Synthesis of new phosphino-oxazoline ligands for asymmetric catalysis

摘要

Borabox ligands proved to be efficient ligands for controlling the enantioselectivity of various udmetal-catalyzed reactions. Therefore modification of an existing borabox backbone was udimplemented and new borabox ligands modified on C(5) position of the oxazoline ring were udprepared and tested in the copper-catalyzed asymmetric cyclopropanation. In this study high udstereocontrol of the reaction was observed. However the presence of sterically demanding udgroups at position C(5) did not improve the results compared to the C(5) non-substituted udanalogs.udThe synthesis of analogous boron-bridged phosphino-oxazolines was attempted via several udsynthetic approaches in order to prepare new zwitterionic N,P-ligands. The simple stepwise udsubstitution by subsequent addition of lithiated oxazoline and phosphine was not possible. It udeither led to borabox ligands or to undesired dimeric species, which were inert towards udreaction with other nucleophiles.udWe decided to tune the electronic properties of the boron compound by variation of the udsubstituents in order to avoid multiple substitution or undesired dimer formation. Therefore udaminochloroborates were examined due to their lower reactivity compared to chloroboranes udor chloroborates. A derivative with a phosphine-aminoborate backbone was prepared but udunfortunately the decreased reactivity of the nitrogen-substituted boron center did not allow udanother nucleophilic addition of the oxazoline moiety. In order to avoid dimer formation the udreactivity of potassium diaryldifluoroborates was investigated. These tetrasubstituted boron udcompounds reacted with lithium oxazolines and provided products of nucleophilic udsubstitution at the boron center. The resulting oxazoline-substituted fluoroborates could be udisolated as zwitterions after protonation of the oxazoline nitrogen atom. However, the second udintended substitution with the phosphine moiety was not possible. In addition, quantum udchemistry calculations were carried out to support the experimental studies.udThe synthesis of new NeoPHOX ligands derived from inexpensive chiral aminoacids L-serine udand L-threonine was developed. These chiral ligands were tested in the iridium-catalyzed udasymmetric hydrogenation and palladium-catalyzed allylic substitution. In both reactions the udenantioselectivities achieved were excellent for most of the substrates tested. In the iridium udcatalyzed hydrogenation it was found that presence of an acid-stable protecting group of udtertiary alcohol (R2) is necessary in order to achieve full conversions. The enantioselectivities udobtained in the catalytic asymmetric hydrogenation and allylic substitution with the L-serine udand L-threonine derived ligands were almost identical to those reported for tert-butyl-udsubstituted NeoPHOX ligands, which are derived from very expensive amino acid tert-udleucine.udThe use of Ir catalysts for the diastereoselective hydrogenation of Diels-Alder products was udinvestigated. The best results were obtained with a pyridine-phosphinite complex that udafforded the saturated cyclohexane derivatives with diastereoselectivities of up to 98:2 and udfull conversion. The reaction is strongly catalyst-controlled, so it is possible to obtain each of udthe two diastereomeric products with high selectivity using either (R)- or (S)-catalyst.ud