Determination of the absolute configuration of bicyclo[3.3.1]nonane‐2,7‐dione by circular dichroism spectroscopy and chemical correlation

Abstract

A study of the enantiomers of bicyclo[3.3.1]nonane-2,7-dione, a chiral molecule containing two carbonyl chromophores, was performed. Enantiomers of this structure were obtained by HPLC resolution and the (+)-(1R,5S)-enantiomer by enantiospecific synthesis from(+)-(1S,5S)-bicyclo[3.3.1]nonane-2,6-dione. The title structure is an interesting molecule to demonstrate the validity of the octant rule. The location of the major chair-chair conformer into octants placing each chromophore into the origin of the octants led to the opposite configuration assignments. In order to prove unequivocally absolute configuration, enantiospecific synthesis of the title compound was carried out. The kinetic resolution of racemic bicyclo[3.3.1]nonane-2,6-dione using baker's yeast afforded (+)-(1S,5S)-2,6-dione. Employing a reaction sequence analogous to one developed earlier by us with racemic substrates led to carbonyl group shift giving enantiomerically pure (+)-(1R,5S)-bicyclo[3.3.1]nonane-2,7-dione. The absolute configuration of the investigated compound was established by combined use of the octant rule and chemical correlation.

Vibrational Circular Dichroism Detects Symmetry Breaking due to Conformational Mobility in C2-Symmetry Chiral Molecules and Provides Further Insight into Inter-Chromophoric Interactions

“…The syntheses and characterization of compounds 1 and 2 are described in References [1][2][3][4][5][6]. VCD measurements were run on a Jasco FVS6000 instrument, utilizing an MCT detector for the region 850-2000 cm −1 and an InSb detector for 2700-3200 cm −1 ; spectra were taken for concentration values in the range 0.02-0.05 M in CCl 4 solvent, and 5000 scans were collected and averaged.…”

“…As pointed out above, the conformational aspect is essential for understanding the VCD spectra. A theoretical analysis had been already reported in References [2,[4][5][6]23]; the last study had been conducted by comparing different levels of calculations in order to account for the observed ECD spectrum (see below). In particular, two main conformers, cc and cb, have been indicated.…”

“…To describe the interplay of carbonyl and diene moieties in modulating chiroptical response, we re-examine here the UV and ECD spectra of 1 and 2, previously reported in References [1][2][3][4][5][6] (Figure 4). Both are diketones, and their differences and characteristics are indeed largely determined by the absence or presence of the C=C moieties.…”

“…Bicyclo [3.3.1]nonane-2,6-dione (1) and bicyclo [3.3.1]nona-3,7-diene-2,6-dione (2) in Scheme 1 was synthesized earlier and studied [1][2][3][4][5][6] to learn whether and to what extent electron delocalization through homo-conjugation and transannular interactions, defined by Hoffman et al [7], manifest in the characteristics of a "coupled" chromophore [8][9][10]. Evidence was provided by 13 C-NMR chemical shift δ(C=O), photoelectron spectroscopic data [1], as well as electronic circular dichroism (ECD) data [2].…”

Crystallisation of C2-symmetric endo,endo-bicyclo[3.3.1]nonane-2-6-diols: supramolecular synthons and concomitant degrees of enantiomer separation

“…In this case, the slower reacting isomer is (+)-3, which can be obtained in 24% yield (93% ee), commencing with 3.0 g of racemic material. 20,21 Samples of 3 resolved by these methods have been utilised in syntheses of enantiopure methanocycloocta[b]indoles, 19 twistbrendanedione, 21 bicyclo[3.3.1]nonane-2,7-dione, 22 2,6-diaminobicyclo[3.3.1]nonane, 23 and other chiroptically fascinating molecules.…”