Synthesis, Conformational Studies, X-ray Structures, and Complexation Properties of Semirigid Macrocyclic Phosphonamides

Abstract

The semirigid phosphonamide ligands 1-5 have been synthesized from the macrocyclic precursors 6-9 by reaction with 1,3-propanediol ditosylate or 1,2-dichloroethane. For the thiophosphoryl compounds 1 and 2, and the phosphoryl derivative 5, the reactions were carried out in biphasic aqueous NaOH solutions. The phosphoryl derivatives 3 and 4 were better obtained from NaH in anhydrous tetrahydrofuran. The conformations of the hosts in solution were deduced from low-temperature NMR and NOE difference experiments. Conformational equilibria between exo and endo forms are observed for the 18-membered macrocycles 1 and 3. The exo conformer predominates in solution for the 21-membered macrocycle 2, whereas 4 exists as rapidly exchanging conformers. The X-ray crystal structures of macrocycles 1, 2, and 5 have been determined as well as the complexes 1.Hg(SCN)(2) and 5.LiNO(3). In the Hg(2+) complex the metal ion is located out of the macrocyclic cavity and is coordinated to the thiophosphoryl unit. In 5.LiNO(3)()()the Li(+) cation is located inside the macrocyclic cavity and is coordinated to a tetrahedral array of oxygen donors. Free energies of complexation (DeltaG degrees ) of the phosphorylated ligands 3-5 with alkali metal and ammonium cations were determined in CHCl(3) saturated with H(2)O by picrate extraction experiments. The -DeltaG degrees values are greatest for 4 complexing K(+) and NH(4)(+) (7.3 and 8.0 kcal/mol, respectively). The relationships between structure and binding are discussed.

Synthesis, Molecular Structure, and Binding Properties of a Hemispherand Incorporating a Phosphoryl Hard Donor Group

“…For the rigidification step, the use of the biphasic technique described by Cram, [10] which had proved to be efficient with nonmethoxylated derivatives, [8] failed in the case of the thiophosphorylated and phosphorylated derivatives 1 and 2. Therefore, we performed the rigidification step under anhydrous conditions.…”

“…The assignment of the stereochemistry of the conformers was based upon comparison of the NMR data of 3 with those of the corresponding unsubstituted derivatives 5. [8] The similarity of the NMR data allows the assignment of the highfield signal to the endo conformer and the downfield signal to the exo one. The proton-decoupled 31 P NMR spectrum of 3 (CD 2 Cl 2 , 80 MHz) is given as a function of temperature in Figure 1, and emphasizes the dynamic nature of the conformational equilibrium.…”

“…[5] Recently, we reported that phosphorus macrocycles could be obtained by the reaction of a diamine with a diaminophosphane and subsequent oxidation of the P III species. [6,7] We have extended this chemistry to rigidified phosphorus molecules, [8,9] and this paper deals with the synthesis and the properties of the first phosphorylated hemispherand 3 and its macrocyclic precursor 2. The binding activities of 2 and 3 towards alkali metal and ammonium cations were examined to assess the role of the phosphoryl group and of the conformational flexibility in recognition.…”

“…Crystal structure of 3´(CH 3 ) 2 CO´CH 3 OH. [16] Selected bond lengths [] and angles [8]: P 28 ± N 1 1.677 (3), P 28 ± C 31 1.777 (6), P 28 ± O 32 1.489 (4), C 28-N 1-P 28 115.9 (2), C 5-N 1-P 28 113.5 (2), C 5-N 1-C 28 114.9 (2), N 1-P 28-O 32 114.93 (13), N 1-P 28-C 31 106.1 (2), N 1-P 28-N 1* 101.2 (2), C 31-P 28-O 32 112.5 (2).…”

“…Atoms O 8 and O 17 are not coordinated, reflecting the small size of the cation compared to the available macrocyclic cavity. [16] Selected bond lengths [] and angles [8]: P 28 ± N 24 1.665 (3), P 28 ± N 1 1.670 (3), P 28 ± C 35 1.792 (4), P 28 ± O 36 1.465 (3), Na ± O 11 2.488 (4), Na ± O 14 2.454 (4), Na ± O 33 2.634 (3), Na ± O 36 2.249 (3), Na ± O 37 2.546 (3), Na ± O 39 2.363 (4), C 1-N 24-P 28 119.0 (2), C 3-N 24-P 28 116.9 (2), C 1-N 24-C 3 116.9 (3), C 5-N 1-P 28 117.7 (2), C 7-N 1-P 28 115.6 (2), C 5-N 1-C 7 115. 5 (3), N 24-P 28-O 36 114.0 (2), N 1-P 28-O 36 114.3 (2), N 24-P 28-C 35 109.0 (2), N 1-P 28-C 35 108.1 (2), N 24-P 28-N 1 100.1 (2), C 35-P 28-O 36 110.7 (2).…”