Organocatalytic Asymmetric Reactions To Construct3-Monofluoromethyl-3-Arylpropanoic Esters And Chiral Hetero-Quaternary Stereogenic Centers

(一) Organocatalytic Asymmetric Reactions to Construct3-Monofluoromethyl-3-Arylpropanoic Esters1. Asymmetric Decarboxylative1,4-Addition of Malonic Acid Half Thioesters to Vinyl Sulfones: Highly Enantioselective Synthesis of3-Monofluoromethyl-3-Arylpropanoic EstersAn asymmetric decarboxylative1,4-addition of malonic acid half thioesters (MAHTs) to2-aryl-substituted vinyl sulfones was developed with excellent enantioselectivity (up to97%ee). In view of tuning pKa values, a quinine-based benzyl-substituted thiourea was designed and demonstrated as the most efficient catalyst. The enantioselective synthesis of3-monofluorinated analogues of3-methyl indanone and (+)-turmerone has been accomplished from decarboxylative1,4-addition adducts with satisfactory results2. Organocatalytic Asymmetric Michael Addition of5H-Oxazol-4-Ones to Vinyl Sulfones:Highly Stereoselective Synthesis of2-Alkyl-2-Hydroxy-3-Monofluoromethyl-3-Arylpropanoic EstersAn organocatalytic asymmetric Michael addition of5H-oxazol-4-ones to2-aryl-substituted vinyl sulfones has been successfully developed. From the Michael adducts, important2-alkyl-2-hydroxy-3-monofluoromethyl-3-arylpropanoic esters which are the precursors or building blocks of many bioactive compounds, can be conveniently prepared. Difficulties of this research is the construction of two chiral centers, reaction using hydrogen induced allylic sulfone; the advantages of the study is low dosage of catalyst (1-10mol%), simple processing (filtering), and may be suitable for industrial production. The experimental results demonstrated the importance of the weak non-classical C-H…O hydrogen bonding interaction between the oxazols and the thiourea catalyst in increasingrat enantioselectivity. (二) Organocatalytic Asymmetric Reactions to Construct Chiral Hetero-Quaternary Stereogenic Centers1. Organocatalytic Asymmetric Michael Addition of5H-Oxazol-4-Ones to NitroolefinsThe first organocatalytic asymmetric Michael addition of5H-oxazol-4-ones to nitroolefins has been developed. In the presence of easily prepared L-tert-leucine-derived tertiary amine/thiourea catalyst, the Michael addition of5H-oxazol-4-ones to nitroolefins proceeded in excellent diastereo-and enantioselective manner (up to99%ee and>19:1dr). The Michael adducts obtained are valuable precursors for the synthesis of chiral α-alkyl-α-hydroxycarboxylic acid derivatives, which represent a series of versatile building blocks in many biologically active compounds.2. Highly Enantioselective Organocatalytic α-Sulfenylation of AzlactonesThe first asymmetric α-sulfenylation of azlactones with N-(sulfanyl) succinimides has been developed by using cinchona alkaloid-derived squaramide as catalyst and4A molecular sieves as additive. The reaction conditions were suitable to4-alkyl and benzyl-substituted azlactones as well as N-(benzyl/alkyl/arylthio) succinimides, affording adducts with high enantioselectivities (81-94%ee). 3. Highly Enantioselective α-Sulfenylation of5H-Oxazol-4-Ones to N-(sulfanyl) succinimidesAn unprecedented asymmetric α-sulfenylation of5H-oxazol-4-ones with various N-(sulfanyl) succinimides has been developed by utilizing a cinchona alkaloid-derived squaramide as catalyst. A series of α-sulfenylation adducts were obtained with good to excellent enantioselectivities (86-95%ee), representing the first example of catalytic asymmetric construction of the biologically important α-sulfur-substituted α-hydroxy carboxylic acid derivatives.