New one-pot multi-reaction processes for the synthesis of highly functionalised carbocycles and heterocycles

QD Chemistry

Grafton, Mark W. ; Sutherland, Andrew

University:University of Glasgow

Department:School of Chemistry

关键词: One-Pot reactions, Overman rearrangement, Enyne metathesis, Diels-Alder reaction, tandem catalysis, natural product synthesis;   

Others  :  http://theses.gla.ac.uk/5864/1/2014graftonphd.pdf

来源: University of Glasgow

【 摘 要 】

With the use of a one-pot process, a diastereoselective synthesis of bicyclononanes and decanes has been developed. Initial treatment of an allylic alcohol with trichloroacetonitrile, in the presence of DBU, afforded the corresponding allylic trichloroacetimidate. The trichloroacetimidate was then subjected to a one-pot processinvolving a thermal Overman rearrangement, ring-closing-enyne-metathesis and a hydrogen-bond directed Diels-Alder reaction to form polycyclic products in good isolatedyields and as single diastereomers.Research was then carried out on how this process could be extended. Through the use of Grubbs second generation catalyst, the process was extended to include a cross-metathesis reaction forming highly functionalised 1,3-dienes. These 1,3-dienes were then used in the hydrogen bond directing Diels-Alder reaction to generate highly functionalised polycycles,again as single diastereomers. This process was then employed towards the first total synthesis of the natural product, netamine A. Further studies showed that carbo- and heterocyclic 1,3-dienes could be used in a one-pot Diels-Alder reaction and aromatisation step for the rapid preparation of partially saturated indane and tetralin motifs, which are present in biologically active molecules.