טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentMaksymenko Shimon
SubjectDevelopment and Application of Umpolung ALPHA-Arylation
of Carbonyl Compounds
DepartmentDepartment of Chemistry
Supervisors Professor Yoav Eichen
Professor Alex.m Szpilman
Full Thesis textFull thesis text - English Version


Abstract

Novel transition metal free arylation and heteroarylation reactions of ketones, have been designed, developed and studied. These transformations, exploiting a two-step synthetic strategy, are based on umpolung of the α-carbon of carbonyl compound. At the first step a semi-stable electrophilic enolonium species is prepared at low temperature from a silyl enol ether using hydroxy(tosyloxy)iodobenzene (commercially available Koser’s reagent), which belongs to a class of λ3-iodanes. At the second step a nucleophile undergoes addition to the α position of the electrophilic enolonium species, affording the substituted carbonyl compound.

            Ketones, possessing primary and secondary α-carbons substituents, and 1,3-dicarbonyl compounds were found to be appropriate precursors for these highly electrophilic enolonium species. A wide range of nucleophiles: arenes, heteroarenes, silyl enol ethers and TMS-azide successfully couple with enolonium species. The reactions of enolonium species with arenes, result in the formation of C-C bonds, affording yields of up to 83% of the α-aryl ketone. The reactions of enolonium species with aza-arenes, result in formation of C-N bonds, affording the α-N-heteroaryl ketone. In all the cases, only mono-arylated products were obtained. The reactions of enolonium species with TMS-azide, result in formation of C-N bonds, affording yields of up to 88% of the α-azido ketone. The reactions of enolonium species with TMS-enol ethers afford unsymmetrical 1,4-ketones in yields of up to 74%. A probable mechanism of the electrophilic addition to arenes has been suggested based on analysis of the reaction outcome. The configurational stability of enolonium species has been demonstrated.