Stereoselective Synthesis of Axially Chiral Natural Products, (−)-Steganone and O,O′-Dimethylkorupensamine A, Utilizing Planar Chiral (Arene)chromium Complexes

Palladium(0)-mediated Suzuki–Miyaura cross-coupling of planar chiral (2,6-disubstituted bromobenzene)chromium complexes with o-substituted arylboronic acids in the presence of sodium carbonate under refluxing in aqueous methanol gave stereoselectively axially chiral mono Cr(CO)3-complexed biaryls. The axial stereochemistry of the cross-coupling products was found to be largely dependent on the steric bulkiness of ortho substituent of arylboronic acids and reaction conditions. The cross-coupling with o-alkyl or hydroxymethyl substituted arylboronic acids gave kinetically controlled products in which the ortho substituents were oriented in syn-configuration to the tricarbonylchromium fragment. On the other hand, o-formyl phenylboronic acid produced thermodynamically stable anti-coupling products under the same conditions. By utilizing these methodologies, biologically active axially chiral natural products, (−)-steganone and O,O′-dimethyl derivative of the natural product of korupensamine A, were stereoselectively synthesized.