In 1955 Mislow1 discussed the possibility of enatiomers interchanging via a path that was entirely chiral, never passing through an achiral structure. His analogy is the inversion of a rubber glove, taking a right hand rubber glove and pulling it inside out creates a left hand glove (its mirror image) but never passing through an achiral glove. Well, now a helicene with this type of stereochemistry has been developed, with a stable chiral intermediate.2

Helicenes typically interchange (PMP) through an achiral saddle-like structure. But larger helicenes can have high-lying intermediates along this pathway. Helquat P-1 interchanges to M-1 through the intermediate 2, which is an achiral structure and can be isolated.

Computations at B3LYP/def2-TZVP//PBE/def2-SV(P) with dispersion corrections (and PCM simulating DMSO) of the inversion process identified a number of intermediates and transition states along the stereoinversion pathway. The intermediate 2 lies 18.4 kJ mol-1 above 1. These structures are shown in Figure 1. The highest lying TS between 2 and P-1 (labeled TSP in Figure 1) is 119 kJ mol-1 above 2. The highest lying TS on the path from 2 to M-1 (labeled TSM in Figure 1) is 138 kJ mol-1 above 2. Note that going from 2 to P-1 is not the mirror image path of going from 2 to M-1.






Figure 1. Optimized structures of 1, 2, and the highest transition states interconverting them.

Heating racemic 2 and following the conversion to 1 with NMR gives the activation barrier of 119 kJ mol-1, in excellent agreement with the computation.

Racemic 2 was resolved through differential crystallization and its x-ray structure indicates it is (+)-[Sa,Ra]. Heating it does give just P-1, as predicted by the computations. Then heating P-1 to 180 °C does racemize it, with an experimental barrier of 157.7 kJ mol-1. The computations predict a barrier of 156.6 kJ mol-1, again in fine agreement with experiment. Overall, a nice piece showing experiment and computation working together to provide an understanding of an interesting chemical system!


(1) Mislow, K.; Bolstad, R., "Molecular Dissymmetry and Optical Inactivity," J. Am. Chem. Soc., 1955, 77, 6712-6713, DOI: 10.1021/ja01629a131

(2) Adriaenssens, L.; Severa, L.; Koval, D.; Cisarova, I.; Belmonte, M. M.; Escudero-Adan, E. C.; Novotna, P.; Sazelova, P.; Vavra, J.; Pohl, R.; Saman, D.; Urbanova, M.; Kasicka, V.; Teply, F., "[6]Saddlequat: a [6]helquat captured on its racemization pathway," Chem. Sci. 2011, ASAP, DOI: 10.1039/C1SC00468A


1: InChI=1/C27H26N2/c1-2-11-23-20(8-1)15-19-29-18-7-10-22-14-13-21-9-3-5-16-28-17-6-4-12-24(28)25(21)26(22)27(23)29/h1-2,4,6,8,11-15,17,19H,3,5,7,9-10,16,18H2/q+2