Macromolecular Helicity Induction and Memory in a Poly(biphenylylacetylene) Bearing an Ester Group and Its Application to a Chiral Stationary Phase for High-performance Liquid Chromatography

Abstract

An optically inactive poly(biphenylylacetylene) bearing an ester group at the 4¤-position of the pendants formed a preferredhanded helical conformation and biased axial chirality in the pendants through a noncovalent interaction with a chiral alcohol, both of which were retained (memorized) even after removal of the chiral alcohol. The chiral stationary phase for high-performance liquid chromatography, prepared by coating the polymer with macromolecular helicity memory on silica gel, showed good chiral recognition ability towards various racemates.Direct enantioseparation, using chiral stationary phases (CSPs), by high-performance liquid chromatography (HPLC) has provided a promising method not only for performing microanalysis of chiral compounds but also for obtaining highly-pure enantiomers on the ton scale.1,2 Although a large number of CSPs have been developed, 3,4 it is still a challenging issue to switch the elution order of enantiomers without using the CSPs prepared from antipodal chiral materials despite their advantages both in analytical and preparative modes. 5,6 We recently reported that poly([2,2¤-bis(methoxymethoxy)-4¤-dodecyloxy-4-biphenylyl]acetylene) (poly(DOBA)) forms a preferred-handed helical conformation together with an excess of one of the axially twisted conformations in the biphenyl pendants, which occurs through the noncovalent interaction with an optically active alcohol ((R)-or (S)-1) both in solution and in the solid state. 7 The induced main-chain helicity and axial chirality can be maintained (or memorized) even after the removal of the chiral alcohol (Scheme 1). By using this unusual feature of poly(DOBA), we succeeded in developing a switchable CSP in which the elution order of the enantiomers could be switched at will on the basis of reversible switching and the subsequent memory of macromolecular helicity in poly(DOBA) by sequential treatment with (R)-and (S)-1 in the solid state.However, the chiral recognition ability of poly(DOBA) was not high. In this communication, we designed and synthesized a novel cis-transoidal poly(biphenylylacetylene) derivative bearing an ester group as an effective chiral recognition site instead of an ether group, poly([2,2¤-bis(methoxymethoxy)-4¤-butoxycarbonyl-4-biphenylyl]acetylene) (poly(BCBA)) (Scheme 1), and investigated the effects of the functional group at the 4¤-position of the biphenyl pendant on helicity induction and memory effect, and further the chiral recognition ability as a CSP for HPLC.Poly(BCBA) was synthesized by the polymerization of the corresponding biphenylylacetylene monomer (Scheme S1) with a rhodium catalyst ([Rh(nbd)Cl] 2 ; nbd: norbornadiene) in tetrahydrofuran in the presence of triethylamine in a similar method to that previously reported (Scheme S2).7 The stereoregularity of the obtained polymer was confirmed to be almost completely cis-transoidal by 1

Chromatographic enantioseparation by poly(biphenylylacetylene) derivatives with memory of both axial chirality and macromolecular helicity

“…Although poly‐ Ac‐c exhibited strong ICDs in n ‐hexane and MCH, the ICD intensity significantly decreased in toluene and no detectable ICD signal was observed in THF and chloroform (Figure S12), probably due to very weak interactions between the poly‐ Ac‐c and the chiral alcohol 1 in these solvents. A similar tendency was also observed for the poly‐ MOM 's . Since poly‐ Ac‐b is insoluble in MCH and n ‐hexane, but soluble in 1 , we then measured the CD spectrum of poly‐ Ac‐b in ( R )‐ 1 , which showed intense, but slightly weak Cotton effects (Figure (v)) when compared to those of poly‐ Ac‐c , indicating a preferred‐handed helix formation of poly‐ Ac‐b in ( R )‐ 1 whose helix‐sense excess may be slightly lower than that of poly‐ Ac‐c .…”

“…The isolated poly‐ Ac‐c dissolved in MCH at −10 °C showed an almost identical CD spectrum to that observed before isolation (Figure (ii) and (iii)). Therefore, it was revealed that a preferred‐handed helicity induced in poly‐ Ac‐c was retained after complete removal of ( R )‐ 1, as is the case for the poly‐ MOM 's . The stability of the helicity memory of the poly‐ Ac‐c was investigated by following the CD intensity changes in MCH at −10 and 25 °C with time; its half‐life periods ( t 1/2 ) were estimated to be ~24 h and 10 min, respectively (Figure ) .…”

“…Therefore, the helicity induction and memory effect were investigated in detail for poly‐ Ac‐c in MCH, whereas poly‐ Ac‐b with a helicity memory was used to prepare a coated‐type CSP for HPLC and its chiral recognition ability was examined under normal phase conditions toward various racemates because poly‐ Ac‐c is readily soluble in eluents under normal phase conditions and its chiral resolving ability as a coated‐type CSP could not be evaluated. For comparison, poly‐ MOM‐c bearing MOM groups at the 2‐ and 2′‐positions and an n ‐dodecyloxycarbonyl group at the 4′‐position of the biphenyl residue, which was soluble in MCH, was also prepared because the previously reported poly‐ MOM‐b was insoluble in MCH (Scheme S2 and Table S1) …”

Synthesis of Optically Active Poly(diphenylacetylene)s Using Polymer Reactions and an Evaluation of Their Chiral Recognition Abilities as Chiral Stationary Phases for HPLC

“…Ultraviolet (UV) and polarimetric (PM) detectors were used for the detection and identification of the peaks, respectively. As shown in Figure 7c, the different enantiomers of 16 were eluted with retention times of t1 ((-)-enantiomer) and t2 ((+)-enantiomer), The chiral recognition abilities of poly-2S, h-poly-2S and h-poly-(2S 0.36 -co-3 0.64 ) as CSPs for HPLC were evaluated using the various racemic compounds with different functional groups (5-12) including axial (13,14) or planar (15) chiral compounds as well as chiral metal complexes (16)(17)(18) (Figure 6). The packing materials were prepared by coating macroporous silica gel (particle size 7 µm, pore size 100 nm) with DMF solutions of the corresponding polymers [49].…”

“…Optically active poly(phenylacetylene)s with a preferred-handed helicity have been prepared [16] and some of these systems have been reported to exhibit good chiral recognition abilities as CSPs for HPLC because of their preferred-handed helical conformation [17][18][19][20][21][22][23][24][25][26]. However, very few optically active poly(diphenylacetylene)s have been prepared to date, which has limited research towards evaluating the scope and efficiency of the chiral recognition abilities of these materials [27][28][29][30][31][32][33][34][35].…”