Direct Oxidative Cross-coupling Reactions Of C(sp~3)-H Bond Via Carbon-Center Free Radical Process

C-H bond directive activation to form C-X(X = O, S, N etc) has recently emerged as the most powerful and straightforward tool for the functionalization of organic molecules in the field of organic synthesis. Aryl sulfides are important building blocks in a wide range of natural products, pharmaceutically active compounds and polymeric materials. With the development of the direct functionalization of C-H bonds, the new stratagem of oxidative cross-coupling between two different nucleophiles in the presence of a proper oxidant is one of the most extensively studied topics during the past ten years, in which utilization of hydrocarbons as the nucleophiles has been considered to be an ideal approach. It’s very interesting to construct C-S bond using this protocol and remarkable progress has been made in the C-S bond formations.Free-radical-initiated sp3-hybridized C-H bond activation received much attention nowadays. The α-position of C-H bond in many stable compounds such as alcohols, ethers, amines and 1,3-dicarbonyl compounds were activated by the radical ion and formed a more usable C-X(X = C, O, N, S) bond. However, the selective activation of the inactive sp3-hybridized C-H bonds in simple alkanes or ethers to generate C-S bonds has remained a challenging task.This project mainly focused on the studies of cheap metal or metal-free catalyzed C-H bond functionalization of cyclic ethers and cycloalkanes to construct C-X(X = S, C, O) bonds. The contents were listed as shown in the following 5 parts:1. This work described the first example of direct C-S bond formation via oxidative thiolation of commercial ethers using di-tert-butyl peroxide(DTBP) as only oxidant under metal-free conditions. A high yielding, efficient, green methodology for the synthesis of alkyl aryl sulfide compounds was developed, moreover, this direct thiolation method is a new protocol for the construction of C-S bonds, which might be very valuable and attractive in sulfur chemistry and radical chemistry.2. A new method for the preparation of alkyl and aryl sulfides through direct oxidative thiolation of alkanes or ethers with arylsulfonyl hydrazide using di-tert-butyl peroxide(DTBP) as oxidant catalyzed by Pd(OAc)2 has been developed. The C-H bond in various alkanes or ethers was successfully converted into C-S bond to yield the e corresponding sulfides in moderate to good yields. This system provides a free-radical pathway for the sp3 C–H activation/C–S bond formation of hydrocarbons and ethers.3. We have developed an efficient transition metal-catalyzed arylthiolation using sodium sulfinates or arenesulfonyl chlorides as sulfur sources. In the presence of 2.0 mol% of metal catalyst and DTBP as an oxidant, a broad range of sodium sulfinates or arenesulfonyl chlorides react with ethers smoothly giving arylthiol substituted ethers in moderate to good yields.This finding offers a new, simple, and mild route for the synthesis of aryl alkyl sulfides via a radical pathway.4. We have developed a novel Cu promoted approach for the synthesis of(E)-β-alkylstyrenes and allylic alcohol derivatives with moderate to good yields through the denitro-coupling reaction of β-nitrostyrenes with benzylic hydrocarbons, ethers, alkanes and alcohols. This method would provide a useful strategy for the synthesis of substituted(E)-β-alkylstyrenes and(E)-allylic alcohol derivatives via the radical addition and denitro-elimination mechanism.5. This thesis describes a new, highly chemoselective Pd-catalyzed procedure for the conversion of sp3 C-H bonds to esters. A wide variety of substrates are readily oxidized under mild and operationally simple reaction conditions. Current studies are focused on further exploration of the substrate scope and synthetic utility of this methodology as well as on probing the mechanism of this transformation. The acetoxylated products are useful building blocks for further synthetic transformations.