Determination of the Absolute Configuration of Pentacoordinate Chiral Phosphorus Compounds in Solution by Using Vibrational Circular Dichroism Spectroscopy and Density Functional Theory

Abstract

Vibrational circular dichroism (VCD) spectroscopic measurements and density functional theory (DFT) calculations have been used to obtain the absolute structural information about four sets of diastereomers of pentacoordinate spirophosphoranes derived separately from l- (or d-) valine and l- (or d-) leucine for the first time. Each compound contains three stereogenic centers: one at the phosphorus center and two at the amino acid ligands. Extensive conformational searches for the compounds have been carried out and their vibrational absorption (VA) and VCD spectra have been simulated at the B3LYP/6-311++G** level. Although both VA and VCD spectra are highly sensitive to the structural variation of the apical axis, that is, the O-P-O or N-P-O arrangement, the rotamers generated by the aliphatic amino side chains show little effect on both. The dominant experimental VCD features in the 1100-1500 cm(-1) region were found to be controlled by the chirality at the phosphorus center, whereas those at the C=O stretching region are determined by the chirality of the amino acid ligands. The good agreement between the experimental VA and VCD spectra in CDCl(3) solution and the simulated ones allows us to assign the absolute configurations of these pentacoordinate phosphorus compounds with high confidence. This study shows that the VCD spectroscopy complemented with DFT calculations is a powerful and reliable method for determining the absolute configurations and dominating conformers of synthetic phosphorus coordination complexes in solution.

Determination of Absolute Configuration of Chiral Molecules Using Vibrational Optical Activity: A Review

“…Over the past several years there has been a rapid growth in the use of VCD to determine the AC of small chiral organic molecules. A large variety of structural types have been examined, including epoxides and cyclopropanes, [55][56][57][58] bicyclic and tricyclic structures, [59][60][61][62][63][64][65][66][67] chiral structures with no chiral center (atropisomer or molecules with axial or helical chirality), [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83] sulfur or phosphorus containing compounds, 77,[84][85][86][87][88] flexible molecules, 56,[89][90][91] and other structures that do not fit into any of the above categories. [92][93][94][95][96][97] The following examples highlight the versatility of VCD as a powerful tool for the AC determinations of different types of chiral organ...…”

Chiral Hypervalent, Pentacoordinated Phosphoranes

“…More recently this approach based on the reaction of phosphorus trichloride with amino acids was used by Zhao and coworkers for the preparation of spirophosphoranes from enantiomerically pure valine 136a, isoleucine 136b and phenylalanine 136c. [111][112][113][114]. The spirophosphoranes formed as mixtures of diastereoisomers were separated to the pure stereoisomers 137a-c and 138a-c by reverse-phase HPLC or recrystallization (Scheme 56).…”

Diastereomers of the pentacoordinate chiral phosphorus compounds in solution: absolute configurations and predominant conformations

“…Previous studies showed that the slightly distorted TBP geometry is favoured, 15 and the O-P-O conformation is significantly more stable than the other three conformations. 12 For example, the related pentacoordinate spirophosphoranes derived separately from L (or D)-valine andleucine take on TBP O-P-O geometries at the potential minima while a transition state identified has the SP type geometry. 12 Because the large energy gap between the O-P-O apical axis conformers and the other three types of conformers and the similarity in the current samples and those in Ref.…”

“…11 In this article, we report the assignment of the absolute configurations and dominant conformations of four sets of diastereomers of chiral pentacoordinate spirophosphoranes (Chart 1) by using VCD spectroscopy, in conjunction with DFT calculations. Since only one structural determination by VCD spectroscopy was previously reported for pentacoordinate phosphorus compounds, 12 we have also investigated experimentally and theoretically the influence of solvents and the effects of basis sets and different functionals on the VA and VCD spectra for this type of coordination compounds.…”