Design,Synthesis And Application Of Catalysts For Cyanohydrin Hydration And Asymmetric Dihydroxylation Of Olefin

Catalytic nitriles hydration that generates widely used amides is one of the most important issues in both laboratory and industrial synthetic chemistry.Hydration of cyanohydrins（α-hydroxyl nitriles）that are readily available through cyanation of aldehydes and ketones provides the most straightforward route to valuableα-hydroxyamides.However,due to the low stability of cyanohydrins and deactivation of the catalysts by the released HCN,catalytic direct hydration of cyanohydrins is remians underdeveloped.Non-covlent interations（NCIs）involving aromaticπsystems have mainly studied in stabilizing the structure of biological molecules and small molecule catalysis.The classic Sharpless asymmetric dihydroxylation（SAD）reaction is widely applied to convert prochiral alkene substrates into chiral vicinal diols with excellent stereoselectivities of olefin substrates.In contrast to its widespread applications in the synthesis of chiral vicinal diols,the use of SAD reaction for the kinetic resolution of racemic olefins has remained unsolved.This thesis realizes the Pt-catalyzed nitrile hydration mechanism,highly efficient Pt-catalyzed cyanohydrins hydration and Non-covalentπinteractions directed kinetic resolution based on asymmetric dihydroxylation.Mainly as follows:Firstly,the mechanism of Pt-catalyed nitrile hydration has been throughly explored by ³¹P NMR monitoring,X-ray crystallography and ¹⁸O-labeling experiments.The important five-membered metallacyclic ring intermediate has been confirmed by ³¹P NMR X-ray,proving the hypothesis of intramolecular nucleophilic attack of the hydroxyl group of phosphine oxide ligand on the coordinated nitrile by Parkins in 1995X ray crystallography and ¹⁸O-Labeling experiments confirmed the catalytic cycle that involves a five-membered metallacyclic intermediate and subsequent hydrolysis via attacking of the phosphorus of the PMe₂OH ligand by H₂O.Secondly,based on the above investigation of the nitrile hydration mechanism,high efficient cationic Pt-catalysts for challenging cyanohydrin hydration has been developed.Pt-catalysts containing an electron-rich bis-phosphine ligand with a small bite angle and electron-deficient phosphine oxide ligand were designed and synthesized.These novel Pt-catalysts were successfully used in hydration of cyanohydrins and sterically hindered nitriles.They display noticeably enhanced catalytic activity toward aldehyde-derived cyanohydrins with excellent TONs up to 2600 under mild conditions.For the exteremely unstable cyanohydrins derived from ketone compounds,the catalytic activity of the Pt-catalysts reach TON up 383 withα,α-dialkyl-substituted cyanohydrins,132 withα,α-diaryl-substituted cyanohydrins,and 4000 with sterically hindered nitriles.Lastly,asymmetric dihydroxylation based kinetic resolution of allylic amids has been expored by rationally incorporating lone pair-πinteraction between substrate and catalyst.Sharpless asymmetric dihydroxylation has been widely utilized to convert inert alkenes into useful chiral diol products,however,kinetic resolution of racemic alkene substrates via this strategy remains difficult.The key for successful a kinetic resolution was that the racemic chiral center of the substrate needs to be included in the catalyst-substrate interaction framework.Therefore,our strategy was to introduce an electron-deficientπ-acceptor on C9 chirality of the cinchona alkaloid ligands and at the same time using carbonyl lone pair of the amide functionality of allylic amide substrates to establish a lone pair-πinteraction between substrate and ligand.The electron-deficient triazine ring was screened as the optimalπ-acceptor.Therefore,asymmetric dihydroxylation-based kinetic resolution of allylic amides were enabled by directly incorporating non-covalentπinteractions between substrates and catalyst,and alkyl substituted allylic amides were obtained with high enantioselectivities（84%-99%ee）at practically useful conversions.