A commercially available 2,3-unsaturated pyranoside, derived from d-glucose, was converted into a new type of olefin phosphorus chelate ligand in only three steps. Application in rhodium catalyzed conjugate additions of phenylboronic acid to enones led to excellent levels of stereoinduction for several cyclic substrates. The easy preparation and the high efficiency of this ligand make it an interesting and promising alternative to established systems.
A new type of carbohydrate-based bis(oxazoline) ligands was prepared from inexpensive D-glucosamine and tested in asymmetric cyclopropanation reactions. For optimisation, modified ligands with 3-O substituents of varying size and electronic properties were prepared as well as a 3-OH unprotected and a perpivaloylated derivative. All new ligands were tested in asymmetric cyclopropanation, revealing a strong dependence of enantioselectivity on steric demand
Highly efficient pseudo-enantiomeric olefin ligands were designed from D-glucose and D-galactose. These ligands yield consistently excellent levels of enantioselectivity in Rh(I)-catalyzed 1,4-additions of aryl- and alkenylboronic acids to achiral enones and high diastereoselectivity with chiral substrates. Contrary to established olefin ligands, they are obtained enantiomerically pure via short syntheses without racemic resolution steps, making them a valuable addition to the arsenal of chiral ligands with olefinic donor sites.
SummaryIn previous studies we found that the asymmetric induction of bis(oxazolines) based on D-glucosamine strongly depended on the steric demand of the 3-O-substituents. To further probe the impact of the 3-position of the pyranose scaffold, we prepared 3-epimerised and 3-defunctionalised versions of these ligands as well as a 3-O-formyl derivative. Application of these new ligands in asymmetric cyclopropanation revealed strong steric and configurational effects of position 3 on asymmetric induction, further dramatic effects of the pyranose conformation were also observed.
An efficient route to derivatives of carbohydrate-based bis(oxazoline) ligands with 3-O substituents of varying steric demand is described. The synthesis of the new ligands proceeds via a thioglucoside key intermediate, the double cyclisation reaction to the desired bis(oxazolines) is initiated with N-iodo succinimide under mild conditions. Employing this strategy, four new 3-O-modified bis(oxazoline) ligands were obtained in good yields.Asymmetric metal-catalysed transformations are one of the most efficient methods for preparation of chiral compounds. To achieve high levels of asymmetric induction, optimisation of the chiral ligands employed is often necessary. Therefore the design of new ligand structures is a very active field of research today.Carbohydrates, although far less frequently employed than other compounds from the chiral pool, are versatile starting materials for the preparation of novel and unusual chiral complex ligands. 1 In the course of our work we became interested in chiral bis(oxazoline) ligands, which are successfully applied in many asymmetric reactions. 2 Recently we introduced two new carbohydrate-based ligands, glucoBox and glucoPybox, which were prepared via bis(amides) of D-glucosamine using a one-pot double cyclisation reaction. 3,4 The glucoBox ligand was employed in cyclopropanations affording enantioselectivities up to 82% ee, 3 while the glucoPybox ligand yielded up to 99% ee in the alkynylation of imines. 4 To further increase the enantioselectivity for the cyclopropanation with the carbohydrate box and to extend the substrate scope for the carbohydrate pybox ligand, we decided to perform systematic modifications on the ligand scaffold to obtain optimised ligands through structural variation.The backbone of the new carbohydrate ligands offers many options for structural modifications, as a wide range of residues with varying steric and electronic properties can be attached to the hydroxy groups of the pyranose subunits. Especially the 3-O substituents located next to the oxazoline nitrogen atoms can be expected to have considerable impact on steric shielding coordinated of metal centres (Figure 1). This in turn will directly influence the stereoselectivity of reactions involving substrates bound to the metal centres. We therefore set out to prepare a series of ligands with 3-O substituents of varying steric demand, choosing 3-O-Me as a small, 3-O-Bn as a mediumsized and 3-O-TES as a large residue (Figure 1). To selectively access the 3-O position, we planned to employ benzylidene acetals to block the 4-and 6-hydroxyls. Our studies towards these target structures were done on the glucoBox scaffold. Figure 1 General structure of carbohydrate bis(oxazoline) ligands and points for the attachment of substituents with varying steric demand
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