Novel Applications of Benziodoxole Reagents in the Synthesis of Organofluorine Compounds

Distributor: Department of Organic Chemistry iii " Knowing without seeing is at the heart of chemistry. " – Roald Hoffman iv v Abstract This thesis concerns method development of new synthetic routes by applying electrophilic hypervalent iodine reagents, such as trifluoromethyl-benziodoxole (Togni reagent) and fluoro-benziodoxole. The first project involved the addition of an oxygen moiety and trifluoromethyl group across double and triple bonds (both groups derived from the hypervalent iodine reagent). We observed that electron donating substituents on the aromatic ring of the substrate accelerated the oxytrifluoromethylation reaction. This transformation was further expanded to halo-trifluoromethylation reaction of a vinyl silane substrate. We also developed a copper mediated cyanotrifluoromethylation reaction, which was accelerated by PCy 3 additive. This transformation allowed for the creation of two new CC bonds in a single addition reaction. The direct C-H trifluoromethylation reaction of quinones was achived using the Togni-reagent in the presence of B 2 pin 2 additive. The intriguing additive effects of both B 2 pin 2 and PCy 3 inspired us to examine the mechanism of these transformations. Fluoro-benziodoxole is the fluoroiodane analogue of the trifluoromethylating Togni reagent. We developed a AgBF 4 mediated geminal difluorination of styrenes using this fluoroiodine reagent. In this process one fluorine atom came from the fluoroiodane, while the other fluorine was derived from the tetrafluoroborate ion. A similar approach was applied for the 1,3-oxyfluorination and difluorination of cyclopropanes. Similarly, this fluorinative ring opening of unactivated cyclopropanes involved the introduction of an electrophilic fluorine atom from the fluoroiodane reagent and a nucleophilic one from the tetrafluoroborate ion. This reaction was extended to synthesis of 1,3-oxyfluorinated products. When alkenes reacted with the fluoro-benziodoxole reagent in the presence of palladium catalyst the iodofluorination reaction occurred. Both the iodine and fluorine atoms were derived from the fluoroiodane reagent. The iodofluorination reaction with disubstituted and cyclic alkenes proceeded with high regio-and stereoselectivity. This thesis is based on a licentiate thesis by Nadia O. Ilchenko entitled " Development of catalytic electrophilic trifluoromethylation and fluorination methods " and the following papers, referred to in text by their Roman numerals I-VII. Reprints were made with kind permission from the publishers. x xi Abbreviations Abbreviations are used in agreement with standards of the subject. # Additional non-standard or unconventional abbreviations that appear in this thesis are listed below. Yields given in paranthesis were determined by NMR, all other yields were reported as isolated. BQ 1,4-benzoquinone CAN …