Development of transition metal-catalyzed C-S and C-C cross-coupling reactions

Abstract

The transition-metal-catalyzed carbon-carbon and carbon-heteroatom bond forming reactions are important and fundamental transformations in synthetic organic chemistry. These reactions have been widely used for a variety of cross-coupling reactions of aryl halides in the processes of C?C, C?N and C?S bond forming reactions. In this dissertation, we have developed new cross-coupling protocols for the synthesis of vinyl sulfides, benzothiazoles and benzoxazoles, using transition-metal-based catalysis. Furthermore, the mechanism of these cross-coupling reactions has also been investigated.

Although numerous methods have been developed for the stereoselective synthesis of (E)-vinyl sulfides, it has been challenging to prepare Z-isomers. Chapter 2 describes a novel method for the synthesis of vinyl sulfides by the decarboxylative cross-coupling of arylpropiolic acids with thiols using copper(I) salts as catalysts. In the presence of CuI and Cs2CO3, a number of thiols reacted with arylpropiolic acids to afford the corresponding vinyl sulfides in high yields with high stereoselectivity for Z-isomers. This work suggests the potential for broad generality and promotes an economically feasible route to large scale synthesis of vinyl sulfides without the need of organohalide reagents.

Chapter 3 deals a general and highly efficient method for direct thiolation of heterocyclic C?H bond with thiols. Without the need of organohalide precursors, a variety of 2-thio-substituted benzothiazoles, imidazoles and indoles are synthesized in one step in the presence of CuI, 2,2'-bipyridine, and Na2CO3. Both aliphatic and aromatic thiols are compatible with this method, resulting in the formation of corresponding cross-coupling heterocycles in good yields. In addition, we present detailed mechanistic investigations on the Cu(I)-mediated direct thiolation reactions. Both computational studies and experimenta results reveal that the copper-thiolate complex [(L)Cu(SR)] (L: nitrogen-based bidentate ligand such as 2,2'-bipyridine; R: aryl or alkyl group) is the first reactive intermediate responsible for the observed organic transformation. Furthermore, our computational studies suggest a stepwise reaction mechanism based on a hydrogen atom abstraction pathway, which is more energetically feasible than many other possible pathways including ?-hydride elimination, single electron transfer, hydrogen atom transfer, oxidative addition/reductive elimination and s-bond metathesis.

A new transition metal-catalyzed C?C bond-forming reaction between benzothiazoles (or benzoxazoles) and arylboronic acids is presented in Chapter 4. This new method provides a simple means to access aryl-substituted benzothiazole and benzoxazole compounds, a task that otherwise requires several synthetic steps or harsh reaction conditions.

Besides my main project on homogeneous catalysis, we have also studied the nanoparticle-based catalysis reactions. The synthesis and catalytic studies of novel palladium nanostructures assembled from small nanoparticles by a surfactant-templated method are described in Chapter 5. The nanomaterials were characterized by several techniques including XRD, SEM, and HRTEM, which reveal that these one-dimensional nanomaterials comprise high density nanocontacts of ~1 nm in contact length at the particle?particle interface. In contrast to palladium nanoparticles, the palladium nanowires exhibit enhanced catalytic activities towards C?C cross-coupling (e.g., Suzuki and Heck couplings) reactions under mild conditions. The recyclability of the nanowires for catalytic reactions has also examined and it has found that the catalysts exhibit essentially unaltered catalytic activity (~ 99%) over six recycles.