The Research On New Methods For The Functional-group Transformations Of Organic Small Molecules

The functional-group transformations of organic small molecules for the construction of high value-added compounds have attracted much attention and extensive study. In particular, the conversions of C=C double bonds, C≡C triple bonds, C-H bonds and C-C bonds have always been the research hotspot in this field. In this thesis, we investigated new reactions and novel methods for the transformations of these functional groups. The main contents and results are listed as following: 1. K2S2O8-Mediated Transformation of Alkene C=C Double Bonds into C=O Double Bonds and C-Br BondsThe K2S2O8-mediated tandem hydroxybromination and oxidation of alkene C=C double bonds with KBr in pure water medium is developed, affording the corresponding phenacyl bromides. A range of substituented styrenes undergo reaction to produce various functionalgroups-containing phenacyl bromide derivatives, and aliphatic alkenes lead to the formation of dibromides as the main products. Based upon experimental observations, a plausible reaction mechanism is proposed. 2. PhI(OCOCF3)2-Mediated Cleavage of Alkyne C≡C Triple Bonds to form C=O Double BondsThe PhI(OCOCF3)2-mediated cleavage of alkyne C≡C triple bonds in alcohol medium is developed under metal-free conditions. In the presence of phenyliodine bis(trifluoroacetate), a diverse range of alkyne and alcohol substrates undergoes triple bond cleavage to produce carboxylic ester motifs in moderate to good yields. The GC-MS trapping experiments and control experiments indicate that the transformation is proposed to proceed via hydroxyethanones and ethanediones as intermediates. Moreover, the reaction exhibits a broad substrate scope and good functional group tolerance. 3. PhI(OAc)2-Mediated Transformation of C(sp2)-H Bonds into C-O BondsThe development of a novel intermolecular oxidative C-H alkoxylation of aniline derivatives is described at ambient temperature. The reaction operates under metal-free conditions with high reaction rates, and gives the aniline para alkoxylation products with high regioselectivity. In the presence of an I(III) oxidant, a range of aldehydes, anilines, and alcohol substrates undergo three-component coupling to produce synthetically useful alkoxylsubstituted N-arylimines. The kinetic isotope experiment implies the C-H bond cleavage of arenes might be involved in the rate-limiting step. Moreover, the control reactions suggest that the C=N double bond is essential for the reaction to proceed efficiently. The preliminary mechanism investigations also revealed that the transformation proceeds via imines as intermediates. 4. NH4I-Catalyzed Transformation of C(sp3)-H Bonds into C-N BondsThe cross-coupling reaction of ketone α-C-H bonds with amine N-H bonds to form C-N bonds is developed using commercially available ammonium iodide as the catalyst and sodium percarbonate as the co-oxidant. A wide range of ketone((hetero)aromatic or nonaromatic ketones) and amine(primary/secondary amines, anilines, or amides) substrates are compatible with the reaction, offering a new method for the synthesis of α-amino ketones that are common structural motifs in pharmaceutical agents and natural products. The utility of the method is highlighted through scale-up reaction and a concise one-step synthesis of the pharmaceutical agent amfepramone. The mechanistic studies indicated that a radical pathway might be involved in the reaction process. 5. Cobalt–Porphyrin-Catalyzed Transformation of C(sp2)-H Bonds into C-C BondsThe cobalt–porphyrin-catalyzed oxidative C-H coupling of phenols to build C-C bonds is developed under mild conditions. In the presence of T(p-OMe)PPCo and Na2CO3, the oxidative coupling of phenols with electron-donating substituents proceeded smoothly with O2 as a terminal oxidant to give the corresponding biaryl compounds in satisfactory yields. The biaryl derivatives are important in the area of pharmaceuticals and as ligands in metal catalysis. On the basis of mechanistic studies, a possible reaction mechanism is proposed. 6. Metalloporphyrin-Catalyzed Transformation of C(sp3)-H Bonds into C=O Double BondsWe report the use of simple metalloporphyrins as a catalyst for the direct oxidation of 2-methoxy-4-methylphenol to vanillin with molecular oxygen under mild conditions. The research results showed that the type of metalloporphyrin used, catalyst loading, temperature, reaction time, the amount of NaOH, solvent, the amount of solvent and the flow rate of oxygen influenced the conversion of 2-methoxy-4-methylphenol and the selectivity of vanillin. Under the optimal conditions, the conversion of 2-methoxy-4-methylphenol was up to 87% and the selectivity of vanillin reached 74%. A possible mechanism was also proposed for the present oxidation on the basis of experimental observations. 7. Copper-Catalyzed Cleavage of C-C(COOH) Bonds to Form C-S BondsA copper-catalyzed oxidative decarboxylative sulfonylation of alkenyl carboxylic acids with sodium sulfinates is developed under an air atmosphere. In the presence of KI, the reaction operates in DMSO with high efficiency. This study offers a new and expedient strategy for stereoselective synthesis of(E)-alkenyl sulfones, and is suitable for various cinnamic acid and sodium sulfinate substrates. Moreover, the mechanistic studies indicate that the transformation is proposed to proceed via a radical process. 8. Iron-Facilitated Cleavage of Two C-C(COOH) Bonds to Form New C-C BondsThe Fe-facilitated decarboxylative cross-coupling reaction between α-oxocarboxylic acids and acrylic acids in aqueous solution is developed. This transformation is characterized by its wide substrate scope and good functional group compatibility, thus providing an efficient and expeditious approach to an important class of α,β-unsaturated carbonyls frequently found in bioactive compounds. Preliminary mechanism studies suggest that a free radical pathway is involved in this process: the generation of an acyl radical from α-oxocarboxylic acid via the excision of carbon dioxide followed by the addition of an acyl radical to the α-position of the double bond in acrylic acid then delivers the α, β-unsaturated carbonyl adduct through the extrusion of another carbon dioxide.