CO2-Mediated Synthesis of Sulfoxides and Disulfide

Chapter 1 serves the utility of CO2 and sulfur (sulfoxide (IV) and disulfide (I)) in organic synthesis and the catalytic asymmetric oxidation. CO2 plays a range of roles in the promoted reactions, such as assisting in leaving hydroxyl groups, forming directing groups, Lewis acid, Brønsted acid, and a temporary protecting group. The general synthetic methods of sulfoxides and disulfides and their applications in biology, medicine, materials, industrial chemistry, and etc. are introduced in detail. Especially sulfinyl and disulfide moieties played an important role in the application. Asymmetric catalytic oxidation of C=C bonds and sulfides has yielded highly efficient results in both metal catalysis and organocatalysis. However, the development of low-toxic, inexpensive and efficient organic catalysts remains a major challenge for chemists. Chapter 2 presents an unprecedented in-situ generations of sulfenate anions via Michael addition and acrylonitrile elimination from vinyl sulfoxides. Subsequently, the reaction of a sulfenate intermediate with the C1 building block methylene chloride yields a versatile synthon, chloromethyl sulfoxide. We are also looking forward to the asymmetric synthesis of chloromethyl sulfoxide through our strategy. Chapter 3 demonstrates an unprecedented CO2 and cyanide-mediated transformation of vinyl sulfoxide through Pummerer rearrangement. We found that sulfoxides (sulfur (IV)) were transformed to the corresponding symmetrical disulfides (sulfur (I)) products under CO2 atmospheres with moderate to high yields, while trace amounts of products were detected with the control experiments under other atmosphere (O2, H2, N2 and air). When studying the reaction mechanism, we found the significant decomposition of starting materials and products in the absence of CO2. The plausible mechanism was further certified by a crossover experiment and a radical trapping reagent. Chapter 4 describes a CO2-mediated selective oxidation of sulfide. In the presence of carbon dioxide, hydrogen peroxide underwent an umpolung in-situ formation of the V electrophilic oxidant, peroxymonocarbonate, whereby the corresponding sulfoxide can be obtained from oxidation of sulfide with high selectivity. Meanwhile, the pKa of the bases played a critical role in the reaction. In addition, we expect to find a suitable chiral amine to achieve CO2-mediated asymmetric oxidative synthesis of sulfoxides under the reference of pka. Chapter 5 describes the first total synthesis of (−)-dithiosilvatin. This product, which has the opposite specific rotation compared to the natural product, was obtained in nine steps and 24% yield using abundant Boc-L-tyrosine methyl ester as the starting material. In a key step, BBr3 was used to both deprotect two sulfur ethers and induce an efficient epimerization to the needed cis-configuration of the two sulfur atoms while enantiomeric ratio preserved, possibly via formation of a stable cyclic S–B–S intermediate. The disulfide bridge ring closure and the isoprenylation was accomplished in one pot under Mitsunobu reaction. The Mitsunobu reaction-based strategy provided a protocol for the total synthesis of specific epi- dithiodiketopiperazines (ETPs), especially those containing a methine carbon at C3 and a prenyloxy substituent on the aromatic side cha