Rhodium-Catalyzed Asymmetric Hydroformylation with Taddol-Based IndolPhos Ligands

A small library of Taddol-based IndolPhos ligands 2a-g and their use in asymmetric hydroformylation (All F) reactions are reported. Moderate to good enantioselectivities are obtained for styrene, vinyl acetate, and allyl cyanide up to 72%, 74% and 63% ee, respectively. High b/l ratios are obtained, which results in a high net yield of the desired chiral aldehyde. An unprecedented temperature-dependent reversal of enantioselectivity is found when using ligands 2d,e, which are based on a xylyl-derived Taddol in the Rh-catalyzed All of styrene. Furthermore, these ligands give the opposite enantiomer of the product for vinyl acetate and allyl cyanide when compared to the other library members, all of which are based on (R,R)-tartaric acid. Ligands 2a and 2d display a similar kinetic profile, which is best described by type I kinetics. Deuterioformylation experiments have shown that insertion of the alkene into the Rh H bond is irreversible under the conditions applied. High-pressure NMR studies indicate that the hydridobiscarbonyl rhodium species, which is the resting state of the catalyst, features equatorial apical coordination of the ligands with a preference for the phosphine on the apical position, isomer A. However, in the case of ligand 2d the isomer in which the phosphoramidite occupies the apical position. B, is only marginally higher in free energy than isomer A. It is proposed that formation of the product takes place via isomer B for ligands 2d,e and via isomer A for all other ligands, explaining the observed reversal of enantioselectivity.