| dc.description.abstracteng | Transition metal-catalyzed cross-coupling reaction as one of the greatest chemical innovations of 20th century has to utilize stoichiometric amounts of prefunctionalized reagents. In comparison, the transition metal-catalyzed direct C–H functionalization provided a more atom- and step-economical pathway for the synthesis and modification of arenes. Within this thesis, several new synthetic methods based on transition metal-catalyzed C–H functionalization have been developed.
Oxidative annulations of alkynes by C–H/N–H cleavages have recently emerged as a useful strategy for the sustainable preparation of N-heterocycles. To avoid the use of excess amounts of sacrificial oxidants, transition metal-catalyzed C–H/N–O bond functionalizations with N-substituted benzamides have been investigated. In the first project, a novel isoquinolone synthesis has been achieved utilizing ruthenium(II)-catalyzed C–H/N–O functionalization. This green approach employed H2O as the reaction medium, and generated H2O as the sole byproduct. The catalytic system also proved applicable for oxidative alkenylations.
The carboxylate-assisted C–H bond founctionalization was also investigated. Various carboxylate additives were probed, of which the electron-deficient carboxylate 3-(F3C)C6H4CO2K was found to be the optimal additive for the ruthenium(II)-catalyzed C–H/N–O functionalization in water. Due to the different effects of carboxylates, next generation ruthenium(II) carboxylate catalysts should be designed and synthesized specifically for different novel transformations.
The second project refers to ruthenium(II)-catalyzed C–H oxygenations on synthetically useful Weinreb amides. With hypervalent iodine(III) reagent PhI(OAc)2 as the oxidant, the ortho-selective C–O formation efficiently took place at a reaction temperature of 50 °C, which should be the lowest reaction temperature reported thus far for ruthenium(II)-catalyzed C(sp2)–H bond oxygenations.
Furthermore, the practical importance of C–H bond oxygenations on aryl Weinreb amides was illustrated by the high-yielding preparation of the corresponding salicylaldehyde.
A more atom- and step-economical pathway for salicylaldehyde synthesis would directly start from benzaldehyde, representing a challenging project. The intra- and intermolecular competition experiments between different carbonyl group-containing substrates showed aldehydes to be the weakest directing group so far. Meanwhile, aldehyde has the inherent tendency to be readily oxidized to the corresponding acid. Utilizing the unique catalytic activity of [RuCl2(p-cymene)]2, we successfully accomplished the chelation-directed ortho-oxygenation on benzaldehydes with PhI(OTFA)2 as the oxidant. The use of molecular O2 in the ruthenium-catalyzed ortho-oxygenation on benzaldehydes will be the highest level in this field.
Salicylaldehydes are useful starting materials in the synthesis of many natural products. We explored the unique utility of the formyl group for the late-stage diversification.
Despite the tremendous achievements during recent years, transition metal-catalyzed direct C–H functionalizations have been somewhat limited because of the commonly used high reaction temperatures. Thus in the fourth project, we turned to photo-catalysis. Various heteroarenes as well as natural products were synthesized utilizing photo-induced copper(I)-catalyzed C–H arylations at ambient temperature. Non-aromatic oxazolines were also viable substrates in this C–H arylation reaction. Visible light catalysis was also probed with thus far somewhat limited success.
Photo-induced transition metal-catalyzed C–H functionalizations have provided a charming future for the facile synthesis of tremendous compounds and materials which cannot be achieved by thermal synthesis. I would suppose great development in this field with various transition metals, photo reagents, as well as irradiation sources. | de |