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Abstract:
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The configuration of a chiral center in semisynthetic (2)-(2R,5R,5aR,8f,9aS)-
2,8-dibromo-2,5,9,9a-tetrahydro-5-hydroxy-5,8,10,10-tetramethyl-6H-2,5a-methano-1-benzoxepin-
7(8H)-one (3 or 4), prepared in two steps from (2)-(2R,5R,5aR,7S,8S,9aS)-2,
7-dibromo-8-chloro-2,5,7,8,9,9a-hexahydro-5,8,10,10-tetramethyl-6H-2,5a-methano-1-benzoxepin-
5-ol, known as pacifenol 1, has been determined using vibrational circular
dichroism (VCD) measurements. The vibrational spectra (IR and VCD) of diastereoisomers
3 and 4 were calculated using density functional theory (DFT) at the
B3LYP/DGDZVP level of theory for the two conformers that in each case account for
the total energetic distribution found in the first 10 kcal/mol range. The DFT conformational
optimization of the 8R diastereoisomer 3 indicates the cyclohexanone exists
almost exclusively in a boat conformation with a b-equatorial bromine atom and an
a-axial methyl group at the chiral center alpha to the carbonyl group, while for the 8S
diastereoisomer 4 a 5:1 conformational distribution in favor of a chair conformation with
an a-axial bromine atom and a b-equatorial methyl group is calculated, suggesting due
to well-known chair versus boat relative stabilities that the plausible diastereoisomer
would be the 8S molecule. A comparison of the IR spectrum of the reaction product with
the calculated spectra of 3 and 4 provided no means for the diastereoisomeric assignment,
while from comparison of the VCD spectra it became immediately evident that
the rearranged molecule possesses the 8R absolute configuration as shown in 3, in concordance
with a single crystal X-ray diffraction study that could be refined to an R-factor
of 2.9%. |