Manganese Catalyzed Selective C(sp3)-H Bond Halogenations

Abstract

During the past three decades, manganese porphyrins and related Schiff bases have received considerable scrutiny due to their high reactivity toward functionalization of both unsaturated and saturated hydrocarbons. However, most of this work dealt with oxygenation reactions, particularly olefins epoxidation and C-H bonds hydroxylation. Only few reactions involving the catalytic incorporation of other groups, including chlorine, bromine, iodine and azide, have been achieved. On the other hand, halogenated organic compounds, including organochlorine and organofluorine molecules, play a very crucial role in organic chemistry, affording important components of a variety of biologically active molecules as well as pharmaceutical agents. Accordingly, the development of new chemoselective and regioselective approaches to the synthesis of alkyl halides remains an important challenge. In this dissertation, we will demonstrate several novel selective sp3 C-H bonds halogenations catalyzed by manganese complexes.

In chapter 1, current studies on the functions and mechanisms of cytochrome P450s and metalloporphyrins are reviewed. The development of iron and manganese porphyrins catalyzed oxygenation reactions as well as the characterizations of important intermediates responsible for oxygen transfer, including oxoFeIV porpyrin cation radicals and oxoMnV porphyrin species, has also been reviewed. In chapter 2, we report a manganese porphyrin catalyzed selective aliphatic C-H chlorination reaction. This new chlorination system can be applied to simple hydrocarbons and complex substrates. In chapter 3, we report a manganese porphyrin catalyzed selective aliphatic C-H bonds fluorination reactions. The new fluorination system can be applied to different alkanes, terpenoids and steroids. Mechanistic studies implicate a manganese difluoride intermediate that reacts with alkyl fluoride radicals generated by an oxoMnV. In chapter 4, we report a manganese salen catalyzed reaction for the formation of benzylic fluorides directly from C-H bonds. This reaction does not require a directing group and uses simple and easily handled nucleophilic fluoride reagents. The success of this direct C-H fluorination reaction suggests a general strategy for late stage drug diversification and building block construction.