Chemoenzymatic Approach to Optically Active 4‐Hydroxy‐5‐alkylcyclopent‐2‐en‐1‐one Derivatives: An Application of a Combined Circular Dichroism Spectroscopy and DFT Calculations to Assignment of Absolute Configuration

Abstract

A series of representative optically active derivatives of 4-hydroxy-5-alkylcyclopent-2-en-1-one were prepared from the respective 2-furyl methyl carbinols via the Piancatelli rearrangement followed by the enzymatic kinetic resolution of racemates. Applicability of chiroptical methods (experimental and calculated electronic circular dichroism [ECD] and vibrational circular dichroism [VCD] spectra) to determine the absolute configuration of both stereogenic centers in 4-hydroxy-5-methylcyclopent-2-en-1-one was demonstrated. It was also demonstrated that the concurrent application of ECD and VCD spectroscopy can be used for the determination of the configuration of two stereogenic centers.

Dolabellane and Clerodane Diterpenoids from the Twigs and Leaves of Casearia kurzii

“…The absolute configurations of 1a and 1b were assigned by analysis of the ECD spectra. The ECD spectrum of 1a, the second eluting enantiomer in HPLC, showed similar Cotton effects to those reported for (4S)-4-hydroxy-5-alkylcyclopent-2-en-1-one derivatives, 23,24 with a positive Cotton effect at 230 nm (π → π* electronic transition of an enone moiety) and a negative one at 320 nm (n → π* transition of an enone unit), suggesting the same (11S) absolute configuration of 1a. By comparison of the experimental and calculated ECD curves (Figure 3), the absolute configuration of 1a was confirmed.…”

Synthesis and Comprehensive Structural and Chiroptical Characterization of Enones Derived from (−)-α-Santonin by Experiment and Theory

“…Currently, chiroptical methods combined with quantum chemical calculations are considered as the most powerful tools for elucidating stereochemistry and monitoring even the smallest changes in the geometry of chiral molecules. A combined experimental and theoretical analysis of ECD spectra has already proven useful and reliable in the determination of the absolute configuration of various classes of chiral molecules. − …”

Complementarity of electronic and vibrational circular dichroism based on stereochemical studies of vic-diols

“…Very recently, such a combined approach was successful in determining the AC in trolox derivatives [66] and 4-hydroxy-5-methylcyclopent-2-en-1-one [67]. In the chromane chromophore, VCD spectroscopy supported by DFT calculations enabled revision of the AC assignment based on the chromane helicity rule of two compounds isolated from the leaves of Peperomia obtusifolia [68].…”

“…In turn, VCD allowed unambiguous assignment of configuration at C5 carbon atom as being (R), at the same time distinguishing between the diastereoisomers. Consequently, a rapidly developing VCD method complemented ECD, enabling reliable, unambiguous assignment of the AC at both stereogenic centers simultaneously [67].…”