Methodological Study Of DDQ-mediated Cross-Dehydrogenative Coupling Reaction

As one of the most important part of modern organic synthesis, developing efficient and atom economic C-C bond formation methods is always of most interest for chemists. Among them, transition metal catalytic coupling reaction, represented by Suzuki, Negishi, Heck reactions, is the most successful example. However, the recent emerged cross-dehydrogenative coupling (CDC) provides undoubtedly a more efficient strategy for C-C bond formation. It has many advantages such as simple operation, mild condition, cheap materials and high atom economy.2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), which usually is applicated in CDC raction as hydrogen acceptor, is proved to be of high value.Inspired by the ideas in (hetero)polycyclic skeleton formation, we take cross-dehydrogenative coupling as the basic strategy to carry out a series of new synthetic methodological studies in (hetero)polycyclic skeleton formation, which may of great potential for application. Our work mainly includes three aspects as below.1. DDQ-mediated dyhrogenation of benzothiazole derivativesOn the base of our prior study in synthetic methodological studies of benzothiazole derivatives, DDQ was used as a dehydrogenative reagent in dehydrogenation of benzothiazole derivatives, which was proved to be a mild and efficient methold for the synthesis of unsaturated ester.2. DDQ-mediated activation of sp3 C-H bonds adjacent to heteratomsTaking DDQ-mediated activation of sp3 C-H bonds adjacent to heteratoms and restulted intramolecular CDC reaction as the strategy, we obtained a series of benzophenone derivatives from phenethyl benzyl ethers through DDQ-oxidation followed by intramoleculer Friedel-Crafts type reaction. This reaction needs no catalyst and has high regioselectivity, which leads a new way to the regioselective synthesis of benzophenone derivatives.3. DDQ-mediated activation of benzylic and allylic sp3 C-H bondsTaking DDQ-mediated activation of benzylic and allylic sp3 C-H bonds and restulted CDC reaction as the strategy, we designed and synthesized a series of 1,2-diarylprop-l-ene derivatives as substrates. Instead of obtaining 2-arylindene as the product via intramolecular CDC reaction, sbustituted cyclopentene derivatives were obtained via intermolecular self-coupling of the substrates when no nucleophilic reagent was added. Inspired by this, we used styrenes as nucleophilic reagents and fortunatly obtained a series of polysbstituted naphthalene derivatives through DDQ mediated tandem CDC reaction with subsequent Friedel-Crafts type reaction and aromatization catalyzed by FeCl3. The success of this reaction largely expends the scope of the substrates for CDC reaction and constructs polysubstituted naphthalenes, which are considered to be of much use, in high efficiency due to its high regioselectivity and mutistep in one-pot. What's more, all of the advantages, summarized as simple substrate, cheap and stable catalyst, mild condition and tolerance of air and moisture, make this reaction to be complementary to previous reported synthetic method for polysubstituted naphthalenes, and even to be of more superiority and potential value for application.