Rh-Catalyzed Intermolecular Reactions of Cyclic α-Diazocarbonyl Compounds with Selectivity over Tertiary C–H Bond Migration

Intermolecular Rh-catalyzed reactions of cyclic α-diazocarbonyl
compounds with chemoselectivity over β-hydride elimination are
described. These methods represent the first general intermolecular
reactions of Rh-carbenoids that are selective over tertiary β-C–H
bond migration. Successful transformations include cyclopropanation,
cyclopropenation, and various X–H insertion reactions with
a broad scope of substrates. We propose that the intermolecular approach
of substrates to carbenes from acyclic diazo precursors may be relatively
slow due to a steric interaction with the ester function, which is
perpendicular to the π-system of the carbene. For carbenes derived
from five- and six-membered cyclic α-diazocarbonyls, it is proposed
that the carbene is constrained to be more conjugated with the carbonyl,
thereby relieving the steric interaction for intermolecular reactions,
and accelerating the rate of intermolecular reactivity relative to
intramolecular β-hydride migration. However, attempts to use
α-diazo-β-ethylcaprolactone in intermolecular cyclopropanation
with styrene were unsuccessful. It is proposed that the conformational
flexibility of the seven-membered ring allows the carbonyl to be oriented
perpendicular to Rh-carbene. The significant intermolecular interaction
between the carbonyl and approaching substrate is in agreement with
the poor ability of α-diazo-β-ethylcaprolactone to participate
in intermolecular cyclopropanation reactions. DFT calculations provide
support for the mechanistic proposals that are described.