Circular Dichroism and TDDFT Investigation of Chiral Fluorinated Aryl Benzyl Sulfoxides

Abstract

A series of ten chiral aryl benzyl sulfoxides with perfluorinated aryl or benzyl rings, obtained by enantioselective oxidation of sulfides, has been investigated by means of electronic circular dichroism (ECD) spectroscopy and time-dependent DFT (TDDFT) calculations. The (per)fluorination of the aromatic rings has a large impact on the conformer population, the molecular orbitals shape, and the character of electronic transitions. In this series, the transition responsible for the “sulfoxide primary” CD band has a large charge transfer (CT) character, as demonstrated by the CT metric index ΓNTO. As a consequence, global DFT hybrids such as B3LYP are largely inaccurate in the prediction of excited states; nevertheless, a correct simulation of CD spectra may be achieved by using range-separated functionals such as CAM-B3LYP. The use of the empirical Mislow's rule for assigning the absolute configuration is strongly discouraged for this class of compounds

Good Computational Practice in the Assignment of Absolute Configurations by TDDFT Calculations of ECD Spectra

“…Several recent reports demonstrate that range‐separated functionals like CAM‐B3LYP and ωB97X‐D are superior to hybrid functionals, first of all B3LYP, in the prediction of chiroptical properties . A good example is offered by sulfoxide 5 (Fig.…”

“…A good example is offered by sulfoxide 5 (Fig. ), for which CAM‐B3LYP and ωB97X‐D were able to predict the correct sequence of ECD bands, while B3LYP was not, particularly because of a severe underestimation of the energy of the first band . When such a situation occurs, a deeper analysis of transitions and orbitals is desirable to uncover a possible specific functional‐related issue.…”

Stereochemical analysis of β‐keto sulfoxides by circular dichroism

“…In the next step of our stereochemical analysis, simulations of the ECD spectra for 1 to 3 were carried out using the TDDFT method at the CAM‐B3LYP/def2‐TZVP level of theory in PCM for CH 3 CN, which was recommended in our previous work for calculations of sulfoxides and similar molecules . The comparison of the experimental and computed ECD spectra is presented in Figure .…”

“…The choice of these molecules was further motivated by the wish of comparing chiroptical properties of non‐fluorinated sulfoxide 1 with monofluorinated and pentafluorinated sulfoxides 2 and 3 . It is well known that the replacement of hydrogen atom(s) by fluorine(s) may strongly affect various molecular properties, including chiroptical ones . Thus, performing such study will allow us to better understand the impact of the fluorine substitution on electronic and vibration chiroptical properties of the titled class of compounds.…”

Synthesis, Separation and Absolute Configuration Determination by ECD Spectroscopy and TDDFT Calculations of 3‐Amino‐β‐lactams and Derived Guanidines

“…In particular, the O= C-N-C4 dihedral angle, which is given primary importance in the aforementioned helicity rule, [26] was negative for the most stable conformers of 4a and 5a, and positive for those of 4c (Table 2). [20,35,36] Our first choice for TDDFT calculations of -lactams was therefore CAM-B3LYP, especially because the aromatic groups present in 4, 5, and 9 are expected to yield transitions with some chargetransfer character. When checked against the actual values calculated for the O=C-N-C4 dihedral angles, [26,27] the helicity rule fails for 4a and 5a, and holds only for 4c (Table 2).…”