Crystal structures and conformations of shiromodiol 8-O-angelate and of the corresponding 6-ketone

Abstract

The X-ray crystal structures of shiromodiol 8-O-angelate (3) and of the corresponding 6-ketone (4) were determined by direct methods from 1 164 and 1 005 independent reflections respectively and refined to R 0.052 and 0.049. Both compounds are orthorhombic, space group P2₁2₁2₁. The results show that oxidation of the chair-boat germacrane alcohol (3) to the ketone (4) is accompanied by a conformational inversion of the molecular fragment C(5)⋯ C(10), since compound (4) exists in the solid state as a double-chair rotamer with the methyls syn-oriented on the α-face of the molecule and the isopropyl side-chain β axial. This represents a previously unobserved conformational geometry for germacrane derivatives and it is present also in solution. The flipping from the chair-boat to the chair-chair conformation removes a transannular interaction between the protons βH(5) and β-H(8) as well as the Pitzer strain and a non-bonded interaction between the oxo group and the isopropyl side-chain. All this overrides the effect of steric congestion, in the chair-chair conformation of (4), between the methyl group at C(10) and the oxygen atom at C(8), the separation of which is ca. 0.4 Å less than the sum of the van der Waals radii.