Hydrogen bonding interactions have been applied to the synthesis of chiral vicinal diamines and the generation of helical chirality. A stereospecific synthesis of vicinal diamines was developed by using the diaza-Cope rearrangement reaction driven by resonance-assisted hydrogen bonds (RAHBs). This process for making a wide variety of chiral diamines requires only a single starting chiral diamine, 1,2-bis(2-hydroxyphenyl)-1,2-diaminoethane (HPEN) and aldehydes. Experimental and computational studies reveal that this process provides one of the simplest and most versatile approaches to preparing chiral vicinal diamines including not only C2 symmetric diaryl and dialkyl diamines but also unsymmetrical alkyl-aryl and aryl-aryl diamines with excellent yields and enantiopurities.
Weak forces affecting kinetics and thermodynamics of the diaza-Cope rearrangement were systematically studied by combining experimental and computational approaches. These forces include hydrogen bonding effects, electronic effects, steric effects, and oxyanion effects.
As an example of tuning diamine catalysts, a vicinal diamine-catalyzed synthesis of warfarin is described. Detailed mechanistic studies lead to a new mechanism involving diimine intermediates. Decreasing the NCCN dihedral angle by varying the diamine structure results in an increase of the enantioselectivity up to 92% ee.
Hydrogen bonds have been used to generate helical chirality in a highly stereospecific manner with a single amino acid and 2,2′-dihydroxybenzophenone. DFT computational and experimental data including circular dichroism (CD), X-ray crystallography and 1H NMR data provide insight into the origin of the stereospecificity. A signalling dizao group can be attached to the receptor for general sensing of amino acid enantiopurity.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/29957 |
| Date | 15 September 2011 |
| Creators | Kim, Hyunwoo |
| Contributors | Chin, Jik |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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