Ligand-Controlled Chemo- and Enantiodivergent Rh(III)-Catalyzed Redox-Neutral Annulation of Aryl Hydroxamates with Cyclopropenes via C–H and C–C Activation

Asymmetric
C–H bond functionalization employing rhodium
catalysts has gained significant attention in the recent past, given
the possibility of introducing chirality at the late stage in organic
scaffolds. This strategy has been generally restricted to enantioselective
approaches, but achieving enantiodivergence and chemodivergence from
the same starting point is limited and requires possibly different
catalytic systems. Herein, we disclose that a general and efficient
ligand-controlled chemo- and enantiodivergent synthesis of isoquinolones
and isoindolinones has been achieved from aryl hydroxamates and cyclopropenes
through chiral cyclopentadienylrhodium(III)-catalyzed [4 + 2] and
[4 + 1] annulations, respectively. The reaction involves both C–H/C–C
bond activation and C–C/C–N bond formation and explores
the reactivity of cyclopropenes as both C2 and C1 synthons. These
redox-neutral transformations exhibit mild reaction conditions and
broad substrate scope as well as require catalytic amounts of additives
for the synthesis of both isoquinolones and isoindolinones in high
yields (up to 97%) and chemo- and enantioselectivity (up to 99:1 er).
These selectivities were controlled by the substituents present at
the 3,3′-position of the binaphthyl and cyclopentadienyl moieties
of the ligand. The size of both substituents differentiates the orientation
of C–H-activated species to offer high enantiodivergence, but
the substituent at the 3,3′-position of binaphthyl alone contributes
to the observed chemodivergence. The synthetic applicability of the
methods has been demonstrated through the synthetic modification of
the isoquinolones and isoindolinones and late-stage functionalization.