In Depth Analysis of Chiroptical Properties of Enones Derived from Abietic Acid

Abstract

With the use of inexpensive commercially available abietic acid, a whole series of abietane enones were prepared in high yields. The structures of all the products obtained were determined by comprehensive spectroscopic analysis with particular emphasis on the use of advanced NMR techniques, comparison with previously reported data and, where possible, by single crystal X-ray diffraction. However, in cases where X-ray crystallography was not applicable or compounds tested were unstable, a final stereochemical assignment could be inferred only by electronic circular dichroism (ECD) supported by vibrational circular dichroism to increase credibility. To reveal the relationship between structure and chiroptical properties, we used combined experimental and theoretical analysis of geometries, structural parameters, and chiroptical properties of all enones synthesized. A thorough analysis of their conformational flexibility by examining the effect of solvent and temperature on the ECD spectra was also used to achieve desired objectives. As a result, the impact of substituents adjacent to the enone chromophore on the conformation was determined by demonstrating that even slight changes in the position of hydroxyl and isopropyl groups attached to carbon C13 may substantially affect ECD curves' pattern, leading in some cases to Cotton effects sign reversal.

Research into the oxidation of abietic acid–derived enone with atmospheric oxygen

“…The organic layer was dried over Na 2 SO 4 and evaporated to dryness. The residue was chromatographed on silica gel to yield 1.29 g (60%) of ketone 3 with melting point and spectroscopic data consistent with the literature …”

“…An organic layer was dried over sodium sulfate and evaporated to dryness. The residue was chromatographed on silica gel (10% ethyl acetate in hexane) to yield alcohols 6 (108 mg, 23%), 7 (43 mg, 9%), 8 (124 mg, 25%), and 9 (26 mg, 6.0%) with spectroscopic data of 6 to 8 consistent with the literature …”

“…Just the possibility of directing the abietic acid reactions to the desired product, along with its virtually unlimited availability, caused that in our recent studies, we have found it as convenient starting material for the synthesis of model cis ‐enones needed for in‐depth dichroic studies . While the synthesis leading to the entire range of relevant cis ‐enones was simple and consisted of a few steps at most, we encountered problems associated with abietane autoxidation.…”

“…During attempts to convert β,γ‐unsaturated ketone, ie, methyl 7‐oxoabiet‐13(14)‐en‐18‐oate, into its conjugated counterpart under basic conditions, instead of the expected 8(14)‐en‐7‐one derivative, we obtained a mixture of self‐oxidation products depending on the base applied. Hence, a reaction performed in THF in the presence of triethylamine produced diastereomeric 13α‐ and 13β‐hydroperoxides, whereas reaction carried out in toluene in the presence of catalytic amounts of sodium t ‐butoxide yielded a mixture of 13α‐, 13β‐, and 8α‐alcohols in percentage 26:11:34, respectively . Although the expected migration of the C13‐C14 double bond to the C8‐C14 position indeed occurred, it immediately underwent subsequent oxidation at the allylic site by air oxygen to epimeric hydroperoxides or alcohols.…”

“…Hence, a reaction performed in THF in the presence of triethylamine produced diastereomeric 13α‐ and 13β‐hydroperoxides, whereas reaction carried out in toluene in the presence of catalytic amounts of sodium t ‐butoxide yielded a mixture of 13α‐, 13β‐, and 8α‐alcohols in percentage 26:11:34, respectively . Although the expected migration of the C13‐C14 double bond to the C8‐C14 position indeed occurred, it immediately underwent subsequent oxidation at the allylic site by air oxygen to epimeric hydroperoxides or alcohols. Moreover, a reaction carried out in the same conditions but under argon in a strictly deoxygenated mixture of THF and triethylamine yielded the same result, thus proving that air oxidation of the allylic position in 8(14)‐en‐7‐one derivative must be rapid and occurs spontaneously at the workup stage.…”