Determination of Absolute Configurations of N-Formyl-3,3‘,4,4‘-tetrahydrospiro[naphthalene-1(2H),2‘(1‘H)-pyridine] (2) and N-Formyl-3‘,4‘-dihydrospiro[indan-1,2‘(1‘H)-pyridine] (3) by Analysis of Circular Dichroism Spectra. A Case of Two Compounds with Similar Configuration But Nearly Mirror Image CD Spectra

Abstract

N-Formyl-3,3‘,4,4‘-tetrahydrospiro[naphthalene-1(2H),2‘(1‘H)-pyridine] (2) and N-Formyl-3‘,4‘-dihydrospiro[indan-1,2‘(1‘H)-pyridine] (3) were resolved into enantiomers, compound 3 partly and compound 2 completely, by chromatography on triacetylcellulose. The CD spectra were recorded and compared with theoretical spectra calculated by a semiempirical method, using geometries from empirical force-field calculations. In the observed CD spectra, the carbonyl n → π* transitions did not give rise to visible bands, but their signs and energies were found by analysis of CD spectra in solvents of different polarity. The theoretical spectra of 2 and 3 showed complete agreement with the observed spectra in sign and qualitatively in intensity, for the five transitions observed between 190 and 280 nm, which permitted a safe assignment of the absolute configurations. The enantiomers of 2 and 3 with the aryl rings located on the same side of the tetrahydropyridine ring showed CD spectra, which were nearly mirror images, thus demonstrating the risk of deducing absolute configurations by a direct comparison of CD spectra.

Application of electronic circular dichroism in configurational and conformational analysis of organic compounds

“…4 provide another remarkable example. 15 They contain the same chromophores, but the 5-or 6-membered rings adopt different conformations which reflect into quasi-mirror image CD spectra for the same Fig. 4 CD spectra of two apparently very similar compounds (adapted from ref.…”

“…4 CD spectra of two apparently very similar compounds (adapted from ref. 15, with permission; copyright 1997 American Chemical Society): notice that actually the absolute stereochemistry is identical (even though, according to the sequence rules (see the numbering), 4a is (1R), 4b is (1S)). Bottom structures show the different conformation adopted by the two compounds.…”

“…4) were predicted by considering four aromatic transitions ( 1 B a,b and 1 L a,b ), the enamide p-p* transition, and the n-p* carbonyl transition (overall, five electric and one magnetic moment, giving a 666 interaction matrix); the correct absolute configuration of the two compounds was thus assigned. 15 The input for such kind of computations 26 requires: 1) a complete description of each chromophore (transition dipoles energy, strength, direction and position); 2) a known molecular structure, i.e., relative positions and orientations between chromophores. The first set of data can often be found in the literature or evaluated from experimental absorption spectra, and computed by suitable excited-state calculations on the isolated chromophores.…”

How and How Much Molecular Conformation Affects Electronic Circular Dichroism: The Case of 1,1-Diarylcarbinols

“…In a much simpler but very clever and didactic way, a good means of demonstrating the impact of molecular conformation on ECD spectra would consist in finding a pair of compounds with a very similar skeleton and consistent absolute configuration, but showing very different ECD spectra, possibly even the mirror image of each other. A very nice example of this kind was reported in 1997 by Sandström and co-workers concerning two analogous spiro compounds which would show mirror-image ECD spectra for the same configuration at the spiro center, due only to a different cycle size (5- vs. 6-membered) [ 26 ]. Unfortunately, we showed recently that this example is faulty, because one absolute configuration was wrongly assigned [ 27 ].…”

Chemical investigations of endophytic and fungicolous fungi

“…An excellent example is provided by compounds 1.5 and 1.6 ( Figure 1.3). 36 Both compounds contain the same chromophores and have the analogous configuration at the chiral centers (even though the R vs. S assignment is different based on priority rules). Interestingly, however, the two compounds have ECD spectra (Figure 1.3) with opposite signs and opposite shapes because the constraints of the five-and six-membered rings lead to quite different relative orientations of the chromophores, resulting in different conformations for the two compounds.…”