posted on 2023-05-22, 18:06authored byNaudin van den Heuvel, Savannah M. Mason, Brandon Q. Mercado, Scott J. Miller
Amination
of C(sp3)–H bonds is a powerful tool
to introduce nitrogen into complex organic frameworks in a direct
manner. Despite significant advances in catalyst design, full site-
and enantiocontrol in complex molecular regimes remain elusive using
established catalyst systems. To address these challenges, we herein
describe a new class of peptide-based dirhodium(II) complexes derived
from aspartic acid-containing β-turn-forming tetramers. This
highly modular system can serve as a platform for the rapid generation
of new chiral dirhodium(II) catalyst libraries, as illustrated by
the facile synthesis of a series of 38 catalysts. Critically, we present
the first crystal structure of a dirhodium(II) tetra-aspartate complex,
which unveils retention of the β-turn conformation of the peptidyl
ligand; a well-defined hydrogen-bonding network is evident, along
with a near-C4 symmetry that renders the
rhodium centers inequivalent. The utility of this catalyst platform
is illustrated by the enantioselective amination of benzylic C(sp3)–H bonds, in which state-of-the-art levels of enantioselectivity
up to 95.5:4.5 er are obtained, even for substrates that present challenges
with previously reported catalyst systems. Additionally, we found
these complexes to be competent catalysts for the intermolecular amination
of N-alkylamides via insertion into the C(sp3)–H bond α to the amide nitrogen, yielding differentially
protected 1,1-diamines. Of note, this type of insertion was also observed
to occur on the amide functionalities of the catalyst itself in the
absence of the substrate but did not appear to be detrimental to reaction
outcomes when the substrate was present.