Reductive Labilization of a Cyclometalating Ligand Applied to Auxiliary-Mediated Asymmetric Coordination Chemistry

(4S)-4-Isopropyl-2-(3-nitrophenyl)-4,5-dihydrooxazole ((S)-Phox) is introduced as a novel chiral auxiliary
for the asymmetric synthesis of ruthenium polypyridyl complexes. A
simply accessible (S)-Phox-bearing precursor
serves as the starting point for diastereoselective coordination chemistry:
The stereogenic carbon atom of the cyclometalating auxiliary controls
the spatial arrangement of incoming 1,10-phenanthrolines during ligand
substitution reactions (ratio Λ:Δ up to 14:1), and further
precipitation affords diastereopure compounds. In the following key
step, the labilization of the auxiliary ligand is achieved by reduction,
thus permitting its replacement against a third polypyridyl ligand
with complete retention of the configuration at the metal center (er >
99:1) under mildly acidic conditions, in contrast with previously
developed systems that require strong acid. On the basis of results
of NMR experiments and X-ray analysis obtained for intermediate compounds,
mechanistic considerations for the formation of diastereomeric complexes
were made, revealing a Δ → Λ isomerization as the
reason for the observed limitations in selectivity optimization. This
work expands the pool of methods available for the asymmetric synthesis
of tris-heteroleptic ruthenium polypyridyl complexes and additionally
may serve as an inspiration for the synthesis of other nonracemic
octahedral chiral-at-metal compounds.