Olefin Amine (OLA) Reagents for the Synthesis of Bridged Bicyclic and Spirocyclic Saturated N‑Heterocycles by Catalytic Hydrogen Atom Transfer (HAT) Reactions

Spiro- and bridged bicyclic structures
are in demand for their
sp3-rich frameworks that offer unique physiochemical properties
and precisely positioned substituent groups. In order to rapidly access
such molecules in a cross-coupling fashion we describe olefin amine
(OLA) reagents for the transformation of aldehydes and ketones into
all three topological types of bicyclic N-heterocycles: bridged, spiro-,
and fused rings. The OLA reagents are easily prepared and allow the
synthesis of complex molecular frameworks under operationally simple
conditions that tolerate a wide array of functional groups. Investigations
into the Mn or Fe promoted reaction pathway support a metal hydride
hydrogen atom transfer (MH-HAT) to generate a C-centered radical that
undergoes addition to an unactivated imine, leading to an N-centered
radical. A catalytic cycle featuring regeneration of the metal catalyst
by O2 and a second HAT to form the unprotected saturated
N-heterocycle appears to be operative.