Atropisomerism at the carbon–phosphorus bond

Abstract

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  Discovery and isolation of C–P atropisomers
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  High configurational stability and threefold stereogenicity
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  Regio-, diastereo-, and enantiocontrol of C–P atropisomers by catalytic C–H activation
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  Application of C–P atropisomers for absolute configuration determination

Chiral organophosphorus compounds with defined relative and absolute configuration have evolved into a mainstay in synthesis and catalysis. However, besides systems with a chiral backbone, P-stereocenters remained the only configurationally stable stereogenic unit based on phosphorus. The properties of the stereoisomers with P-stereocenters, their stereoselective synthesis, and their diverse applications were investigated in detail. Nevertheless, despite the numerous functionalities based on the C–P bond, isomers resulting from the restricted rotation about the C–P bond have not yet been described. In contrast, the immense range of atropisomers with high rotational barriers about the C–C or C–N bonds advanced to a cornerstone of stereochemistry. Owing to their longer bond lengths and higher flexibility, only C–S and C–I bonds have been established as configurationally stable stereogenic axes with elements beyond the second row. Given their significance in organic chemistry, we evaluated the viability to halt the rotation about the C–P bond. We discovered that triptycyl phosphine oxides with threefold stereogenic C–P axes feature rotational barriers sufficiently high to separate C–P atropisomers under ambient conditions. Furthermore, a regio- and diastereoselective synthesis was developed to catalytically control the configuration of C–P atropisomers via a Fujiwara-Moritani reaction, and the feasibility of enantiocontrol was confirmed. Given the diversity of organophosphorus chemistry, it is expected that the atropisomerism at the C–P bond and the stereoselective synthesis of configurationally stable C–P atropisomers will enable the preparation of structurally well-defined molecular architectures to advance reaction development, ligand design, catalysis, and the assembly of functional systems.

The feasibility of halting the rotation about a C–P bond is reported. At the outset, atropisomers with configurationally stable stereogenic C–P axes were synthesized in the form of triptycyl phosphine oxides with threefold stereogenicity. Their bond rotational profile revealed that each of the three barriers amounts to more than 115 kJ/mol, which permits the isolation of the antiperiplanar and the two enantiomeric synclinal C–P atropisomers under ambient conditions. Furthermore, the feasibility of their atroposelective synthesis by desymmetrization was established to catalytically control the configuration of stereogenic C–P axes. A first application of the synthesized C–P atropisomers was demonstrated by determining the absolute configuration of a protected amino acid.

The feasibility of halting the rotation about a C–P bond is reported. At the outset, atropisomers with configurationally stable stereogenic C–P axes were synthesized in the form of triptycyl phosphine oxides with threefold stereogenicity. Their bond rotational profile revealed that each of the three barriers amounts to more than 115 kJ/mol, which permits the isolation of the antiperiplanar and the two enantiomeric synclinal C–P atropisomers under ambient conditions. Furthermore, the feasibility of their atroposelective synthesis by desymmetrization was established to catalytically control the configuration of stereogenic C–P axes. A first application of the synthesized C–P atropisomers was demonstrated by determining the absolute configuration of a protected amino acid.

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