Conformational analysis—LXXX

Relative Stability of cis- and trans-Hydrindanones

“…The methylated compound 2c was more stable than 2t , demonstrating that the additional methyl group had negligible effect on the relative stability of this system (Scheme 2) [3]. However, the isopropyl group reversed the relative stabilities of 3c and 3t because the methyl group of the isopropyl group strongly interacted with the juncture methyl group in the cis -isomer 3c , although the heat of formation of 3c was less than that of 3t [3]. The equilibrium ratio was 61:39 in compounds 4c and 4t , in favor of the cis -isomer 4c [3].…”

“…However, the isopropyl group reversed the relative stabilities of 3c and 3t because the methyl group of the isopropyl group strongly interacted with the juncture methyl group in the cis -isomer 3c , although the heat of formation of 3c was less than that of 3t [3]. The equilibrium ratio was 61:39 in compounds 4c and 4t , in favor of the cis -isomer 4c [3]. In the case of compounds 5c and 5t , the ratio was 99:1 in equilibrium [3].…”

“…Hydrindanones are important intermediates in bioactive natural product synthesis [1,2]. cis -Hydrindanones are widely considered to be more stable than the corresponding trans -isomers and this is partly because C/D- trans steroid ketones at the C-15 position can isomerize to the corresponding cis isomers with base treatment [3]. However, the stability of hydrindanones is now known to depend on the ring system.…”

“…For example, the trans -derivative 1t can be epimerized into the cis -derivative 1c (the suffix “c” denotes cis and “t” trans for the ring junction) by a simple isomerization reaction. Allinger discussed the relative energies of both cis and trans isomers calculated by MM2 [3]. Thus, 1c was more stable than 1t , as shown in Scheme 1 (the figures in the parentheses are heat of formation values as calculated by MOPAC6).…”

The reactions of B-norsteroidal 4- and 5-enes

“…In general, a trans fused 6:6-decalin is more stable than the cis isomers whilst the reverse is true for the 6 : 5 fusion of a hydrindane. [1][2][3] This can affect the stereochemistry of those reactions which are under thermodynamic control.…”