Thiyl Radical Promoted Difunctionallization Of Unsaturated Bonds And Radical Coupling Reactions

After the discovery of the first stable radical, triphenyl methyl radical in 1990, the development of radical reaction was greatly limited due to its high reactivity, uncontrollability and complexity. However recent research showed that radical reaction is predicatable and controllable with advantages over many other reactions. For example,(1) Highly reactive radicals, with good regio-and stereo-selectivity are relatively stable;(2) Many groups can be tolerated in radical reactions;(3) Radical reactions usually take place under mild conditions leading mostly to high yields of product. Hence, over three decades there are more and more researches on radical reactions to be published as more and more researchers turn into this study. It can be predicted that radical reactions will be an important irreplaceable method possessing the characteristics of simple, economical and high efficiency in the near future. This paper focused mainly on radical reactions, specifically its application in organic synthesis. This thesis is divided into two main sections as described below.1. Studies on difunctionalization of unsaturated bonds initiated by thiyl radical.Radical difunctionalization reaction is a type of reaction that introduces simultaneously two different groups unto an unsaturated bond such as a double bond or triple bond. It expands the range of the application of radical reactions, improves reaction efficiency and atom utilization. Hence, radical difunctionalization reaction has been an immediate area of focus in modern organic synthesis. Early studies on the formation of thiyl radical revealed that they can be generated from arylthiols in the presence of t-Bu OOH under air. On this basis, the reaction of thiyl radical with styrenes leading to β?hydroxysul?des was carried out successfully. Furthermore, the difunctionalization of terminal alkynes with thiyl radical leading to α-thioaldehydes was also described. These reactions offered a convenient approach to the aldehyde compounds. Finally, the direct radical acetoxyphosphorylation of styrenes mediated by manganese(III) was also explored,.2. Studies on the radical cross-coupling reactionsAs a significant approach to the formation of carbon-carbon and carbon-heteroatom bonds, radical cross coupling reaction has been extensively studied. After a thorough study of the theory of radical cross coupling reaction, a series of new radical reactions based on 1,3- dicarbonyl compounds have been developed. These reactions are described in the subdivisions below(a) Studies on the bromination of 1, 3-dicarbonyl compoundsBoth 1, 3-dicarbonyl compounds and sodium bromide could be oxidized by manganese(III) to generate carbon radicals and halogen radicals respectively. As a result, radical cross coupling reaction was employed in the design and synthesis of 2-bromo-1,3-dicarbonyl compounds. Further studies showed that mono-brominated products and dibrominated products could be obtained selectively by controlling the amount of the manganese(III). These reactions proved to be a convenient method of synthetizing bromo compounds under mild conditions.(b) Studies on the methylation of 1, 3-dicarbonyl compoundsRecent research has shown that methyl radicals could be generated from tert-butyl peroxybenzoate(TBPB) at high temperature. Meanwhile, the active methylene group of 1,3-diketone compounds can also be oxidized by TBPB to form carbon radicals. The methylation of 1,3-dicarbonyl compounds was carried out successfully by using TBPB as an oxidant and a methyl source at the same time. Compared with traditional methylation, this strategy avoids the use of the toxic iodomethane thus providing a new method of methylation.(c) Studies on the Coupling of Formamides with 1,3-dicarbonyl compoundsIn the presence of di-tert-butyl peroxide(DTBP), N,N-dimethyl formamide(DMF) and 1,3-dicarbonyl compounds can be oxidized to generate acyl radicals and carbon radicals which couples with each other to form amide derivatives. This coupling strategy was also applied to N, N-dialkyl formamide, N-formylmorpholine which are cheap and available substrates towards synthesizing amide compounds. This method is operationally simple giving high yields of product.(d) Studies on the synthesis of 1,2-dicarbonyl compounds from 1,3-dicarbonyl compounds promoted by 2,2,6,6-Tetramethyl-1-piperidinyloxy(TEMPO)TEMPO is a radical species that is stable. As an oxidant, it can also convert methylene of 1,3-dicarbonyl compounds into carbon radicals which is captured again by TEMPO. 1,2-dicarbonyl conpounds is formed after further oxidation, rearrangement, and decarbonylation. This method provides a green, highly efficient, and highly selective approach to 1,2-dicarbonyl compounds.