Catalytic C-H Functionalization of sp3 Hybridized Bonds Adjacent to Nitrogen. New Metal Complexes for the Atom Economic Synthesis of α-Chiral Primary Amines Eugene Chong, Philippa R. Payne, Laurel L. Schafer Department of Chemistry, The University of British Columbia, Vancouver, BC, Canada Hydroaminoalkylation, or the direct α-alkylation of amines, is an attractive synthetic approach for preparing substituted amines. Often, desired hydroaminoalkylation products are accompanied by hydroamination byproducts. A detailed understanding of the catalytic mechanism provides insight for catalyst design to access one reaction manifold over another. Pyridonates show the best reactivity thus far. R1
NH2 R'
R'
n n = 0, 1, 2
R'
H N
NH2
cat.
Ti
targeted reaction
R' R"
n
Pyridonates promote desired hydroaminoalkylation! WHY?
O (NMe2)2
N vary sterics
R2
2 vary electronics
Preferred Modular Family of Precatalysts
Remaining Goals : Reaction Kinetics (by NMR spectroscopy) Show : - First order in substrate - KIE indicates turnover limiting C-H activation - Eyring analysis consistent with highly order transition state
- Isolate organometallic reactive intermediates for mechanistic investigations - Extend reactivity to intermolecular version - Prepare new catalysts for diastereoselective and enantioselective variants
