Absolute Configuration and Enantiodifferentiation of a Hemicryptophane Incorporating an Azaphosphatrane Moiety

Abstract

The hemicryptophane racemate (±)-1 was optically resolved by semipreparative HPLC on Chiralpak IC column. The absolute configuration of each isolated enantiomer was established from the analysis of their electronic circular dichroism spectra. Enantiodifferentiation of the chiral cationic cage (±)-1 was evidenced in solution using Δ-TRISPHAT as chiral solvating agent, and the diastereomeric associations were observed in (1)H and (31)P NMR spectra.

Enantiopure encaged Verkade's superbases: Synthesis, chiroptical properties, and use as chiral derivatizing agent

“…H NMR (400 MHz, CDCl 3 ) δ 7.32 (s, 3H), 6.97 (s, 3H), 6.15 (d, J = 8.27 Hz, 6H), 6.01 (d, J = 8.27 Hz), 4.82-4.93 (m, 3H), 4.89 (d, J = 13.6 Hz, 3H), 4.45 (d, 1 J P-H = 491 Hz, 1H, P-H), 4.42-4.19 (m, 9H), 3.87-3.74 (m, 3H), 3.64 (d, J = 13.5 Hz, 3H), 3.57 (s, 9H), 3.36-3.47 (m, 3H), 3.31-3.17 (m, 9H), 2.68-2.76 (m, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ 158.27, 147.20, 146.45, 132.03, 131.71, 131.31, 129.01, 114.95, 114.61, 112.74, 70.23, 65.65, 55.12, 50.38, 47.63, 42.54, 36.80; 31 P NMR (121 MHz, CDCl 3 ) δ −31.98. These data are consistent with those reported in the literature 25. …”

“…Chromatography on these species required a solvent mixture in the mobile phase that degraded the stationary phase, leading to very low product recovery from the process. 25 In the present report, we chose to resolve the racemate of the key CTV intermediate 5 (Schemes 1 and S1), which can be effectively done on a large scale. In this manner, enriched (P)-3 and (M)-3 can be obtained at the hundred mg scale.…”

“…As CTV units can racemize before the ring closure of the cage (the energy barrier of racemization of CTV compound being around 112 kJ•mol −1 at 298 K), 24 the enantiomeric purity of these compounds was checked by adding chiral hexacoordinated phosphorus TRISPHAT anion (Tris (tetrachlorobenzenediolato)phosphate(V) anion, Figure 1). 25,[29][30][31][32][33][34][35][36][37][38] This anion presents a righthanded or left-handed propeller geometry of Δ or Λ configurations, respectively, and is a useful chiral solvating agent (CSA) for the NMR discrimination of enantiomers of chiral cationic and certain neutral organometallic species. In a typical experiment, 1.0 equivalent of…”

Emergence of Hemicryptophanes: From Synthesis to Applications for Recognition, Molecular Machines, and Supramolecular Catalysis

“…123,124 The azaphosphatrane-hemicryptophanes PH + @15a was optically resolved by chiral semipreparative HPLC, leading to the enantiopure compounds PH + @M-15a and PH + @P- 15a. 125 Likewise, hemicryptophane-superbases P@15b, P@ 15g, and P@15i and their corresponding protonated forms were also obtained using the same synthetic pathway. Makita et al also prepared the encaged azaphosphatrane PH + @22, 126 but depronation of the PH + failed even with an excess of t-BuOK or sodium hexamethyldisilazide (Scheme 29).…”

Different Strategies for Obtaining Enantiopure Hemicryptophanes

“…However, chiral HPLC was reported as an effective tool for the resolution of one derivative of 33 incorporating an azaphosphatrane moiety in its southern part: PH + @33 (Scheme 9, b). 31 Scheme 9 (a) Synthesis of hemicryptophane 33 starting from 32. (b) Preparation of the encaged azaphosphatrane PH + @33…”