Conformational Analysis of δ‐Lactones by DFT Calculations: The Parent Compound and its Monomethyl and Selected Dimethyl Derivatives

Abstract

The static and dynamic stereochemistry of unsubstituted δ-valerolactone, all monomethylated δ-lactones, and all nongeminally dimethylated δ-lactones was explored with the B3LYP functional and def2-TZVPP basis set. A search strategy was employed which allowed the entire conformational space of any (poly-)substituted δ-lactone to be scanned. It allowed the lowest threshold conformational interconversion pathways to be mapped. The latter can be visualized in appealingly intuitive yet unprecedented diagrams. They trace the energy versus a circular abscissa which describes the passage of the molecule through one complete conformation interchange. The respective plot is C(2)-symmetrical for the parent compound, which is achiral, and C(1)-symmetrical for all methylated δ-lactones, which are chiral.

Quantification of the Nucleophilic Reactivities of Cyclic β‐Keto Ester Anions

“…The same argument that has been employed to rationalize the higher acidity of dimedone (p K a = 11.2)3f compared with pentane‐2,4‐dione (p K a = 13.3)3f may apply. Only the anion of dimedone can adopt the W‐configuration with optimal charge distribution, whereas steric interactions of the methyl groups hinder the formation of a W‐shaped anion from pentane‐2,4‐dione and thus account for its lower acidity 15,16. Given that the constitution of 4 also prevents the formation of an anion with W‐configuration, its higher basicity (compared with that of 3 ) and, as a consequence, higher nucleophilicity, can be explained.…”

(−)‐R‐Mevalonolactone Studied by ROA and SERS Spectroscopy

“…Most of the literature is devoted to the analysis of the conformations of unsubstituted δ‐lactones, i.e., δ‐valerolactone. Its conformation was explored both experimentally by 1 H NMR, 13 C NMR, and Raman spectroscopy, and theoretically by MM2, MM3, HF/6‐31G*, MP2 or G3 MP2, and B3LYP methods with different basis sets . All of these calculated data match the experimental one very well, and show that δ‐valerolactone exists in half‐chair and a little less stable as boat conformations.…”

“…For example, the δ‐valerolactone with the methoxy substituent in the same position in the six‐membered ring like substituents in the (−)‐R‐mevalonolactone molecule take chair, half‐chair, skew, and boat conformations . On the other hand, the calculations show that the compound with the methyl group in the same place exist in half‐chair and boat conformations only …”

Combined Experimental and Theoretical Study of the Reactivity of γ-Butyro- and Related Lactones, with the OH Radical at Room Temperature

“…An exhaustive investigation of the conformational structure of δ-valerolactone or DVL has been carried out by Weber and Brückner at the B3LYP/def2-TZVPP level. In addition they summarize many previous studies and conclude that a half-chair form is the most stable structure which faces an inversion barrier of some 12 kJ mol –1 .…”