This thesis consists of two major parts:
Part I is about the application of the 1,3-
dipolar cycloaddition reaction in the stereocontrolled synthesis of cyclopropanes; Part II explores the chemistry of gem-dibromocyclopropanes.
Part I:
1,3-Dipolar cycloaddition (1,3-DC) reactions of cyclopropenes to nitrile oxides
gave access to a range of bicyclic systems (i), containing an isoxazoline moiety.
Reduction of those compounds with lithium aluminium hydride afforded amino
cyclopropanol species (ii) with 100 % diastereoselectivity.
Two novel nitrile oxides, one dipole (iii) derived from 2,2-dibromocarboxylic
acid, the other (iv) derived from (S)-(-)-ethyl lactate were prepared. Their asymmetric induction potential and their properties were tested upon reaction with cyclopropenes and acetylenic dipolarophiles.
Catalytic asymmetric 1,3-DC reaction of a nitrile oxide to allyl alcohol provided
enantiomerically pure isoxazoline (v). It served as a precursor for the synthesis of a novel optically active amino cyclopropanol species of type (ii). Transformation of the side chain of isoxazoline (v) was achieved via a Swem oxidation and subsequent Grignard addition.
The scope and generality of the catalytic asymmetric 1,3-DC reaction was
investigated using a range of different substituted allylic alcohols. The catalytic
asymmetric 1,3-DC reaction was also tested upon a nitrile imine.
The syntheses of the strained bicycle (vi) and tricycle (vii) were attempted.
Part II:
Reaction of 2-acyloxymethyl (viii) or 2-acylaminomethyl-1,1-dibromocyclopropanes with methyllithium at -90 °C led to selective bromine-lithium exchange and intramolecular cyclisation to give a l-bromo-3-oxa (ix) or 1-bromo-3-aza-bicyclo[3.l.0]- hexanol with high diasteroselectivity.
Gem-dibromocyclopropanes, derived from the cycloaddition of cyclopropenes to
2,2-dibromocyclopropylformonitrile oxide (iii) were treated with methyllithium at room temperature and it was found that only mono-reduction products were formed.