Asymmetric Catalysis Of Tridentate Bis(Oxazoline) And Bis(Thiazoline)-Lewis Acid Complexes

Chiral tridentate bis(oxazoline) ligands and related bis(thiazoline) ligands are important ligands in the field of asymmetric catalysis. Our research group has developed the diphenylamine-tethered chiral tridentate bis(oxazoline) and bis(thiazoline) ligands. In the past ten years, these ligands have attracted considerable attention. Progresses have been achieved in their application in various important asymmetric transformations by our research group and others. It is believed that these ligands could be applied in other asymmetric transformations. In order to investigate their applications in other types of reactions, we synthesized a series of new substrates, and investigated their catalytic behavior in the use of diphenylamine-tethered bis(oxazoline) and bis(thiazoline) ligands based on our previous work. These ligands were applied in different asymmetric transformations to afford important chiral building blocks and heterocyclic compounds.The diphenylamine-tethered bis(oxazoline)-Zn(OTf)2 complex was applied in the asymmetric Friedel-Crafts alkylation of indoles with nitrodienes. Moderate to good yields with moderate to good enantioselectivities were obtained. In addition, the diphenylamine-tethered bis(oxazoline)-Zn(OTf)2 complex was also used in the asymmetric Friedel-Crafts alkylation of indoles with 2-propargyloxy β-nitrostyrenes. 3-[2-Nitro-1-[2-(2-propyn-1-yloxy)phenyl]ethyl]-1H-indole derivatives were obtained in good to excellent yields with moderate to high enantioselectivities(up to 93% ee). After one step of intramolecular nitrile oxide cycloaddition of the alkylation product, chiral isoxazolobenzoxepane was obtained.An efficient enantioselective tandem Friedel-Crafts alkylation/Michael addition reaction of indoles with nitroolefin enoates was developed by the catalysis of Lewis acid metal complex. The reactions were performed well by addtion of NaOtBu or Et3 N in the presence of the diphenylamine-tethered bis(oxazoline)-Zn(OTf)2 complex. Moderate to high stereoselectivities(up to 95:5 dr, up to 99% ee) and good to excellent yields of the functionalized chiral chromans were obtained.An enantioselective fluorination of β-keto esters/amides was investigated by using the diphenylamine-tethered bis(oxazoline)/bis(thiazoline)-Lewis acid complex. The latter gave better results in the same condition. α-Fluoro β-keto esters/amides were obtained in good to excellent yields with good to excellent enantioselectivities(up to > 99% ee). A catalytic activation mode for the metal catalytic system was hypothesized. The bis(thiazoline)-Cu(OTf)2 complex acts in a bifunctional fashion. The coordinated Lewis acid activates the β-keto ester. Besides, the π–π interaction and NH–O hydrogen bond interaction directs the NFSI attack.A combination of metal catalysis and organocatalysis in asymmetric fluorination of methyl 3-benzylidene-2-oxocyclopentanecarboxylates and Michael addition/intramolecular cyclization of corresponding fluorinated products was also investigated. The reactions were catalyzed by bis(thiazoline)–Cu(OTf)2 complex and quinine-based squaramide catalyst sequentially and afforded chiral 2-amino-3-carbonitrile-7-fluor-tetrahydrocycopenta[b]pyrans in good to excellent yields with good to excellent stereoselectivities(up to 99:1 dr, up to 99.7% ee). Catalytic activation modes for these catalytic systems were hypothesized. The bis(thiazoline)-Cu(OTf)2 complex still acts in a bifunctional fashion on these substrates. The chiral squaramide catalyst activated the(E)-methyl 3-benzylidene-1-fluoro-2-oxocyclopentanecarboxylate through double hydrogen bonding and the tertiary nitrogen of the quinine activated the malononitrile.