RESUMEN
Directed C-H functionalization has been realized as a complimentary technique to achieve borylation at a distal position of aliphatic amines. Here, we demonstrated the oxidative borylation at the distal δ-position of aliphatic amines using various borylating agents, a palladium catalyst, and a rightly tuned ligand in the presence of a cheap oxidant. Moreover, an organopalladium δ-C(sp3 )-H-activated intermediate has been isolated and crystallographically characterized to get mechanistic insight.
RESUMEN
Biaryl compounds are extremely important structural motifs in natural products, biologically active components and pharmaceuticals. Selective synthesis of biaryls by distinguishing the subtle reactivity difference of distal arene C-H bonds are significantly challenging. Herein, we describe para-selective C-H arylation, which is acheived by a unique combination of a meta-directing group and norbornene as a transient mediator. Upon direct meta-C-H palladation, one-bond relay palladation occurs in presence of norbornene and subsequently para-C-H arylation is achieved for sulfonates, phosphonates and phenols bearing 2,6-disubstitution patterns. The protocol is amenable to electron-deficient aryl iodides. Multisubstituted arenes and phenols are obtained by postsynthetic modification of the products. The protocol allows the synthesis of hexa-substituted benzene by sequential selective distal C-H functionalization.
RESUMEN
Transition metal catalysis plays a pivotal role in transforming unreactive C-H bonds. However, regioselective activation of distal aliphatic C-H bonds poses a tremendous challenge, particularly in the absence of directing templates. Activation of a methylene C-H bond in the presence of methyl C-H is underexplored. Here we show activation of a methylene C-H bond in the presence of methyl C-H bonds to form unsaturated bicyclic lactones. The protocol allows the reversal of the general selectivity in aliphatic C-H bond activation. Computational studies suggest that reversible C-H activation is followed by ß-hydride elimination to generate the Pd-coordinated cycloalkene that undergoes stereoselective C-O cyclization, and subsequent ß-hydride elimination to provide bicyclic unsaturated lactones. The broad generality of this reaction has been highlighted via dehydrogenative lactonization of mid to macro ring containing acids along with the C-H olefination reaction with olefin and allyl alcohol. The method substantially simplifies the synthesis of important bicyclic lactones that are important features of natural products as well as pharmacoactive molecules.