Mechanistic Insight into Asymmetric N–H Insertion Cooperatively Catalyzed by a Dirhodium Compound and a Spiro Chiral Phosphoric Acid

The
insertion of a carbenoid into an N–H bond of an amine
cooperatively catalyzed by a dirhodium catalyst and a spiro chiral
phosphoric acid has been investigated in detail using density functional
theory methods. Calculations indicate that the reaction begins with
the nucleophilic amine attacking at the carbenoid, forming a metal-associated
ammonium ylide first followed by a rapid proton transfer to afford
a metal-associated enamine intermediate. Subsequently, the enamine
intermediate dissociates from the metal and yield a more stable seven-membered-ring
conformation via an intramolecular hydrogen-bond exchange. Formation
of the enamine intermediate requires an overall barrier of 5.7 kcal/mol
and is exergonic by 5.1 kcal/mol. Calculations demonstrated that,
although the conversion of the achiral enamine into the N–H
insertion product can be facilitated efficiently by the dirhodium
catalyst through a two-step process, it can be compressed to a large
extent. This is due to the more competitive decomposition of the diazoacetate
catalyzed by the dirhodium catalyst, which can give a carbenoid for
the next catalytic cycle. Meanwhile, formation of the carbenoid is
considerably exergonic, which can promote the direct [1,3]-proton
shift of enamine. However, in the presence of the spiro chiral phosphoric
acid, the asymmetric proton induction of enamine is greatly favored,
requiring an activation free energy of 6.0 kcal/mol to afford the
major R product. This agrees well with the experimental
observation.