PartI. Site-Selective Geminal Chlorofluorination of α-Keto Thioesters, PartII. Study on Stereoinvertive Deoxygenation of Tertiary Alcohols via Dioxaphospholene

Abstract

Part I. The construction of a carbon center with two different halogen substituents is significant for synthetic chemistry. Recently, our group utilized dioxaphospholene with a non-dealkylatable phosphoramidite for geminal chlorofluorination of 1,2-diketones. However, poor site selectivity with unsymmetrical 1,2-diketones was still a problem caused by the similar reactivities of the two carbonyl groups. α-Keto amide and α-keto ester were rational candidates containing two distinguishable carbonyl groups, but our previous works found both types of substrate were problematic even for the formation of dioxaphospholene. α-Keto thioester was found suitable and provided high site-selectivity for geminal interhalogenation, which was rationalized based on the anion-stabilization effect by an adjacent sulfur atom. Based on the formation of fluorophosphoramidate and starting material as side products, two competing side reaction pathways involving the SN2 mechanism were proposed. The phosphoramidite was altered into various non-oxygenated phosphorus(III) reagents to prevent dealkylation. Moreover, the steric effect on the phosphorus center was examined for the prevention of starting material regeneration. Also, a series of Lewis acids were used for the selective acceleration of the desired SN2 process. Part II. Whereas deoxygenation of alcohols has been extensively explored, it is still problematic to be utilized for the stereospecific reduction of tertiary alcohols. In this dissertation, a reduction of silyl-protected tertiary alcohols was studied via dioxaphospholane. In the presence of hydrogen fluoride reagents, the α-silyloxy-dioxaphospholene was deoxygenated to give tertiary alkane. The combination of proton and fluoride sources was found to be crucial. The effect from the various HF reagents was studied and rationalized based on the pKa values of proton sources and the reactivity of the counterion. Also, the deoxygenation mechanism was suggested to be initiated by the protonation of a dioxaphospholene intermediate, followed by a 1,2-hydride shift extruding the oxygen atom.