has been achieved via Michael-initiated [4 + 2] or Rauhut–Currier-initiated [3 + 3] annulation.