Total Synthesis of (−)-Rhazinilam:  Asymmetric C−H Bond Activation via the Use of a Chiral Auxiliary

The antitumor agent (-)-rhazinilam was synthesized in three major steps, namely the pyrrole synthesis, selective CbondH bond activation, and direct macrolactam formation. The key step involved asymmetric CbondH bond functionalization (dehydrogenation) of the diethyl group segment in intermediate 6. This was achieved by the attachment of chiral platinum complexes to the proximal nitrogen atom. A high degree of selectivity (60-75% ee) was achieved via the use of oxazolinyl ketone chiral auxiliaries.