Analysis of Interconversion between Atropisomers of Chiral Substituted 9,9’‐Bicarbazole

Abstract

Interconversion of atropisomers of chiral 3,3’‐di‐tert‐butyl‐9,9’‐bicarbazole linked by a single N−N bond was analyzed by DFT calculations and experiments. The calculations revealed that the trans transition state has a lower energy for the interconversion than the cis transition state. The lowest transition state of interconversion between natural dixiamycins A and B containing a 9,9’‐bicarbazole structure was found to be the trans transition state. The calculations also indicated that degradation through N−N bond cleavage was faster than racemization. Atropisomeric enantiomers of 3,3’‐di‐tert‐butyl‐9,9’‐bicarbazole were resolved by chiral HPLC for the first time, and then racemization and N−N bond cleavage were investigated by heating experiments, showing that racemization did not take place below the degradation temperature.

Enantioselective Synthesis of Nitrogen–Nitrogen Biaryl Atropisomers via Copper-Catalyzed Friedel–Crafts Alkylation Reaction

“…All these compounds exhibited good configurational stability, and racemization was not observed after 24 h at either temperature. Degradation was observed at 140 °C for all three compounds, and the amount was reduced to 81% ( 3a ), 10% ( 7a ), and 65% ( 7c ) after 24 h. These results are consistent with Higashibayashi and co-worker’s report that the racemization energy is higher than the degradation energy …”

“…Degradation was observed at 140 °C for all three compounds, and the amount was reduced to 81% (3a), 10% (7a), and 65% (7c) after 24 h. These results are consistent with Higashibayashi and coworker's report that the racemization energy is higher than the degradation energy. 13 A plausible catalytic cycle leading to the observed stereochemical outcome is illustrated in Scheme 3 on the basis of the experimental results and reported work. 17…”

“…Cirilli and co-workers achieved N–N biaryl atropisomers with C 2 symmetry benzimidazole fragments by HPLC resolution . More recently, Higashibayashi and co-workers resolved atropisomeric enantiomers composed of 3,3′-di- tert -butyl-9,9′-bicarbazole by chiral HPLC and investigated racemization of the N–N bond by heating experiments, showing that racemization does not take place below the degradation temperature . However, the atroposelective construction of axially chiral N–N atropoisomers remains unexplored, and the development of facile and direct routes is highly appealing.…”

“…12 More recently, Higashibayashi and co-workers resolved atropisomeric enantiomers composed of 3,3′-di-tert-butyl-9,9′-bicarbazole by chiral HPLC and investigated racemization of the N−N bond by heating experiments, showing that racemization does not take place below the degradation temperature. 13 However, the atroposelective construction of axially chiral N−N atropoisomers remains unexplored, and the development of facile and direct routes is highly appealing. Herein, we describe studies that have led to the first catalytic atroposelective synthesis of N−N axially chiral structures by enantioselective desymmetrization of pyrroles (Scheme 1D).…”

Cross-dehydrogenative N–N couplings

“…Finally, the increasing availability of methods to access these scaffolds might eventually enable atroposelective (dehydrogenative) N–N bond forming methods, analogous to the currently emerging atroposelective C–C 38 and C–N 39 bond forming reactions ( Scheme 22 ). The idea is certainly challenging, 40 but will probably be successful soon in view of the recent progress in atroposelective coupling reactions. 38,39 The general importance of the N-atom in organic chemistry suggests that these methods and their products will be uniquely useful.…”