Some aspects of the chemistry of cyclic aminol ethers
thesisposted on 09.01.2015, 11:38 by Edward P. Sampler
This thesis has been divided into three main sections. The first chapter contains a review of calixarene chemistry, in particular that relating to calix[4)resorcinarenes. Results and discussion are compiled in chapters two through seven and experimental details are provided in chapter eight. Chapters two and three contain results and discussion relating to the novel synthesis of the first example of an enantiomerically pure axially chiral resorcinarene derivative. Chapter two outlines the key step in the reaction sequence, that being the tetramethylation of diastereomerically pure tetrakis(3,4-dihydro-2H-1,3- benzoxazine)calix[4)resorcinarene derivatives. Chapter three describes the subsequent synthetic sequence developed to fragment 3,4-dihydro-2H-1,3- benzoxazines with a view to removing the a-methylbenzylamine chiral auxiliary, which was used to set up the observed axial chirality of the resorcinarene. The sequence incorporates a novel modified Eschweiler-Clarke reaction whereby refluxing the required tetrakis(3,4-dihydro-2H-1 ,3-benzoxazine)calix[4)resorcinarene derivative in aqueous formic acid resulted in reductive ring opening, furnishing the N-methylated analogue. Chapter four describes work on functionalising the 'lower rim' of resorcinarene macrocycles with a view to forming derivatives with a pendant functional group that could be manipulated further to support the newly formed axially chiral resorcinarene derivatives onto solid supports. Chapter five contains prelfminary investigations into the use of axially chiral resorcinarene derivatives as chiral ligands in the enantioselective addition of diethylzinc to benzaldehyde. Chapter six contains results of investigations into the mechanism of the 'RetroMannich' reaction, whereby an amine exchange reaction is observed when refluxing a dihydro-1,3-benzoxazine or Mannich base in a high boiling amine such as morpholine. Evidence has been provided that the reaction proceeds via an o-quinone methide intermediate. Chapter seven describes investigations into the generality of the modified EschweilerClarke reductive ring opening methodology whereby refluxing a formic acid solution of a cyclic aminol ether results in the formation of N,N-dialkyl derivatives via reductive ring opening. It was found that the procedure was general for compounds without sUbstituents at the two position. A second reaction protocol was developed for compounds with substituents at the two position, utilising a combination of sodium cyanoborohydride and chlorotrimethylsilane in acetonitrile to furnish the desired N,Ndialkyl derivatives in excellent yield. Finally, chapter eight contains full experimental details for the synthetic studies carried out in the preceding chapters.