טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentArava Shlomy
SubjectNovel Design and Application of Enolonium Species
DepartmentDepartment of Chemistry
Supervisors Professor Yoav Eichen
Professor Alex.m Szpilman
Full Thesis textFull thesis text - English Version


Abstract

Enolonium species/iodo(III)enolates of carbonyl compounds have been suggested to be intermediates in a wide variety of hypervalent iodine induced chemical transformations of ketones, including α-C-O, α-C-N, α-C-C and α -carbon-halide bond formation, but they have never been characterized. This work is showing the preparation, first characterization, and identification of Enolonium Species. First, we have found specific conditions which allowed us to conduct spectroscopic characterization of Enolonium Species using NMR and IR techniques. Our observations strongly indicate that the major or only hypervalent iodine species present in these Umpolung reactions is the enolate-oxygen-bound hypervalent iodine species rather than the α-C-bound hypervalent iodine species. Later we have showed that these Enolonium Species are direct intermediates in oxygenation, amination, chlorination and enol dimerization. These findings allowed us and others to study and design new reactions and applications involving Enolonium Species. Particularly, these findings led us to develop a novel two-step strategy in which the Enolonium Species is formed as a discrete intermediate in one step followed by cross coupling with nucleophiles in a second step. Based on this two-step strategy, we have intensively explored and developed a new Umpolung α-allylation reactions. This novel strategy breaks the limitations of classical chemistry in which ketone enolates react at the less sterically hindered position with unsymmetrical allylating reagents. We have showed the ability of Enolonium Species to react with prenyl, crotyl, cinnamyl, and allyl silanes along with absolute regioselectivity in up to 92% yield.

As a second part of our research we have studied and developed the new concept of Umpolung Morita-Baylis-Hillman reaction via the formation of Enolonium Species. The classical reaction of unsaturated ketones and aldehydes with tertiary amines catalysts is known as the Morita-Baylis-Hillman (MBH) reaction. This thoroughly investigated reaction proceeds through the formation of a nucleophilic MBH intermediate followed by reaction with an electrophilic species. Accordingly, we have showed that nucleophilic MBH intermediate can be made to react with an hypervalent iodine reagent to form a new electrophilic MBH intermediate which, in turn goes through cross coupling nucleophilic substitution. First, we had to overcome the challenges involving the compatibility of the amine reagent with oxidizing hypervalent iodine. Then, we applied this concept in several C-O bond forming reactions including α-tosylation, α-triflation, and α-acetoxylation. In the case of the α-acetoxylation reaction we have further demonstrated the conversion of the α-acetoxylated product to the 1,2-diones. Interestingly, the Umpolung MBH reaction was found to be compatible with introducing nucleophiles other than iodane-ligated nucleophiles. Thus, it was demonstrated that α-tosylation of various α-β unsaturated ketones took place in up to 80% yield took place when using PIDA as the oxidant and para-toluenesulfonate pyridinium (PPTS) as the source of toslyate nucleophile.