Revisiting the racemization mechanism of helicenes

Abstract

Herein we propose a general mechanism for the racemization of [n]helicenes up to n = 24. It is a concerted process for n = 4-7, but a multi-step mechanism is followed for n≥ 8, involving 2n- 14 intermediates. The changes in the barriers are a delicate consequence of the steric hindrance and the π-interactions.

Substituent‐Controlled and Rhodium‐Catalyzed Intramolecular [2+2+2] and [2+1+2+1] Cycloadditions of Electron‐Deficient Triynes

“…Additionally, as racemization of an unsubstituted carbo[7]helicene does not proceed at 80 °C, the helicity stability of the above dibenzo[7]helicenes 2 is markedly lower than that of the unsubstituted carbo[7]helicene. This instability may arise from low aromaticity of the two benzene rings in the middle of the two triphenylene skeletons, which may allow flexible bending of two terminal phenanthrene moieties to form the parallel transition state in the racemization process …”

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…Evidently, understanding the mechanism of racemization helps in designing more stable helicene structures. Recently, detailed theoretical racemization studies have been performed on [n]helicenes where n = 4-24 [113]. Consequently, it was found that n = 4-7 involves the one-step concerted mechanism of racemization.…”

Synthesis of Heterohelicenes by a Catalytic Multi‐Component Povarov Reaction

“…Their racemization rate constants were obtained by HPLC following the decay of the enantiomeric excess of the pure enantiomers dissolved in decalin, at temperatures in the range 70 °C–100 °C for 5fc and 5fd and 130 °C–150 °C for 5fb . The associated free energy barriers of enantiomerization are Δ G ‡ = 27.9 kcal/mol and Δ G ‡ = 27.8 kcal/mol for 5fc and 5fd , respectively, whereas a larger free energy barrier Δ G ‡ = 33.6 kcal/mol was found for 5fb . Several examples of enantio‐controlled Povarov reactions are available in literature,[6b] however, the low enantiomerization barriers measured for helical shaped derivatives 5 , but 5fb , and their (partial) formation under the optimized reaction conditions (methods A and B ), vanished the possibility to control the absolute stereochemistry at imine‐dienophile cycloaddition level.…”

“…This behaviour could be due to either fast on‐column enantiomer interconversion or to the absence of enantioselectivity, or to both factors. However, given the large enantioselectivity observed for the parent [5]helicenes and considering the known stereochemical instability of [4]helicene, fast interconversion is more likely responsible for the observed HPLC behaviour. [6]Azahelicene 5fb and [6]azaoxahelicenes 5fc and 5fd , on the other hand, were easily resolved by HPLC at room temperature and gave no evidence of on‐column enantiomer interconversion even when the temperature was raised to 55 °C.…”