טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentLevin Anat
SubjectCarbometalation Reactions - An Efficient Tool in Organic
Synthesis
DepartmentDepartment of Chemistry
Supervisor Professor Ilan Marek
Full Thesis textFull thesis text - English Version


Abstract

Carbometalation reaction is one of the key reactions in organic synthesis. Addition of organometallic across unsaturated bond leads to the formation of a new carbon-carbon bond and a new carbon metal bond in a stereodefined manner. In this research we had two targets. The first one was to develp a new approach to the formation of bismetalated cyclopropyl derivatives, and the second was to define the conditions for a regioselective carbometalation reaction of oxygen substituted alkynes.

Bismetalated species was known in the literature since 1971. Gaudemar reported that when allylmagnesium bromide was mixed with zinc or cadmium salts, a transmetalation occurs and the new allylmetal formed can react with vinyl metal to give a bimetallic species. We prepared cyclopropenyllithium from 1,1,2-tribromocyclopropane and added allylmagnesium bromide and zinc bromide. A bismetallic cyclopropane was formed and trapped with different electrophiles. We also showed that this reaction can be diastereoselective, when substituted cyclopropenyllithium species were used. The allylation reaction was proven to be an anti addition by NOE measurement. Enantioselective version of this reaction is under investigation and preliminary results for the enantioselective deprotonation of prochiral cyclopropene substituted with an amide functional group showed excellent enantiomeric excess.

Our second goal, as mentioned above, was to define the conditions for an regioselective carbometalation reaction of oxygen substituted alkynes. Carbocupration reaction is one of the most used reactions. When organocopper reagents are added to α-heterosubstituted alkynes, the directing effect of oxygen is opposite to that of sulfur, phosphorus and silicon substituted alkynes. The former lead to a mixture of regioisomers in a α:β ratio of 47:53 whereas the latter leads only to the α isomers. We found that carbocupration with organocopper derived from dialkylzinc reagent and copper salt gives almost exlusively the β-regioisomer. The scope of the reaction is large since dialkylzinc reagents were prepared in situ from two equivalents of alkylmagnesium halide and one equivalent of zinc salt. The α-regioisomer was formed exclusively when we used ynol ether containing chelating group possessing an additional oxygen atom. In this case the organocopper, prepared from alkylmagnesium halide and copper salt leads to the α-regioisomer whatever the primary, secondary, tertiary and benzyl groups were used.