Pirkle’s reagent

Pirkle s reagent, a chiral solvating agent, was used to determine the absolute configuration of the annonaceous butenolides by the NMR method <02CEJ5662>. 

Fig. 34a, b. H-NMR spectrum of 86 a) after addition of an excess of KPF6 b) in the presence of Pirkle s reagent (signals indicated by black squares). Note that important splitting can be observed for the signals of Hm and H, (black arrows)... 

In a chiral medium, enantiotopic protons become diastereotopic and thus their 1H-NMR signals are split (see ref. [87]). Therefore, a positive test with the Pirkle s reagent is the necessary but not sufficient condition for chirality... 

A different principle was employed to obtain inherently chiral calix[4]arenes. This approach involves desymmetrizing C2v or Cs symmetrical calix[4]arenes or calix[4]arene analogues (see Section 4.5) by etherification. 1,3-Diethers 78a of AABB-type calix[4]arenes are (as usually) easily obtained in a stereochemically fixed syn-arrangement.146 Since the symmetry plane of the calix[4]arene skeleton does not coincide with the two symmetry planes of the diether-pattem, the whole molecule is C, symmetrical, as revealed by the NMR spectrum. The chirality has been additionally demonstrated by further splitting of the signals in the presence of Pirkle s reagent.147 For the same reasons 1,2-diether derivatives 78b of ABAB-type calix[4]arenes are chiral, although less easily accessible.148... 

Bis- -diketones have been demonstrated to be powerful ligands in the engineering of supramolecular architectures. Pikramenou and coworkers [53a] used two bis-P-diketones of l,3-bis(3-phenyl-3-oxopropanoyl)benzene (H2L ) and l,3-bis(3-phenyl-3-oxopropanoyl) 5-ethoxy-benzene (H2L ) to synthesize neutral homodimetallic complexes [Ln2(L )3] (Ln = Eu, Nd, Sm, Y, Gd) and [Ln2(L )3] (Ln = Eu, Nd) and also an anionic dinuclear lanthanide complex [Eu2(L )4] . The detailed studies by NMR, electrospray, and MALDI (matrix assisted laser desorption ionization) mass spectrometry, by addition of chiral Pirkle s reagent, revealed that [Ln2(L" )3] and [Eu2(L )4] (see Eigure 2.38) are chiral, and have triple- and quadruple-stranded supramolecular structures, respectively, with the latter being more strongly emissive than the former. 

This bis-copper complex 252+.(BF4 )2 is a dark red crystalline solid (needles). The high resolution mass spectrum (FAB) of 252+.(BF4 )2 shows a molecular peak at 1816,74 (calculated molecular weight for 25 + = 1817.10). The NMR spectrum of 25 + is in complete agreement with its structure. Since 25 + contains a double helix on two copper(I) atoms, it is chiral. This was demonstrated in the presence of Pirkle s reagent.[33] In order to prove the knotted topology of 25 +, we had to consider the various possible compounds obtained in the cyclisation reaction. From a tetrafunctional double helicoidal precursor, several 2+2 connections are possible, with the most probable ones being indicated in Figure 11. 

The structure found in the crystalline state (Figure 2) is also maintained in solution, as shown by H-NMR spectroscopy in the presence of Pirkle s reagent. The four doublets (meta-coupling) observed for the aromatic protons in the corresponding amide 20b obtained with diaza-18-crown-6 must be explained in a similar way. 

Apart from NMR spectral patterns showing moleculeu asymmetry, evidence of chireility for cone 10 and partial cone structures 11 and 13 was provided by the addition of Pirkle s reagent (S)-(-H)-(9-anthryl)-2,2,2-trifluoroethanol to a chloroform solution of each calixarene, which caused doubling of (in principle) all signals. 

FIGURE 13 H NMR spectrum (300 MHz) of ( ) c/s-d-lactone in presence of (-)-2,2,2-trifluoro-1-(9-anthryl)ethanol (Pirkle s reagent). 

In the case of the direct method , NMR spectra of enantiomers are recorded in the presence of a nonracemic chiral solvating agent (CSA, Pirkle s method)78, or after addition of a paramagnetic chiral (nonracemic) lanthanide shift reagent (LSK) to the solution of the sample. 

Another useful reagent for alcohols is Pirkle s (-)-(/ )-l-(l-naphthalenyl)ethyl isocyanate (14)161. For example, it was used to separate the two diastereomeric carbamates obtained from rue-13. The carbamate shown by X-ray analysis to have structure 15 was cleaved162 to furnish (+ )-strigol (13), the witchweed germination factor, thus confirming the absolute configuration of 13163. 

The reagent itself may be chiral. Enantiopure forms of l,l -bi-2-naphthol are readily available [35] and can be complexed with lithium aluminum hydride (LAH) to form the selective reducing agent BINAL-H, which reduces a variety of ketones, including the precursor to Pirkle s alcohol, 3.13, a chiral solvating agent mentioned in Section 3.3 (Eq. 3.7) [36]. 

The separation of enantiomers can be effected either by transforming them into diastereoisomers using a chiral reagent and separating them on conventional phases or by separating the enantiomers on chiral phases. The utilization of chiral phases has not yet become routine, but studies of enantiomeric dipeptides have been carried out (115,116). Pirkle et al. (117) and Hyun et al. (118) separated enantiomeric di- and tripeptides (methyl esters of /V-3-5-dinitrobenzoyl derivatives) on chiral stationary phases (CSPs) derived from (R)-a-arylalkylamines, (S)-N-(2-naphthyl) valine, or (S)-1 -(6,7-dimethyl-1 -naphthyl) isobutylamine. These workers were able to separate four peaks for each dipeptide derivative, corresponding to the two enantiomeric pairs (R,R)/(S,S) and (R,S)/(S,R). Cyclodextrin-bonded stationary phases and chiral stationary immobilized a-chymotrypsin phases were used to separate enantiomeric peptides (118a,b). 

Kainosho M, Ajisaka K, Pirkle W H, Beare S D 1972 The use of chiral solvents or lanthanide shift reagents to distinguish meso from d or 1 diastereomers. J Am Chem Soc 94 5924-5926... 

---