Activation and synthetic transformation of aldehydes and aldehyde equivalents enabled by organocatalysts

• Main Author: Xing, Chong
• Other Authors: Robin Yonggui Chi
• Format: Theses and Dissertations
• Language: English
• Published: 2014
• Subjects: DRNTU::Science::Chemistry::Organic chemistry::Organic synthesis
• Online Access: https://hdl.handle.net/10356/59240
• Institution: Nanyang Technological University

Functionalization of carbonyl compounds has been intensively studied for a long time as carbonyl compounds are commonly used building blocks in organic synthesis. Asymmetric organocatalysis is becoming an increasingly useful approach since its first application in 2000. It is complementary and sometimes better approach to metal catalysis. Different activation modes and catalysts were developed to activate the carbonyl compounds. In this thesis, we tried to use various organocatalysts to activate aldehydes to undergo C-C bond formation reactions. In the second chapter, amine catalysts were used to catalyze the α-alkylation of aldehydes with indole derived diaryl alcohols. Anti-selective products with good yields and enantioselectivities were generated, and their selectivities were opposite to that obtained in literature. Brønsted acids were added as co-catalysts to aid the formation of carbocations. Later, similar acids, as sole catalysts, were found to catalyze the SN1-type alkylation of aldehydes with diaryl alcohols as described in the third chapter. Besides the role to generate the carbocations, acids also accelerated the enolization of aldehydes. Allylic alcohols and α,α-disubstituted aldehydes were effective substrates for this strategy. For the above two reactions, DFT calculations were carried out to support the proposed transition states and reaction pathways. The fourth chapter deals with the activation of carbohydrates as formaldehyde equivalent for the Stetter reaction with chalcones using N-heterocyclic carbene (NHC) catalysis. Carbohydrates such as C6-, C5- and C4-sugars worked well. Among them C5-sugars gave the best results. Paraformaldehyde as formaldehyde precursor was also studied. The Stetter products could be obtained with good yields in both cases.