A Critical Appraisal of Dimolybdenum Tetraacetate Application in Stereochemical Studies of vic-Diols by Circular Dichroism

Abstract

This critical appraisal is intended for users of the dimolybdenum method, well-established in electronic circular dichroism (ECD) to determine the absolute configuration of vic-diols and, in particular, for experimental researchers not being experts in chiroptical methods. The main goal is to demonstrate how to avoid misleading and ambiguous conclusions resulting from the rigorous application of the helicity rule by limiting the analysis to the vic-diol unit alone. We particularly focused on multichromophoric systems, especially those that may interfere with the absorption of an in situ formed dimolybdenum tetraacetate-diol complex. In this context, examples are presented of vic-diols for which stereochemical assignment based solely on the helicity rule is ambiguous and does not necessarily lead to correct results. The motivation for choosing these examples was to demonstrate the impact of the structure of the substrate on the complexation process with the metal core and its selectivity. For each selected case, results obtained are analyzed in detail together with a discussion of existing restrictions and choice of a support method to increase the credibility of the conclusion. Based on seven both educational and challenging examples, it was shown that the dimolybdenum methodology can also be effectively applied to complex chromophoric systems, provided that other chiroptical methods and/or computational support verify obtained results.

A Holistic Approach to Determining Stereochemistry of Potential Pharmaceuticals by Circular Dichroism with β-Lactams as Test Cases

“…On the other hand, transforming the tert/tert 1,2-diol subunit present in 10 into an ECD-active cottonogenic derivative is not straightforward. Another solution to this problem offers the so-called in situ dimolybdenum method [ 23 , 64 , 65 , 66 ]. This simple, fast, and yet reliable method is highly effective for both flexible and sterically demanding vic -diols, including tert/tert vic -ones.…”

“…Despite the empirical nature of the method, its great advantage is a transformation of labile systems into almost rigid and, above all, conformationally defined derivatives. Ligating the flexible diol molecule to the Mo2-core causes a significant reduction in the diol’s internal conformational mobility due to the stock complex’s steric requirements [ 64 , 65 ]. As a result, in most cases, the molecule appears to exist as a single conformer with an antiperiplanar orientation of both O-C-C-R units only.…”

Stereochemistry of Chiral 2-Substituted Chromanes: Twist of the Dihydropyran Ring and Specific Optical Rotation

“…The theoretical SORs for compounds 66 and 67 calculated using the BL approach in methanol were +128.1 and −129.8, respectively, concordant with the SOR sign predicted based on the correlation. The AC of compound 67 was further inspected by Snatzke's method and ECD calculations [71][72][73][74][75][76][77][78][79][80][81]. The positive CE sign at approximately 310 nm verified its (R,R)-configuration.…”

Two New Enantiomers of Phenylethanoid and Their Anti‐Inflammatory Activities

“…In this study, twelve compounds were isolated from the leaves of P. quassioides including two pairs of new phenylethanoid derivative enantiomers ( 1a / 1b and 2a/2b ), a new phenylethanoid derivative 3b , and seven known compounds ( 3a , 4 – 9 ) ( Figure 1). Snatzke's method [18,19] was used to identify the absolute configurations of these compounds. Besides, we evaluated their ( 1a/1b – 3a/3b ) effect on NO production using lipopolysaccharide (LPS)‐stimulated BV2 cells [20–25] …”