One-pot tandem reactions for the stereoselective synthesis of functionalised carbocycles

QD Chemistry

Ahmad, Sajjad ; Andrew, Sutherland

University:University of Glasgow

Department:School of Chemistry

关键词: One-Pot, tandem Reactions, Stereoselective, Functionalised Carbocycles;   

Others  :  http://theses.gla.ac.uk/3524/1/2012ahmadphd.pdf

来源: University of Glasgow

【 摘 要 】

A one-pot, two step tandem process involving an Overman rearrangement and a ringclosing metathesis reaction has been utilised for the efficient synthesis of various cyclicallylic trichloroacetamides from simple allylic alcohols. Various methods were theninvestigated for the allylic oxidation of a carbocyclic amide using TBHP along withdifferent transition metals such as Pd, Se, Mn and Cr. This was required for the synthesisof the important building blocks for the construction of structurally diverse antiviral andanticancer carbocyclic nucleosides and natural products.The oxidation of (1S)-N-(cyclohexenyl)trichloroacetamide was then studied leading to thepreparation of two diol analogues in excellent stereoselectivity. The cyclohexenederivative was also stereoselectively functionalised using Upjohn dihydroxylationconditions or by a directed epoxidation/hydrolysis sequence of reactions to generate twoaminocyclitols, the enantiomer of dihydroconduramine C-1 and dihydroconduramine E-1in excellent stereoselectivity.In addition to this, a one-pot tandem process involving a substrate-directed Overmanrearrangement and ring closing metathesis reaction was developed for the stereoselectivesynthesis of a functionalised carbocyclic allylic trichloroacetamide. The functionalisedcarbocyclic amide was employed in the successful synthesis of a syn-(4aS,10bS)-phenanthridone framework using a Pd-catalysed cross-coupling reaction. Stereoselectiveepoxidation and dihydroxylation of the syn-(4aS,10bS)-phenanthridone was theninvestigated leading to the preparation of new analogues of 7-deoxypancratistatin.Attempts were also made to use the functionalised carbocyclic amide in the total synthesisof the Amaryllidaceae alkaloid (+)-γ-lycorane.Further studies were then investigated to expand the scope of the one-pot tandem processto include heterocyclic derived substrates. This led to a seven-membered carbocyclicamide, which has been modified to create a diastereomeric core of balanol.