One-Point Binding Ligands for Asymmetric Gold Catalysis: Phosphoramidites with a TADDOL-Related but Acyclic Backbone

Readily available phosphoramidites incorporating TADDOL-related
diols with an acyclic backbone turned out to be excellent ligands
for asymmetric gold catalysis, allowing a number of mechanistically
different transformations to be performed with good to outstanding
enantioselectivities. This includes [2 + 2] and [4 + 2] cycloadditions
of ene-allenes, cycloisomerizations of enynes, hydroarylation reactions
with formation of indolines, as well as intramolecular hydroaminations
and hydroalkoxylations of allenes. Their preparative relevance is
underscored by an application to an efficient synthesis of the antidepressive
drug candidate (−)-GSK 1360707. The distinctive design element
of the new ligands is their acyclic dimethyl ether backbone in lieu
of the (isopropylidene) acetal moiety characteristic for traditional
TADDOL’s. Crystallographic data in combination with computational
studies allow the efficiency of the gold complexes endowed with such
one-point binding ligands to be rationalized.