The ligand-enabled development of ortho and meta C–H borylation of aromatic aldehydes is reported. It was envisaged that while ortho borylation could be achieved using tert-butylamine as the ...traceless protecting/directing group, meta borylation proceeds via an electrostatic interaction and a secondary interaction between the ligand of the catalyst and the substrate. These ligand–substrate electrostatic interactions and secondary B–N interactions provide an unprecedented controlling factor for meta-selective C–H activation/borylation.
Here we describe the discovery of a new class of C–H borylation catalysts and their use for regioselective C–H borylation of aromatic, heteroaromatic, and aliphatic systems. The new catalysts have ...Ir–C(thienyl) or Ir–C(furyl) anionic ligands instead of the diamine-type neutral chelating ligands used in the standard C–H borylation conditions. It is reported that the employment of these newly discovered catalysts show excellent reactivity and ortho-selectivity for diverse classes of aromatic substrates with high isolated yields. Moreover, the catalysts proved to be efficient for a wide number of aliphatic substrates for selective C(sp3)–H bond borylations. Heterocyclic molecules are selectively borylated using the inherently elevated reactivity of the C–H bonds. A number of late-stage C–H functionalization have been described using the same catalysts. Furthermore, we show that one of the catalysts could be used even in open air for the C(sp2)–H and C(sp3)–H borylations enabling the method more general. Preliminary mechanistic studies suggest that the active catalytic intermediate is the Ir(bis)boryl complex, and the attached ligand acts as bidentate ligand. Collectively, this study underlines the discovery of new class of C–H borylation catalysts that should find wide application in the context of C–H functionalization chemistry.
A new catalytic method for the denitrogenative transannulation/cyclopropanation of in‐situ‐generated 2‐(diazomethyl)pyridines is described using a cobalt‐catalyzed radical‐activation mechanism. The ...method takes advantage of the inherent properties of a CoIII‐carbene radical intermediate and is the first report of denitrogenative transannulation/cyclopropanation by a radical‐activation mechanism, which is supported by various control experiments. The synthetic benefits of the metalloradical approach are showcased with a short total synthesis of (±)‐monomorine.
Denitrogenative transannulation/cyclopropanation of in‐situ‐generated 2‐(diazomethyl)pyridine is presented, which involves a cobalt‐catalyzed radical‐activation mechanism. A cobalt(II)‐metalloradical undergoes radical addition to alkynes during denitrogenative transannulation, or to alkenes during cyclopropanation, forming indolizines and cyclopropanes, respectively
A concept for intramolecular denitrogenative C(sp3)–H amination of 1,2,3,4-tetrazoles bearing unactivated primary, secondary, and tertiary C–H bonds is discovered. This catalytic amination follows ...an unprecedented metalloradical activation mechanism. The utility of the method is showcased with the short synthesis of a bioactive molecule. Moreover, an initial effort has been embarked on for the enantioselective C(sp3)–H amination through the catalyst design. Collectively, this study underlines the development of C(sp3)–H bond functionalization chemistry that should find wide application in the context of drug discovery and natural product synthesis.
An efficient strategy for the para-selective borylation of aromatic esters is described. For achieving high para-selectivity, a new catalytic system has been developed modifying the core structure of ...the bipyridine. It has been proposed that the L-shaped ligand is essential to recognize the functionality of the oxygen atom of the ester carbonyl group via noncovalent interaction, which provides an unprecedented controlling factor for para-selective C–H activation/borylation.
A silanol-directed, Pd(II)-catalyzed C–H alkenylation of phenols is reported. This work features silanol, as a novel traceless directing group, and a directed o-C–H alkenylation of phenols. This new ...method allows for efficient synthesis of diverse alkenylated phenols, including an estrone derivative.
An efficient strategy for the intramolecular denitrogenative transannulation/C(sp2)–H amination of 1,2,3,4-tetrazoles bearing C8-substituted arenes, heteroarenes, and alkenes is described. The ...process involves the generation of the metal–nitrene intermediate from tetrazole by the combination of Cp*IrCl22 and AgSbF6. It has been shown that the reaction proceeds via an unprecedented electrocyclization process. The method has been successfully applied for the synthesis of a diverse array of α-carbolines and 7-azaindoles.
A unique concept for the intermolecular denitrogenative annulation of 1,2,3,4‐tetrazoles and alkynes was discovered by using a catalytic amount of Fe(TPP)Cl and Zn dust. The reaction precludes the ...traditional, more favored click reaction between an organic azide and alkynes, and instead proceeds by an unprecedented metalloradical activation. The method is anticipated to advance access to the construction of important basic nitrogen heterocycles, which will in turn enable discoveries of new drug candidates.
1,2,3,4: A unique intermolecular denitrogenative annulation of 1,2,3,4‐tetrazoles and alkynes was discovered by employing a catalytic amount of Fe(TPP)Cl and Zn dust. This reaction precludes the traditional click reaction between organic azides and alkynes.
A general catalytic method using a Mn‐porphyrin‐based catalytic system is reported that enables two different reactions (click reaction and denitrogenative annulation) and affords two different ...classes of nitrogen heterocycles, 1,5‐disubstituted 1,2,3‐triazoles (with a pyridyl motif) and 1,2,4‐triazolo‐pyridines. Mechanistic investigations suggest that although the click reaction likely proceeds through an ionic mechanism, which is different from the traditional click reaction, the denitrogenative annulation reaction likely proceeds via an electrophilic metallonitrene intermediate rather than a metalloradical intermediate. Collectively, this method is highly efficient and offers several advantages over other methods. For example, this method excludes a multi‐step synthesis of the N‐heterocyclic molecules described and produces only environmentally benign N2 gas a by‐product.
A Mn‐porphyrin‐based catalytic method that enables access to two different classes of nitrogen heterocycles is reported. Mechanistic investigations found that a 1,3‐cycloaddition click reaction occurs directly via the Mn‐bound complex, whereas denitrogenative annulation proceeds through an Mn‐N complex. The reported method is compatible with a wide range of substrates for both reactions.
A silanol-directed, Pd-catalyzed C–H oxygenation of phenols into catechols is presented. This method is highly site selective and general, as it allows for oxygenation of not only electron-neutral ...but also electron-poor phenols. This method operates via a silanol-directed acetoxylation, followed by a subsequent acid-catalyzed cyclization reaction into a cyclic silicon-protected catechol. A routine desilylation of the silacyle with TBAF uncovers the catechol product.
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