Stereoselective synthesis of atropisomeric korupensamines A and B utilizing planar chiral arene chromium complex.

Abstract

Naphthyl tetrahydroisoquinoline alkaloids, atropisomeric korupensamines A and B and ent-korupensamine B, were synthesized by syn-selective cross-coupling of a planar chiral arene chromium complex with naphthylboronic acid and subsequent axial isomerization or tricarbonylchromium migration to the inverted arene face as a key step. Palladium(0)-catalyzed cross-coupling of planar chiral arene chromium complex 12 with naphthylboronic acid 9 gave syn-biaryl coupling product 13. syn-Biaryl chromium complex 13 was heated in 1:1 mixture of di-n-butyl ether and 1,2-dichloroethane to give a face-inverted anti-biaryl chromium complex 14 without axial isomerization. Korupensamine A was synthesized from the syn-biaryl chromium complex 13 via o-formyl syn-biaryl chromium complex 10, and ent-korupensamine B was prepared from the face-inverted anti-biaryl chromium complex 14. On the other hand, difluoro-substituted syn-biaryl chromium complex 40 with a formyl group afforded anti-biaryl chromium complex 41 containing a rotated central bond by heating in xylene. The chromium-complexed fluorine atom was easily substituted with an isopropoxy group by nucleophilic substitution. Use of these reactions allowed (+)-2-bromo-3,5-difluorobenzaldehyde chromium complex (37) as a single chiral source to be converted to atropisomeric korupensamines A and B, respectively.