Enantiospecific Synthesis of Planar Chiral Rhodium and Iridium Cyclopentadienyl Complexes: Enabling Streamlined and Computer-Guided Access to Highly Selective Catalysts for Asymmetric C–H Functionalizations

Chiral cyclopentadienyl
(CpX) metal complexes
are frequently
used in asymmetric catalysis by virtue of their high reactivity and
selectivity. Planar-chiral-only rhodium and iridium cyclopentadienyl
complexes are particularly promising due to unrestricted chemical
space for CpX ligand design while retaining structural
simplicity. However, they are currently still niche because of a lack
of efficient synthetic strategies that avoid lengthy chiral auxiliary
routes or chiral preparatory HPLC resolution of the complexes. To
streamline access to such planar-chiral-only CpX-metal
complexes, we designed a straightforward, highly enantiospecific,
point-to-planar chirality transfer complexation via facially selective
concerted-metalation-deprotonation between metal-carboxylate precursor
[M(olefin)2OAc]2 and a chiral cyclopentadiene.
This entirely avoids the typical stereoablative complexation of an
achiral cyclopentadienyl anion that detrimentally yields a racemate.
Exploiting the described enantiospecific complexation protocol and
a simple divergent synthetic route to suitable chiral cyclopentadienes,
we generated a structurally diverse library of new planar chiral Cp-Rh(I),
Cp-Ir(I), Cp-Rh(III), and Cp-Ir(III) complexes. Moreover, the enantiospecific
complexation step can be concatenated with a preceding Au-catalyzed
cyclization in an efficient one-pot process that likely involves an
elaborate point-to-axial-to-point-to-planar chirality transfer. Guided
by computational selectivity predictions, the structure of a CpX-Rh complex in our library was tuned to optimize reactivity
and selectivity in the asymmetric C–H functionalization of
a benzamide with various challenging alkenes. With an optimized CpX-Rh complex in hand, we showcased its excellent catalytic
performance and high selectivity for refractory alkene substrates
that reacted in poor selectivity with previous CpX-Rh catalysts.