Diastereoisomeric assignment in a pacifenol derivative using vibrational circular dichroism

• Published in: Chirality (New York, N.Y.) N.Y.), 2009, Vol.21 (Suppl. 1E), p.E208-E214
• Main Authors: Muñoz, Marcelo A., Chamy, Cristina, Carrasco, Alvaro, Rovirosa, Juana, San Martín, Aurelio, Joseph-Nathan, Pedro
• Format: Article
• Language: English
• Subjects: chamigrene; Circular Dichroism - methods; diastereoisomeric assignment; Models, Chemical; Models, Molecular; Molecular Conformation; Molecular Structure; pacifenol; relative configuration; Sesquiterpenes - chemistry; Spectrophotometry, Infrared; Stereoisomerism; VCD; Vibration; X-Ray Diffraction; X-Rays
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.20801

The configuration of a chiral center in semisynthetic (−)‐(2R,5R,5aR,8ζ,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 (−)‐(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 β‐equatorial bromine atom and an α‐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 α‐axial bromine atom and a β‐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%. Chirality 21:E208–E214, 2009. © 2009 Wiley‐Liss, Inc.