Organocatalyzed Sulfa-Michael Addition of Thiophenols on Trisubstituted α‑Fluoroacrylates, a Straightforward Access to Chiral Fluorinated Compounds

In
this manuscript, a simple and efficient sulfa-Michael addition
reaction of aryl thiols to trisubstituted α-fluoro-α,β-unsaturated
esters both in racemic and, for the first time, in enantioselective
version is reported. The commercially available dimer of cinchona
derivatives (DHQ)2PYR was used as a catalyst. This strategy
showed a great tolerance for various substrates and substituents,
providing fair to excellent yields, moderate to excellent diastereoselectivities
(2:1 to >99:1), and low to good enantioselectivities (2 to 87%).
The
reaction has been applied to the synthesis of fluorinated analogues
of diltiazem and tiazesim, both therapeutic agents.