Phospholanes synthesis

Hoge G (2004) Stereoselective cyclization and pyramidal inversion strategies for P-chirogenic phospholane synthesis. J Am Chem Soc 126 9920-9921... 

Burke MJ, Feaster JE, Harlow RL (1991) New chiral phospholanes synthesis, characterization, and use in asymmetric hydrogenation reactions. Tetrahedron Asymm 2 569-592... 

The conventional synthesis of trans-2,5-dialkyl phospholanes starting from a chiral 1,4-diol is shown in Scheme 24.1. Originally, these 1,4-diols were obtained via electrochemical Kolbe coupling of single enantiomer a-hydroxy adds [25], but this method proved to be commercially impracticable and has since been replaced by more viable biocatalytic routes [26]. Reaction of the chiral 1,4-diol with thionyl chloride followed by ruthenium-catalyzed oxidation with so-... 

Enantiomerically pure amines are extremely important building blocks for biologically active molecules, and whilst numerous methods are available for their preparation, the catalytic enantioselective hydrogenation of a C=N bond potentially offers a cheap and industrially viable process. The multi-ton synthesis of (S)-metolachlor fully demonstrates this [108]. Although phospholane-based ligands have not proven to be the ligands of choice for this substrate class, several examples of their effective use have been reported. 

Indeed, the imine intermediate 142 in the synthesis of metolachlor has been reduced in 97% ee using an iridium complex of the phospholane-containing ligand 55 [80]. 

The ligand synthesis is straightforward, using amino alcohols as the source of chirality in the oxazoline ring, whereas the stereochemistry in the phospholane ring is controlled by an enantioselective deprotonation using sparteine (Scheme 29.2). 

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