Synthesis and Applications of P-chirogenic Phosphine Boranes
Doctoral thesis, 2006
This thesis reports the independent synthesis of both enantiomers of P-chirogenic phosphine ligands and the building blocks thereof, which are suitable for parallel synthesis efforts and for the generation of more diverse libraries of P-chirogenic compound. The use of P-chirogenic phosphine boranes in transition metal-catalyzed reactions, such as palladium-catalyzed allylic alkylation and amination, is also described.
Papers I and II describe the synthesis and evaluation of different chiral diamines in the enantioselective deprotonation of alkyl- and aryl-substituted prochiral phosphine boranes. Although (-)-sparteine ligated to sec-BuLi is reported to give high enantioselectivity in the deprotonation of prochiral phosphine-borane, this methodology suffers from the lack of availability of (+)-sparteine. We have shown that diamines derived from the quinolizidine alkaloid (-)-cytisine, which is extracted from the Golden Rain Tree (Laburnum anagyroides), are excellent substitutes for (+)-sparteine and thus facilitate the preparation of both enantiomers of a P-chirogenic phosphine via enantioselective deprotonation.
The utility of P-chirogenic scaffolds obtained by desymmetrization is presented in Papers III, IV and V. A set of new P-chirogenic building blocks was synthesized via asymmetric deprotonation and utilized in the further syntheses of libraries of different P,N ligands or α-carboxyphosphine boranes. Applications of the phosphine boranes as pro-ligands in palladium-catalyzed reactions are also described.
In Paper VI, a novel biocatalytic desymmetrization of prochiral phosphine-boranes mediated by lipase B of Candida antarctica is presented. Both enantiomers can be prepared with good to excellent enantioselectivity either through hydrolysis of a prochiral diacetate or via acylation of a prochiral diol.
Finally, Paper VII describes a highly stereoselective and enantioselective Au(I)-catalyzed intermolecular olefin cyclopropanation. This reaction is based on an intermediate gold-carbenoid species, derived via a Rautenstrauch rearrangement of different propargyl esters, which is trapped by olefin to form multi-substituted cyclopropanes with defined regiochemistry and stereochemistry.
In summary, this work has extended the area of P-chirogenic phosphine ligands to include both enantiomers at phosphorus, via either enantioselective deprotonation or enzyme catalysis. The importance of P-chirogenic phosphine ligands in asymmetric catalysis is displayed by their frequent as ligands to transition metals in the synthesis of all kinds of chiral compounds, including several different pharmaceuticals. Accordingly, access to both enantiomers of a chiral ligand is of outmost importance. These ligands, as well as and ligands having axial chirality, have then been utilized successfully in palladium catalyzed allylic alkylation and in gold catalyzed olefin cyclopropanation, affording chiral material of high optical purity.
gold(I) catalysis lipase
enantioselective cyclopropanation. enantioselective deprotonation