A Study On Design, Synthesis And Applications Of Chiral Diamine Catalysts Based On Natural Amino Acids And Camphor

The rational design, synthesis and application of novel chiral catalyst are always the centre research topic of asymmetric catalysis. The discovery and development of a privileged chiral catalyst can open a new era of asymmetric catalysis variants. This dissertation focused on the design and synthesis of C1-symmetry diamine catalysts with strong asymmetric induction from commercially available cheap chiral starting materials such as natural amino acids and camphor via several steps of general and practical organic synthetic operations and their applications in catalytic asymmetric reactions to access some useful chemical compounds ultimately.First of all, we developed a new synthetic route to the exo-(-)-bornylamine and (+)-(1S,2S,5R)-menthylamine. Then, they were condensed with Cbz-protected proline to construct a small library of chiral secondary diamine ligand. The Henry reaction known as a classic atom-economical carbon-carbon bond-constructing strategy can generate the useful P-nitro alcohol products. So, it was chosen as model reactions to evaluate our novel catalysts performance.3a/CuCl2complex showed outstanding catalytic efficiency for the Henry reaction between a variety of nitroalkanes and aldehydes including aliphatic and aromatic aldehydes. With low to2.5mol%catalyst loading, the reaction proceeded well to afford the desired products in high yields (up to98%) with excellent enantioselectivities (up to99%) and moderate to good diastereoselectivities (up to90:10). With its stable secondary amine moieties, the ligand3a could be recovered by simple aqueous acid/base workup for reuse. This process was air and moisture-tolerant and could be enlarged on10mmol scale without any loss in yield or enantioselectivity. Starting from commercially available3,4-dimethoxybenzaldehyde7j, the corresponding amino alcohol13, a key intermediate for (5)-epinephrine and (S)-norepinephrine, had been successfully obtained. Based on the HRMS and X-ray diffraction analysis of the3a/CuCl2complex, a transition state model was proposed to explain the origin of asymmetric induction.Next, we combined exo-(-)-bornylamine with various substituted imidazole-2-carbaldehydes together followed by reduction in situ to provide a series of stable chiral amino-imidazole ligand. With the assistance of base additive, the ligand15a combined with CuCl2could efficiently promote the Henry reaction in high yields (up to97%) with good enantioselectivities (up to96%).This catalytic system was also suitable for the asymmetric Henry reaction of α,β-unsaturated aldehydes. For the first time, the highly enantioselective Henry reaction of various enals was systematically investigated. There was no1,4-conjugated addition adduct detected in this catalytic system. Under the optimized reaction conditions, the catalytic asymmetric transformation provided the nitro functionalized allylic alcohol adducts with high yields (up to96%) and excellent enantioselectivities (up to99%) for a wide range of substrate scope including acyclic and cyclic α,β-unsaturated aldehydes. Moreover, the product could be readily converted to valuable biologically and pharmaceutically active azatricyclic framework though intramolecular iodocyclization cascade sequence. This methodology represented an alternative synthetic way to access such kind of complex molecules. Additionally, the iodine atom on quaternary carbon position also provided the chances for further derivation.Finally, we condensed the above chiral amine with various primary amino acids to build a group of chiral primary-secondary diamines as organocatalysts to mediate reactions. In combination with acid additive,3f could efficiently promote the Michael addition of nitroalkane to enones with high yields (up to96%) and excellent enantioselectivities (up to98%). As the common advantage of organocatalysis, it did not need the participation of any metal ions. Therefore, it was environmental benign and not sensitive to air or moisture. On the basis of the others previous work and our preliminary experimental results, a possible transition state model was proposed to account for the observed stereochemical outcome.