Systematic Investigation of CD Spectra of Aryl Benzyl Sulfoxides Interpreted by Means of TDDFT Calculations

Abstract

The CD spectra of 13 crystalline aryl benzyl sulfoxides 1a-m with various substituents on the two aromatic rings were recorded in solution and in the solid state. Solution CD spectra were very homogeneous along the series, consisting in most cases of a couplet-like feature in the 200-300 nm region. The red-shifted component of the couplet, corresponding to the sulfoxide-centered n-pi* transition, is always positive for (R) absolute configuration in accordance with Mislow's rule. The presence of a strong electron-withdrawing substituent on the phenyl ring (nitro or ester group) alters the shape of the CD spectrum. CD calculations using the TDDFT method were run for eight representative compounds using DFT-optimized geometries. In all cases, calculated spectra were in very good agreement with experimental ones and allowed for rationalization of the diverse spectral behaviors. It is demonstrated that TDDFT//DFT calculations represent a reliable option for assigning the absolute configuration of this class of compounds whenever crystals suitable for X-ray are not available. Solid-state CD spectra recorded with the KCl pellet technique were in some cases in agreement with those in solution. However, in other cases new and strong CD signals appeared which were interpreted as being due to intermolecular couplings in the crystals.

A Study of Factors Affecting Enantioselectivity in the Oxidation of Aryl Benzyl Sulfides in the Presence of Chiral Titanium Catalysts

“…The first CD spectrum of (R)-benzyl p-tolyl sulfoxide was recorded by Stirling, [30] and a similar pattern was reported by Mislow et al [31] for (R)-alkyl aryl sulfoxides. In our recent experimental and theoretical work on (R)-aryl benzyl sulfoxides, [32] we found the same pattern reported in the literature, [30][31] i.e., a moderately intense positive band around 250-260 nm and a negative band around 220-230 nm. [32] The most significant dif- ferences were observed when electron-withdrawing groups or substituents in the ortho-position irrespective of their electronic effect were present on the phenyl group.…”

“…In our recent experimental and theoretical work on (R)-aryl benzyl sulfoxides, [32] we found the same pattern reported in the literature, [30][31] i.e., a moderately intense positive band around 250-260 nm and a negative band around 220-230 nm. [32] The most significant dif- ferences were observed when electron-withdrawing groups or substituents in the ortho-position irrespective of their electronic effect were present on the phenyl group. [32] However, by performing TDDFT calculations, we have been able to make a full and fairly accurate prediction of all the CD spectra of the (R)-aryl benzyl sulfoxides.…”

“…Because the patterns of these CD spectra are expected both from experimental [30,31] and theoretical points of view [32] for sulfoxides having the (R)-configuration, [30][31][32] this configuration could also be assigned to compounds 2b-7b and 9b-10b.…”

“…[32] However, by performing TDDFT calculations, we have been able to make a full and fairly accurate prediction of all the CD spectra of the (R)-aryl benzyl sulfoxides. [32] On the basis of these predictions, and also taking into account all the reported CD spectra of the (R)-alkyl aryl sulfoxides, [30][31] the attribution of configuration of the aryl benzyl sulfoxides and related molecules by CD spectra can now be considered safe.…”

Circular Dichroism and TDDFT Investigation of Chiral Fluorinated Aryl Benzyl Sulfoxides

“…[12,13] In recent years, we have been studying aromatic sulfoxides from several different viewpoints, including their enantioselective synthesis, [14][15][16] crystal structure determination, [14,17] and chiroptical characterization. [15,18,19] This interest is justified by the synthetic value of enantiopure sulfoxides employed as auxiliaries and intermediates in stereoselective synthesis, [20] as well as by the biological and medicinal importance of some chiral sulfoxides. [21] In particular, some of us developed an efficient synthetic procedure based on the tert-butyl hydroperoxide (TBHP) mediated enantioselective oxidation of the corresponding sulfides in the presence of a complex between titanium tetraisopropoxide and commercially available hydrobenzoin.…”