Synthesis of 1',2',3',4'-tetrahydro-1,1'-biisoquinoline derivatives and the application in the aldol reaction

• Main Author: Juniwati, Fitri.
• Other Authors: Zaher Judeh
• Format: Final Year Project
• Language: English
• Published: 2010
• Subjects: DRNTU::Engineering::Chemical engineering::Polymers and polymer manufacture; DRNTU::Science::Chemistry::Organic chemistry::Organic synthesis
• Online Access: http://hdl.handle.net/10356/40130
• Institution: Nanyang Technological University

The possibility of catalyzing asymmetric reaction without the use of metal complex, but with purely organic compounds has gained much attention recently. The term “organocatalysts” was thus coined out to describe this new field of the organic chemistry. An example of the organocatalysts is (S)-proline, a widely available amino acid, which was found to be an extremely effective catalyst for the aldol reaction, affording excellent enantioselectivities. The drive to explore alternative potential organocatalysts other than (S)-proline provided the motivation to explore efficiency of 1’,2’,3’,4’-tetrahydro-1,1’-biisoquinoline (BIQ) and its derivatives in the asymmetric aldol reaction. In the first half of the project, BIQ, which functions as a Lewis base, was predicted to follow the enamine catalysis mechanism of the (S)-proline-catalysed aldol reaction, which employs Bronsted acids as co-catalysts. However, chiral BIQ was found to be ineffective when combined with different bronsted acids. This established the enol mechanism of BIQ-catalysed aldol reaction, instead of enamine mechanism. When applying the metal complexes formed by BIQ and Cu(I) Chloride or Cu(I) Bromide in the aldol reaction, a 26% ee of the aldol products, 4-hydroxy-4-(4-nitrophenyl)butan-2-one, was achieved. In the second half of the project, a new Lewis base catalyst based on BIQ and (S)-proline was designed and synthesized. (1’RS)-2’-[(S)-N-pyrrolidine-2-carboxamide]-1’,2’,3’,4’-tetrahydro-1,1’-biisoquinoline was formed by condensing (S)-proline moieties with BIQ scaffold. A 90% de resolution of (1’R)-2’-[(S)-N-pyrrolidine-2-carboxamide]-1’,2’,3’,4’-tetrahydro-1,1’-biisoquinoline was also obtained in this project. Although the new catalyst has not been applied to the asymmetric aldol reaction, it is predicted to give better selectivity of the aldol products in comparison to the BIQ scaffold.