Chiral Bifunctional Phosphine Ligand Enabling Gold-Catalyzed Asymmetric Isomerization of Alkyne to Allene and Asymmetric Synthesis of 2,5-Dihydrofuran

The
asymmetric isomerization of alkyne to allene is the most efficient
and the completely atom-economic approach to this class of versatile
axial chiral structure. However, the state-of-the-art is limited to tert-butyl alk-3-ynoate substrates that possess requisite
acidic propargylic C–H bonds. Reported here is a strategy based
on gold catalysis that is enabled by a designed chiral bifunctional
biphenyl-2-ylphosphine ligand. It permits isomerization of alkynes
with nonacidic α-C–H bonds and hence offers a much-needed
general solution. With chiral propargylic alcohols as substrates,
2,5-disubstituted 2,5-dihydrofurans are formed in one step in typically
good yields and with good to excellent diastereoselectivities. With
achiral substrates, 2,5-dihydrofurans are formed with good to excellent
enantiomeric excesses. A novel center-chirality approach is developed
to achieve a stereocontrol effect similar to an axial chirality in
the designed chiral ligand. The mechanistic studies established that
the precatalyst axial epimers are all converted into the catalytically
active cationic gold catalyst owing to the fluxional axis of the latter.