Font Size: a A A

Synthesis And Application Of New Chiral Phase-Transfer Catalysts In Michael Addition

Posted on:2012-04-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:M Q HuaFull Text:PDF
GTID:1221330362453798Subject:Organic Chemistry
Abstract/Summary:PDF Full Text Request
In past decades, chiral phase-transfer catalysis (PTC) has emerged as an area of intense interest in asymmetric synthesis owing to its operational simplicity and mild reaction conditions. Taking into account these evident advantages, we developed a series of new chiral phase-transfer catalysts and applied them in asymmetric Michael additions. These di/mono-N-spiro quaternary ammonium salts based on the concept of a linker-dictated structure were synthesized conveniently from commercially available optically pure 1,1’-bi-2-naphthol (BINOL).The conformational rigidity and flexibility of a chiral catalyst backbone are the two important factors that influence the steric outcome. The chiral mononuclear quaternary ammonium, drived from cinchona alkaloids or BINOL, had exhabited excellent levels of enantioselectivity for a wide range of asymmetric reactions. However, when the above catalysts engaged in reactions with bucky substrates, only low levels of activation and/or asymmetric induction were demonstrated. In this dissertation, we combine the rigidity and flexibility in design of a range of novel N-spiro quaternary ammonium salts with chiral BINOL backbone. These newly designed catalysts were all confirmed by 1H NMR, 13C NMR and HRMS analyses. Among them, two di-N-spiro quaternary ammonium salts were determined by X-ray diffraction analyses.Herein, a simple and efficient dual enantioselective control in the conjugate addition of , -disubstituted nitromethane toβ-aryl substituted enones can be realized with newly designed dimmers of N-spiro quaternary ammonium salts (1 mol %). Both enantiomers of the adducts can be produced in 43–99% yields with excellent enantioselectivities (up to 99.8% ee) by tuning the linker length of two N-spiro quaternary ammonium salts. More specifically, the asymmetric processe was suited to large-scale synthesis, as well as recovery of the chiral catalysts without loss of activity and stereoselectivity.To date there are no successful examples of direct catalytic asymmetric conjugate additions of glycine imines toβ-aryl substituted Michael acceptors. The steric hindrance of the both reactants may explain the challenge in achieving high diastereo- and enantioselectivity. In this thesis, an efficient, catalytic, diastereo- and enantioselective conjugate addition of N-(diphenylmethylene)glycine tert-butyl ester toβ-aryl substituted enones was realized in the presence of 1 mol % of newly designed N-spiro ammonium salts under mild conditions, affording functionalized -aryl substituted -amino acid derivatives in 57–98% yields with high diastereoselectivity (up to 99:1 dr) and enantioselectivity (up to 93% ee). The adducts are versatile synthetic intermediates and can be readily transformed into highly functionalized 3,5-disubstituted D-proline derivatives and indoline-2-carboxylic acid derivative.Finally, we realized tandem transformations of E-2-Benzylidenebenzo- cycloalkanones with N-(diphenylmethylene)glycine tert-butyl ester in one pot by employment of mono-N-spiro quaternary ammonium salts. A series of benzocyclo- -amino acids were produced in moderate to high yields (57–98%) with high stereoselectivities (up to 93 % ee and 99:1 dr) under mild conditions. The products can simply be transformed into multiple substituted D-proline derivatives.
Keywords/Search Tags:chiral phase-transfer catalyst, β-aryl substituted enone, asymmetric Michael addition, chirality inversion, -amino acid, tandem transformation
PDF Full Text Request
Related items