Resolution of a configurationally stable [5]helquat: enantiocomposition analysis of a helicene congener by capillary electrophoresis

Abstract

Racemic [5]helquat as a triflate salt has been synthesized using a robust, three-step procedure. Subsequent exchange of triflate anions for inexpensive (R,R)-dibenzoyltartrate anions via an ion exchange resin afforded two diastereoisomeric salts. Crystallization led to the resolution of the helquat (ee 4 98%). This is the first time that a non-racemic helquat has been obtained; its helicity having been assigned and its racemization barrier determined. Capillary electrophoresis with a sulfated b-cyclodextrin chiral selector is introduced for the first time as a straightforward method to analyze the enantiocomposition of charged, helicene-like species.

Preferential Crystallization of a Helicene–Viologen Hybrid – An Efficient Method to Resolve [5]Helquat Enantiomers on a 20 g Scale

“…[18] This resolution gave enantiopure [P-1][TfO] 2 in milligram quantities. During our studies on helquats, [12,18] we realized that the preparative power of PC to separate enantiomers of helical aromatics in multigram quantities is attractive and remains unexplored. Because of this, we became interested in the demonstration of the mass throughput advantage of this method with our helicene-viologen hybrids such as [1][TfO] 2 .…”

“…To this end, we started with slightly enantiomerically enriched [1][TfO] 2 (100 mg, 7.6 % ee in favor of the P enantiomer) and attempted PC with seeds of enantiopure (+)-[P-1]-[TfO] 2 (0.7 mg), which was obtained by our dibenzoyltartrate resolution route. [18] Solids collected from this crystallization experiment (15 mg) had an ee value of over 85 %, which showed that [1][TfO] 2 indeed forms a conglomerate. With this information in hand, we went on to develop a PC protocol for 1 on a 10 g scale.…”

“…In contrast to our published resolution procedure, [18] this optimized resolution protocol avoids the time-consuming solvent-diffusion step to separate the [P-1]-[(R,R)-dibenzoyl tartrate] 2 diastereomer from the mixture of the two diastereomeric salts and uses fast and simple sonication of the suspension of the diastereomeric salts mixture in methanol instead (Scheme 2, Step 2). In addition, this new protocol does not require the use of ionexchange resin in the final ion-exchange step, 2 with an ethereal solution of TfOH led to complete conversion to [P-1][TfO] 2 (Step 3).…”

“…[25] The P helicity was in agreement with the absolute configuration assignment based on the electronic circular dichroism (ECD) spectrum, which was complemented by simulations at the TDDFT/BMK/TZVP level using the RI-DFTD/B3LYP/TZVP geometries. [18] Figure 6. X-ray crystal structure of (+)- [P-1][TfO] 2 , which confirms P configuration.…”

“…[21,18] Recently, CE with a randomly sulfated β-cyclodextrin chiral selector has been shown to be an advan- tageous and direct method for analysis of enantiocomposition of this helical dication. [18] Enantiocomposition analysis by CE introduced here represents an optimized analytical protocol using a sulfated β-cyclodextrin chiral selector as a single isomer [heptakis- (2,3-…”