Hydroboration of alkenes is a classical reaction in organic synthesis, in which alkenes react with boranes to give alkylboranes, with subsequent oxidation resulting in alcohols. The double bond (π-bond) of alkenes can be readily reacted with boranes owing to its high reactivity. However, the single bond (σ-bond) of alkanes has never been reacted. To pursue the development of σ-bond cleavage, we selected cyclopropanes as model substrates since they present a relatively weak σ-bond. Herein, we describe an iridium-catalyzed hydroboration of cyclopropanes, resulting in β-methyl alkylboronates. These unusually branched boronates can be derivatized by oxidation or cross-coupling chemistry, accessing "designer" products that are desired by practitioners of natural product synthesis and medicinal chemistry. Furthermore, mechanistic investigations and theoretical studies revealed the enabling role of the catalyst. Recently, several chemists including our group reported an iridium-catalyzed C-H borylation of cyclopropanes [19-21]. In one report, cyclopropanes were reacted with iridium complexes with a nitrogen bidentate ligand, 3,4,7,8-tetramethylphenanthroline (3,4,7,8-tetraMephen), which engendered a cyclopropane carbonhydrogen activation to afford borylated cyclopropanes (Fig. 1B). With the aim of achieving cyclopropane carbon-carbon activation, we forged a blueprint for selective bond activation. If an appropriate ligand were used, it might be possible to perform a "chemoselectivity switch" from C-H (intermediate A) to CC (intermediate B) bond activation in which the selectivity of CC activation could be achieved by reaction of the catalyst with the sterically less hindered Cb-Cg bond [22-24]. With these goals in mind, we conducted an extensive screening of ligands, and by using 2-[4-(1,1-dimethylethyl)-4,5-dihydro-2-oxazolyl]quinoline (t-Bu-Quinox), we achieved the first iridium-catalyzed σ-bond hydroboration of cyclopropanes (Fig. 1C). We initiated our study by finding a suitable ligand for the target reaction, consisting of N-cyclopropylpivalamide (1a) as a model mono-substituted cyclopropane. 1a was reacted with pinacolborane (H-Bpin: 1.5 equiv) in the presence of Ir dimer [Ir(OMe)(cod)]2 (5 mol%) and ligands (5 mol%) in THF at 80 ºC under nitrogen atmosphere. After an extensive screening of ligands (see Supplementary Materials), it was found that t-BuQuinox (L1) effects the cleavage of the σ-bond and forms hydroboration product 2a in 62% yield
A decarbonylative C-H coupling of azoles and aromatic esters by palladium catalysis is described. Our previously reported Ni-catalyzed C-H coupling of azoles and aromatic esters has a significant drawback regarding the substrate scope. Herein, we employ palladium catalysis instead of nickel, resulting in a broader substrate scope in terms of azoles and aromatic esters.
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