i) Design and Synthesis of Butadiene Substrates for Organocatalytic Transformations ii) Synthesis of Functionalized Biaryls and Pyran Derivatives

This thesis details the exploration of a number of discrete but interlinked projects. 1) The synthesis of 1,3-bis-subsitituted electron-deficient butadiene substrates for the study of vinylogous Michael-type addition chemistry through organocatalytic means. The synthesis of these electron-deficient butadienic systems proved to be quite challenging and required extensive reaction screening in order to access these substrates in synthetically useful scales. A modular approach to diene synthesis was developed in order to gain access to distinct butadiene families through the combination of aryl formyl acrylonitriles and stabilized ylides in a base-free Wittig olefination reaction. The use of the polymerization inhibitor 8 hydroxyquinoline was found to be key to the synthesis of these challenging substrates to prevent the vinyl nitriles from polymerizing. Density Functional Theory (DFT) calculations were also performed on the butadiene substrates in order to develop a better understanding of the conformations and geometries the butadienes adopt, a key part of their potential reactivity. 2) The study of these newly synthesized butadienes in an asymmetric organocatalytic 1,6-conjugate addition/cyclization to yield enantioenriched cyclic hexadienes did not yield the expected products and instead yielded densely functionalized biaryl species which are of some synthetic interest. Our attentions were then turned to the directed synthesis of these biaryls. This was accomplished through the use of stoichiometric quantities of piperidine in order to reduce the potential for polymerization or side-reactions which would consume the starting material. A study into the aromatization of the cyclic hexadienes into the biaryl species was also carried out. A crystal structure of one of the biaryl species 125 was also elucidated which unambiguously confirmed the structure of the biaryls. 3) A key synthetic intermediate in the synthesis of the 1,3-bis-subsitituted butadienes was the aryl formyl acrylonitriles. This class of compounds has been little studied and a number of interesting reactivities that they exhibit were discovered during the attempted syntheses of butadienes. The final part of this thesis details the synthesis of 2-amino-4H-pyrans from the conjugate addition of malononitrile to aryl formyl acrylonitriles and the synthesis of 3,4 dihydro-2H-pyrans through Inverse Electron Demand Hetero-Diels-Alder (IEDHDA) cycloaddition reactions. An asymmetric variant of the synthesis of 2-amino-4H-pyrans was attempted. In depth discussion on the regio- and stereoselectivity of the IEDHDA is also given and supported by detailed NMR analysis.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

National University of Ireland Maynooth

Year dc:date.issued

2017

Author dc:creator

• Driver, Ross B.

Language dc:language

en