Pd(?)-Catalyzed C(sp~3)-H Activation Reactions

The transition metal-catalyzed direct functionalization of inert C-H bonds represents one of the most efficient methods for the conversion of simple molecules into complex compounds,and thus has been an important area in organic synthesis.The C(sp3)-H bond activation is a formidable challenge due to the high bond energy,low acidity,and poor reaction intermediate stability.In addition,C(sp3)-H bonds are widely present in organic compounds,so there is another concern about the selectivity in the activation of such bonds.The Pd(II)-catalyzed C(sp3)-H bond functionalization is an efficient method to achieve its selective conversion.There are mainly two strategies to realize the regioselectivity:one is the introduction of a directing group,and the other is the selective activation through the bond energy difference.The latter method will be used here to achieve the selective conversion of multiple C(sp3)-H bonds.Firstly,we established a Pd(II)/amine cooperative catalysis to enable the enantioselective functionalization of inactive C-H bonds y to the formyl group in aliphatic aldehydes.Aliphatic aldehydes were directly used in[4 + 2]cyclization with quinone derivatives to construct bicyclic compounds with chiral quaternary carbon center.The reaction has the advantages of pot-,step-,and atom economy,and uses oxygen as the terminal oxidant.More importantly,the concept presented herein indicates a new and robust pathway to functionalize inactive C-H bonds in aliphatic carbonyls.By employing the deacylative nucleophile generation,we accomplished an ?-allylation of nitroalkanes,ketones,and esters,to generate products with tertiary or quaternary carbon center.In addition,the reaction can also be carried out in a one-pot,two-step process to build up products with a 1,6-diene subunit from simple substrate.Moreover,this system can also be expanded to the synthesis of 1,4-enynes.Finally,we successfully established a dehydrogenative coupling reaction between 1,4-dienes and a-substituted aldehydes by cooperative catalysis of palladium,chiral phosphoric acid,and amine.A wide range of a-allylated aldehydes could be generated in high yields,and high levels of enantio-,regio-and E/Z-selectivity.More importantly,we also found that achiral phosphine ligands exert important influence on the catalytic acitivity and selectivity of the palladium complexes.