Free radical cyclisation of imines
thesisposted on 2014-07-28, 12:05 authored by Adrian R. Young
Introduction. The free radical cyclisation reaction onto an unsaturated bond is a well known synthetic pathway, where a wide range of cyclic compounds can be produced form acyclic starting materials. Up until recent years, free radical addition to multiple bonds other than carbon-carbon had been little studied. Nowadays there is much information available of radical addition to carbonyl, thiocarbonyl, nitrile and oxime ether (C=NOR) functional groups. However there has been surprisingly little detailed study of similar reactions involving imines (C=NR) or hydrazones (C=NNHR). Monocyclisation. In the early phase of the research, different types of imine were synthesised and subjected to the standard free radical cyclisation procedure (tributyl-tin hydride / AIBN, added by syringe pump to refluxing solvent) to determination of the regiochemistry of cyclisation onto imines and to assess the synthetic potential of the reaction. The results of this investigative study show that a variety of five and six-membered ring compounds can be synthesised in good yield. A similar study of hydrazones showed that fivemembered rings can be formed under the same reaction conditions. Tandem Reactions. In the next phase, the aim was to extend the methodology to produce more complex structures from acyclic starting materials. If a radical adds to the carbon atom of an imine, a nitrogen-centred (aminyl) radical is generated which can undergo subsequent addition to a suitably positioned double bond to yield a bicyclic amine. This type of reaction is known as tandem or cascade cyclisation. By this method, compounds could be synthesised which have similar structures to natural products. A range of suitably designed imines wct.5. prepared and underwent cyclisation, producing many different types of bicyclic amine in yields varying from moderate to good. The Synthesis of Natural Products. After the successful formation of key bicyclic structures, the third phase of the research aimed at the synthesis of one or more of target natural products. The synthetic strategy used in the tandem reactions outline above was. adapted for these purposes. However the synthesis of the desired compounds could not be achieved in the time, but progress towards their formation was achieved.