Synthesis Of Novel Spirocyclic Phosphoric Acid Catalysts And Asymmetric Synthesis Of Chiral Oxazolines Via Kinetic Resolution

Chiral phosphoric acids?CPA?,a type of novel chiral Br?nsted acid catalysts,which exhibit excellent catalytic activities and enantioselectivities in asymmetric C-C bond,C-N bond and other C-heteroatom bond formation reactions,have been recognized as one of the most powerful chiral organocatalysts.Currently,the mostly used chiral scaffolds for chiral phosphoric acid catalysts are BINOL/H₈-BINOL derived ones,and the CPA catalysts derived from SPINOL-type with spirocyclic chirality are also widely used in the field of CPA catalysis.However,the synthesis of these types of CPA catalysts has the disadvantages of tedious synthetic route,low efficiency for chirality availability,and difficulties for further derivatizations.Therefore,it is of great significance to develop an efficient synthesis of a variety of novel chiral spirocyclic phosphoric acid catalysts by the means of asymmetric catalysis.In this dissertation,we designed and synthesized a series of novel spirocyclic phosphoric acids derived from chiral cyclohexyl-fused spirobiindanediol,which were obtained by asymmetric catalysis.We utilized these novel catalysts in the kinetic resolution of 2-amidoallyl alcohols for the asymmetric synthesis of chiral oxazolines,in which the superiority of these novel spirocyclic CPA catalysts has been proved.The main contents of this dissertation include:1)Ir?I?/?S?-t Bu-PHOX ligand was synthesized form?S?-tert-leucine alcohol,which is used as an effective catalyst for asymmetric hydrogenation of 2,6-bis?arylidene?cyclohexanones.Using cyclohexanone and2-bromo-5-methoxybenzaldehyde as starting materials,six steps of condensation,asymmetric hydrogenation,cyclization,methyl coupling,deprotection of methyl ether and ortho-iodination were efficiently performed to provide optically pure 7,7'-iodocyclohexyl-fused spirobiindanediol.By utilizing this common intermediate,Suzuki couplings with different arylboronic acids were achieved to give a series of 7,7'-substittued cyclohexyl-fused spirobiindanediol in good yields.Finally,six new spirocyclic phosphoric acids derived from cyclohexyl-fused spirobiindanediol were obtained through the subsequent phosphorylation and hydrolysis steps.2)Our developed novel chiral spirocyclic phosphoric acid catalysts have been applied in the kinetic resolution of 2-amido allylic tertiary alcohols for the asymmetric synthesis of chiral oxazolines.With the optimal conditions of1 mol%of 7,7'-bis?trifluoromethyl?phenyl substituted cyclohexyl-fused spirocyclic CPA catalyst?2-26f?as the optimal catalyst,toluene as the solvent,and 5?molecular sieve as the additive,we realized the efficient kinetic resolution of a variety of substituted 2-amido allylic tertiary alcohols and asymmetric synthesis of a series of chiral oxazolines with high stereoselectivities,with selectivity factor up to 113.In this work,our study indicated that the cyclohexyl-fused spirocyclic chiral phosphoric acid catalysts possessed superior stereoselectivity than the normal SPINOL type CPA catalyst in these reactions.