Transition-Metal-Catalyzed C-C, C-S And C-O Bond Forming Reactions And Their Applications

Transition-metal-catalyzed C-C, C-S and C-0bond forming reactions have found wide application in natural product and pharmaceutical synthesis in which these reactions are popular but challenging.In this study, we mainly investigated the transition-metal-catalyzed C-C and C-S cross-coupling reactions and their applications in natural product synthesis. The contents are as below:1. Cobalt-catalyzed asymmetric Kumada cross-coupling reaction (C-C bond formation)The first cobalt-catalyzed highly enantioselective Kumada cross-coupling of a-bromo esters with Aryl Grignard reagent was realized. A variety of chiral a-arylalkanoic esters were prepared in excellent enantioselectivity (up to97%ee). This method was successfully conducted on gram-scale and applied to the synthesis of highly enantioenriched (S)-fenoprofen and (S)-arturmerone.2. Palladium-catalyzed asymmetric allylic alkylation of toluene derivatives (C-C bond formation)We have successfully developed the first palladium-catalyzed AAA reaction employing toluene-derived pronucleophiles. This method provides ready access to the enantioenriched "a-2-propenyl benzyl" motifs. A tandem allylation/demetalation procedure was also introduced for a one-pot synthesis of chromium free allylated products. This approach was employed to prepare a nonsteroidal anti-inflammatory drug analogue.3. Palladium-catalyzed debenzylative cross-coupling reaction of aryl benzyl sulfide (C-S bond formation)We developed a novel debenzylative approach to synthesize diaryl sulfides. We also investigated the reaction mechanism which indicated that the catalyst derived from Pd(dba)2and Nixantphos can catalyze a-arylation of sulfides, C-S bond cleavage and C-S bond formation in a tricatalytic cycle.4. Palladium-catalyzed tantem arylation/oxidation of diarylmethanes (C-C and C-0bond formation)We have developed a one-pot tandem arylation/oxidation of diarylmethane derivatives for the convenient synthesis of triarylmethanols under mild reaction conditions. The contents fall primarily into two categories:(1) arylation/oxidation of benzyl pyridines;(2) arylation/oxidation of fluorene.5. Asymmetric total synthesis of Panaxytriol and their stereoisomersWe have conducted the asymmetric total synthesis of Panaxytriol and their stereosiomers. In addition,(3R,9R,105)-,(3R,9S,10R)-,(35,9R,105)-,(3S,95,10R)-panaxytriol were prepared for the first time.