ABSTRACT
The divergent synthesis of two indane polyketides of the indidene family, namely (±)-indidene A (11 steps, 1.7 %) and (+)-indidene C (13 steps, 1.3 %), is reported. The synthesis of the trans-configured common indane intermediate was enabled by palladium(0)-catalyzed methylene C(sp3 )-H arylation, which was performed in both racemic and enantioselective (e.r. 99 : 1) modes. Further elaboration of this common intermediate by nickel-catalyzed dehydrogenative coupling allowed the rapid installation of the aroyl moiety of (±)-indidene A. In parallel, the biphenyl system of (±)- and (+)-indidene C was constructed by Suzuki-Miyaura coupling. These investigations led us to revise the structures of indidenes B and C.
ABSTRACT
A ligand-controlled site-selective C(sp3 )-H arylation of heteroaromatic ketones has been developed using Pd catalysis. The reaction occurred selectively at the α- or ß-position of the ketone side-chain. The switch from α- to ß-arylation was realized by addition of a pyridone ligand. The α-arylation process showed broad scope and high site- and chemoselectivity, whereas the ß-arylation was more limited. Mechanistic investigations suggested that α-arylation occurs through C-H activation/oxidative addition/reductive elimination whereas ß-arylation involves desaturation and aryl insertion.
Subject(s)
Ketones , Palladium , Catalysis , Ligands , Oxidation-ReductionABSTRACT
In the past few decades, processes that involve transition-metal catalysis have represented a major part of the synthetic chemist's toolbox. Recently, the interest has shifted from the well-established cross-coupling reactions to C-H bond functionalization, thus making it a current frontier of transition-metal-catalyzed reactions. Constant progress in this field has led to the discovery of enantioselective methods to generate and control various types of stereogenic elements, thereby demonstrating its high value to generate scalemic chiral molecules. The present review is dedicated to enantioselective Pd0 -catalyzed C-H activation, which may be considered as an evolution of Pd0 -catalyzed cross-couplings, with a focus on the different chiral ligands and catalysts that enable these transformations.
