Metal-free Oxidative C-H Functionalization And Decarboxylation

Transition-metal-catalyzed C(sp3)-H activation and decarboxylative couplings have emerged as important synthetic methods for C-C or C-N bond formation because they are straightforward and have economic advantages over present procedures by employing prefunctionalized substrates. However, these reactions are restricted because of the toxicity of catalysts and their use of expensive transition metals as catalysts. To approach the potential application of these methods, strategies with lower cost, less waste and milder conditions are highly desirable. Metal-free catalysis may be an attractive advance as a valuable alternative to transition metal catalysis in C(sp3)-H activation and decarboxylative couplingsOur research about "Metal-free Oxidative C-H Functionalization and Decarboxylation" mainly includes four sections.Section1:A catalyst-free benzylic C-H bond addition of azaarenes to imines.A highly efficient synthesis of trans-alkenylazaarene under catalyst-free conditions was developed via the addition of methylazaarenes to N-sulfonyl aldimines and a subsequent C-N elimination in situ. A one-pot procedure for this addition-elimination was also developed without presynthesis of imines substrate.Section2:Metal-free intramolecular oxidative decarboxylative amination for the synthesis of quinazolines.We have developed a metal-free intramolecular oxidative decarboxylative coupling of a-amino acids under mild conditions. This reaction is applicable to the synthesis of quinazolines that tolerate aryl and alkyl substituents. Compared to traditional decarboxylative couplings, this coupling displays many advantages, such as being metal-free, water and air-tolerant, low toxicity and environmentally benign.Section3:Selective iodine-catalyzed intermolecular oxidative amination of C(sp3)-H Bonds with ortho-carbonyl-substituted anilines to give quinazolinesWe have developed an iodine-catalyzed oxidative amination of C(sp3)-H bonds adjacent to nitrogen or oxygen atoms for the synthesis of quinazolines from orthocarbonyl-substituted anilines, ammonia, and solvents, such as N-alkylamides, ethers, and alcohols. Compared with previous reports, this novel protocol is distinguished by1) the lack of expensive transition metals;2) operational simplicity;3) the fact that an inert atmosphere or dry solvents are not required;4) a wide tolerance of various functional groups; and5) the production of alcohol and water as the only waste. Moreover, a13C-labeling experiment unambiguously established that the additional carbon atom of quinazolines was derived from the N-methyl group of N-methylamide, rather than the acyl group. More importantly, the selectivity of the reactions of primary and secondary C-H bonds was the first observed in oxidative C(sp3)-H aminations.Section4:Mild metal-free sequential dual oxidative amination of C(sp3)-H bonds: efficient synthesis of imidazo[1,5-a]pyridinesWe have developed a metal-free sequential dual oxidative amination of C(sp3)-H bonds for the synthesis of imidazo[1,5-a]pyridines under mild conditions. The reaction was involved in two oxidative C-N couplings and one oxidative dehydrogenation process with six hydrogen atoms removed. Notably, this novel protocol is distinguished by1) the lack of any expensive transition metals;2) operational simplicity;3) room temperature;4) the fact that an inert atmosphere or dry solvents are not required;5) a broad substrate scope; and6) the production of alcohol and water as the only waste.