The modification of brucine derivatives as chiral ligands and its application in the asymmetric synthesis

<p>The modification of brucine derivatives as chiral ligands and the use of a multifaceted chiral ligand, brucine diol, under different reaction conditions to produce various optical isomers is described. In Chapter 1, the generation of a number of brucine derivatives is described. Taking the advantage of brucine-diol's excellent molecular recognition capability for multiple organic functional groups, we focused on the synthetic modifications of brucine-diol and the synthesis of brucine <em>N</em>-oxide. We also produced various brucine derivatives with different functional moieties in good yields and selectivities. ^ In Chapter 2, we described the investigation of brucine <em>N</em>-oxide catalyzed Morita-Baylis-Hillman (MBH) reaction of alkyl/aryl ketones. Brucine <em>N</em>-oxide was used as a nucleophilic organic catalyst in the MBH reaction of alkyl vinyl ketone. In addition, asymmetric MBH reactions of alkyl vinyl ketones with aldehydes were investigated using a dual catalysis of brucine <em>N</em>-oxide and proline. In this dual catalyst system, proline was found to form iminium intermediates with electron-deficient aryl aldehydes, while the <em>N</em>-oxide activated vinyl ketones provided enolates through the conjugate addition. Our dual catalysis approach also allowed the development of MBH reaction of aryl vinyl ketones.^ In Chapter 3, brucine diol-copper complex catalyzed asymmetric conjugate addition of glycine (ket)imines to nitroalkenes is discussed. Stereodivergent catalytic asymmetric conjugate reactions for glycine (ket)imines with nitroalkenes were achieved using various chiral catalysts derived from a single chiral source, brucine diol. Both <em>syn</em>- and<em>anti</em>-conjugate addition products were obtained with high diastereoselectivity and enantioselectivity. ^ In Chapter 4, enantiodivergent production of <em>endo</em>-pyrrolidines from glycine (ket)imines using brucine diol-copper complex is described. The [3+2] cycloaddition reaction of glycine imines and activated alkenes was performed to produce <em>endo</em>-pyrrolidines. The reversal of enantioselectivity was observed for <em>endo</em>-pyrrolidines between concerted and stepwise reaction pathways.^ The three new brucine derivatives produced in this study would potentially work as organocatalysts and chiral ligands with metal ion in asymmetric synthesis. The brucine diol-metal complex catalyzed reactions laid a good foundation for catalytic asymmetric reactions, where a single chiral source was used to control the absolute and the relative stereochemical outcomes of reactions. Understanding the molecular-level interactions between catalyst and substrates will provide insightful mechanistic details for the stereodivergent approaches in asymmetric catalysis.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Year

2014

Author dc:creator

• Li, Jian-Yuan

Contributors dc:contributor

• Robert Minto
• Haibo Ge
• Mahdi Abu-Omar
• Jonathan Wilker

• Biochemistry
• Chemistry

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/318

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-1411