High-Performance Liquid Chromatographic Resolution of Neutral and Cationic Hetero[6]Helicenes.

Cationic hetero[6]helicenes 1+, 2+ and 3+ have been recently disclosed. Herein we report on their enantiomeric separation using high-performance liquid chromatography. Separation of the antipodes can be achieved in preparative scale on neutral adducts with Chiralcel OD-I or Chiralpak ID CSP. Selectivity factors of 1.90, 1.67, and 1.96 were obtained for 1-H, 2-H, and 3-H, respectively. Separation can also be performed on the carbenium ions on regular Chiralpak IA CSP using water-containing eluents, thus allowing for enantiomeric purity determinations in aqueous environments. Resolution of neutral and cationic helicenes is also achieved on more recently developed LARIHC columns. The versatility of the cyclofructan phases allows for baseline separations for both cases and their loading capabilities are demonstrated. Finally, the configurational stability of 1+, 2+, and 3+ was measured. For each replacement of an oxygen atom by an amino group, the racemization barrier increases significantly (ΔG‡ = 29.8, 36.3 and >37 kcal mol(-1) for 1+, 2+, and 3+ respectively).

Gram Scale Conversion of R-BINAM to R-NOBIN.

A mild, operationally simple, and single-step transition-metal-free protocol for the synthesis of enantiomerically pure (R)-(+)-2'-amino-1,1'-binaphthalen-2-ol (R-NOBIN) from (R)-(+)-1,1'-binaphthyl-2,2'-diamine (R-BINAM) is reported. The one-pot conversion proceeds with good yield and shows no racemization. The hydroxyl on the R-NOBIN product was shown to have come from water in the reaction medium via an H2(18)O study. The correct value of the specific rotation of R-NOBIN was reported.

Enantiomeric separations of α-aryl ketones with cyclofructan chiral stationary phases via high performance liquid chromatography and supercritical fluid chromatography.

Normal phase chiral HPLC and SFC methods are presented for the enantiomeric separation of 21 α-aryl ketones with a unique class of chiral stationary phases (CSPs) based on cyclofructans (CFs). Separations were achieved for all but 2 analytes, with 17 compounds attaining baseline separation having resolution values up to 4.0. Most separations obtained in HPLC could be transferred to SFC, but the HPLC resolutions were generally better due to greater enantiomeric selectivity values. A structure-separation relationship (SSR) was developed to identify important structural features for separation of this class of compounds using CF-based CSPs. Preliminary studies are also presented that demonstrate the utility of the CF CSPs to investigate the base-induced enantiomerization of α-aryl ketones. It was demonstrated that even small amounts of base (0.01%v/v) in the mobile phase results in rapid, on-column, enantiomerization. Lastly, CSPs composed of superficially porous particles were used to achieve comparable separations of this class of chiral compounds, but at a fraction of the analysis time compared to CSPs composed of fully porous particles.

Screening primary racemic amines for enantioseparation by derivatized polysaccharide and cyclofructan columns.

It is a challenge to separate the enantiomers of native chiral amines prone to deleterious silanol interactions. A set of 39 underivatized chiral primary amines was screened for enantiomeric separation. Seven recently introduced commercial chiral columns were tested. They included six polysaccharide based chiral stationary phases (CSP) with bonded derivatives, ChiralPak® IA, IB, IC, ID, IE and IF columns and a cyclofructan derivatized CSP, Larihc® CF6-P column. Both the normal phase (NP) mode with heptane/alcohol mobile phases and the polar organic (PO) mode with acetonitrile/alcohol were evaluated. It was found that the cyclofructan based CSP demonstrated the highest success rate in separating primary amines in the PO mode with only one chiral amine not resolved. It is shown that, when screening the columns, there is no standard optimal condition; an excellent mobile phase composition for one column may be poorly suited to another one. Although butylamine was a good mobile phase additive for the polysaccharide columns in both PO and NP modes, it was detrimental to the enantio-recognition capability of the cyclofructan column. Triethylamine was the appropriate silanol screening agent for this latter column.

Screening primary racemic amines for enantioseparation by derivatized polysaccharide and cyclofructan columns☆ / 药物分析学报

It is a challenge to separate the enantiomers of native chiral amines prone to deleterious silanol interactions. A set of 39 underivatized chiral primary amines was screened for enantiomeric separation. Seven recently introduced commercial chiral columns were tested. They included six polysaccharide based chiral stationary phases (CSP) with bonded derivatives, ChiralPak? IA, IB, IC, ID, IE and IF columns and a cyclofructan derivatized CSP, Larihc? CF6-P column. Both the normal phase (NP) mode with heptane/alcohol mobile phases and the polar organic (PO) mode with acetonitrile/alcohol were evaluated. It was found that the cyclofructan based CSP demonstrated the highest success rate in separating primary amines in the PO mode with only one chiral amine not resolved. It is shown that, when screening the columns, there is no standard optimal condition;an excellent mobile phase composition for one column may be poorly suited to another one. Although butylamine was a good mobile phase additive for the polysaccharide columns in both PO and NP modes, it was detrimental to the enantio-recognition capability of the cyclofructan column. Triethylamine was the appropriate silanol screening agent for this latter column.

Enantiomeric separation of biaryl atropisomers using cyclofructan based chiral stationary phases.

Normal phase chiral HPLC methods are presented for the enantiomeric separation of 30 biaryl atropisomers including 18 new compounds recently produced via a novel synthetic approach. Three new cyclofructan based chiral stationary phases were evaluated. Separations were achieved for all but six analytes and the LARIHC™ CF6-P alone provided 15 baseline separations. Effects of polar modifiers and temperature effects also were studied. Apparent thermodynamic parameters were determined by van't Hoff plots. Preparative scale methods were developed and employed resulting in the first ever isolation of these novel atropisomers in their pure enantiomeric form. Insights into the mechanism of retention and chiral discrimination are presented.