Tetrahedron, asymmetry最新文献

In routine small-molecule single crystal structure determination, accurate absolute structure determination has sometimes been challenging. Developments in diffractometers, X-ray sources, detectors and software, along with new concepts for the elucidation of the absolute structure have seen the greatest advances in recent times. Nonetheless, determining the absolute structure of a crystal, particularly when only light atoms are present, requires some thought in the planning of the experiment in order to obtain the best possible data and some care in modelling the structure and interpreting the results so as not to draw incorrect or unsupported conclusions. Some practical recommendations for best practice and how to avoid pitfalls and misinterpretations are presented as a guide, particularly for those new to the field of crystal structure analysis.

General strategies by which NMR spectroscopy can be used to assign absolute configuration are discussed. These include the use of chiral derivatizing and chiral solvating agents. Areas that are well developed and areas of need in this field are described. The future potential of using aligning media such as chiral liquid crystals and odd-parity effects that may make it possible to determine absolute configuration without the need for an enantiomerically pure reagent are discussed.

Howard Flack made significant contributions to many branches of crystallography (J. Appl. Cryst. 2017, 50, 666–667), but he was probably best known for his derivation of an expression for the robust determination of the absolute structure of crystals, and hence of the absolute configuration of the molecules from which they were made (Acta Cryst. 1983, A39, 876–881). This expression included a parameter which Flack called ‘x’, but which the rest of the world called ‘The Flack Parameter’.

Students of single crystal X-ray diffraction are often give advice as to how best to collect their data when attempting absolute configuration determination. These ‘rules’ often have more grounding in gut-feeling than evidence. Thus, in an effort to provide advice and evidence that today’s crystallographers can pass onto to tomorrow’s young scientists, we present a systematic study of 1-deoxy-l-arabinitol, a straight chain sugar which crystalises well in the space group $\text{I}{4}_1$.

The utility of enantiopure BINOL (1,10-Bi-2-naphthol), in a ternary ion-pair complex, which is obtained using a carboxylic acid and an organic base, as a versatile chiral solvating agent (CSA) has been demonstrated for chiral analysis and the absolute configuration assignment of hydroxy acids. Another protocol where the utility of NOBIN as a CSA has been developed for discrimination and absolute configuration assignment of acids, hydroxy acids and their derivatives with a distinct strategy where a third ingredient, p-toluenesulfonic acid (p-TsOH) serves as a linker. In addition some three component chiral derivatization protocols have been introduced, such as the use of 2-formylphenylboronic acid and enantiopure mandelic acid or a primary amine for the determination of the configuration of primary amines and hydroxy acids, respectively. A simple, rapid and highly efficient three component chiral derivatizing protocol has also been discussed which was developed for assigning the absolute configuration of chiral α-hydroxy acids and their derivatives, which involves the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and (S)-[1,1-binaphthalene]-2,2-diamine separately. In a few examples, the DFT based theoretical calculations have been carried out to determine the geometry optimized structures of the complexes.

The present study investigates a synthetically simple ferrocene derivatization of natural products and active pharmaceutical ingredients. Seven new crystal structures are analyzed together with 16 structures of ferrocene derivatives reported previously. In all cases, the unambiguous determination of the absolute structure was established from anomalous dispersion using the methods of Flack and Parsons. A comparison with other derivatization approaches shows the advantage of the described ferrocene derivatization for establishing the absolute configuration of novel compounds.

The asymmetric 1,3-dipolar cycloaddition of an imino ester 5 with tert-butyl acrylate is catalyzed by a dual chiral silver(I) complex formed from a chiral phosphoramidite 14 and the chiral silver(I) binolphosphate (R)-17. This reaction is selected to achieve the synthesis of enantiomerically enriched key structures to access the third generation of GSK HCV inhibitors. The scope of this dual chiral catalytic system is analyzed by employing different imino esters and dipolarophiles, and also compared with the same cycloaddition reactions performed with the chiral phosphoramidite 14·AgClO₄ complex.

The synthesis of acetyldioxanes 4 and 9a starting from (−)-(1R)-myrtenal is described. The products were treated with a representative series of nucleophilic reagents (RMgX, RLi, NaBH₄ and LiAlH₄) to assess the effect of the substituent at C-3 on the stereochemical outcome. It was observed that the nucleophiles preferred the re-face of the CO group when the equatorial substituent at C-3 was a methyl group, whereas a phenyl group at the same position induced the addition through the si-face, thus allowing access to either desired stereochemistry of a final product. This behavior suggests that the formation of the expected Cram-chelated coordination complex takes a coplanar orientation with the C-3 equatorial substituent. Moreover, Grignard reagents were the most stereoselective nucleophiles. The stereochemistry of the addition was established by X-ray diffraction and chemical correlation.