An Iridium/Aluminum Cooperative Strategy for the ß-C(sp3 )-H Borylation of Saturated Cyclic Amines.

Despite the widespread success in the functionalization of C(sp2 )-H bonds, the deliberate functionalization of C(sp3 )-H bonds in a highly site- and stereoselective manner remains a longstanding challenge. Herein, we report an iridium/aluminum cooperative catalytic system that enables the ß-selective C-H borylation of saturated cyclic amines and lactams. Furthermore, we have accomplished an enantioselective variant using binaphthol-derived chiral aluminum catalysts to forge C-B bonds with high levels of stereocontrol. Computational studies suggest that the formation of a Lewis pair with the substrates is crucial to lower the energy of the transition state for the rate-determining reductive elimination step.

The Kumada-Tamao-Corriu Coupling Reaction Catalyzed by Rhodium-Aluminum Bimetallic Complexes.

Rhodium-aluminum bimetallic complexes catalyze the Kumada-Tamao-Corriu (KTC) cross-coupling reaction using arylmagnesium compounds that are generated from the corresponding aryl fluorides or chlorides in situ by these catalysts. This method allows the challenging KTC coupling reaction to be carried out using aryl fluorides as nucleophiles, which affords various biaryls.

C2-Selective silylation of pyridines by a rhodium-aluminum complex.

We have developed a C2-selective mono-silylation of a variety of pyridines using a Rh-Al complex. Both the site- and mono-selectivity are controlled via the pyridine coordination to the Lewis-acidic Al center prior to the activation of the pyridine C(2)-H bond at the proximal Rh center. A reaction mechanism is proposed based on several mechanistic studies, including the isolation of a (2-pyridyl)silylrhodium intermediate.

Selective C-O Bond Reduction and Borylation of Aryl Ethers Catalyzed by a Rhodium-Aluminum Heterobimetallic Complex.

We report the catalytic reduction of a C-O bond and the borylation by a rhodium complex bearing an X-type PAlP pincer ligand. We have revealed the reaction mechanism based on the characterization of the reaction intermediate and deuterium-labeling experiments. Notably, this novel catalytic system shows steric-hindrance-dependent chemoselectivity that is distinct from conventional Ni-based catalysts and suggests a new strategy for selective C-O bond activation by heterobimetallic catalysis.

Magnesiation of Aryl Fluorides Catalyzed by a Rhodium-Aluminum Complex.

We report the magnesiation of aryl fluorides catalyzed by an Al-Rh heterobimetallic complex. We show that the complex is highly reactive to cleave the C-F bonds across the polarized Al-Rh bond under mild conditions. The reaction allows the use of an easy-to-handle magnesium powder to generate a range of arylmagnesium reagents from aryl fluorides, which are conventionally inert to such metalation compared with other aryl halides.

Nickel-catalysed anti-Markovnikov hydroarylation of unactivated alkenes with unactivated arenes facilitated by non-covalent interactions.

Anti-Markovnikov additions to alkenes have been a longstanding goal of catalysis, and anti-Markovnikov addition of arenes to alkenes would produce alkylarenes that are distinct from those formed by acid-catalysed processes. Existing hydroarylations are either directed or occur with low reactivity and low regioselectivity for the n-alkylarene. Herein, we report the first undirected hydroarylation of unactivated alkenes with unactivated arenes that occurs with high regioselectivity for the anti-Markovnikov product. The reaction occurs with a nickel catalyst ligated by a highly sterically hindered N-heterocyclic carbene. Catalytically relevant arene- and alkene-bound nickel complexes have been characterized, and the rate-limiting step was shown to be reductive elimination to form the C-C bond. Density functional theory calculations, combined with second-generation absolutely localized molecular orbital energy decomposition analysis, suggest that the difference in activity between catalysts containing large and small carbenes results more from stabilizing intramolecular non-covalent interactions in the secondary coordination sphere than from steric hindrance.

Site-Selective Linear Alkylation of Anilides by Cooperative Nickel/Aluminum Catalysis.

We report meta- and para-selective linear alkylation reactions of anilides with alkenes by nickel/N-heterocyclic carbene (NHC) and aluminum catalysis. With a less bulky NHC, the alkylation reaction of N-methyl-N-phenylcyclohexanecarboxamides proceeded mainly at the meta position. In contrast, a bulky NHC ligand led to the para-selective alkylation of N-sec-alkyl anilides.

C3-Selective alkenylation of N-acylindoles with unactivated internal alkynes by cooperative nickel/aluminium catalysis.

Highly regio- and stereoselective alkenylation of N-acylindoles with unactivated internal alkynes has been accomplished by cooperative nickel/aluminium catalysis to afford C3-alkenylated indoles. Coordination of the acyl moiety to a bulky aluminium-based Lewis acid plays a crucial role in the selective functionalization at the C3-position by electron-rich nickel(0) catalysis.

para-Selective C-H Borylation of (Hetero)Arenes by Cooperative Iridium/Aluminum Catalysis.

para-Selective C-H borylation of benzamides and pyridines has been achieved by cooperative iridium/aluminum catalysis. A combination of iridium catalysts commonly employed for arene C-H borylation and bulky aluminum-based Lewis acid catalysts provides an unprecedented strategy for controlling the regioselectivity of C-H borylation to give variously substituted (hetero)arylboronates, which are versatile synthetic intermediates for complex multi-substituted aromatic compounds.

para-Selective Alkylation of Sulfonylarenes by Cooperative Nickel/Aluminum Catalysis.

A method for the para-selective alkylation of a variety of arenesulfonamides and aromatic sulfones with 1-alkenes by cooperative nickel/aluminum catalysis has been developed. Taking advantage of the sulfornyl functionality serving as a removable ortho-directing group, the reaction can be applied to facile access to 1,3-dialkyl-substitued benzenes.

Theoretical Study of Nickel-Catalyzed Selective Alkenylation of Pyridine: Reaction Mechanism and Crucial Roles of Lewis Acid and Ligands in Determining the Selectivity.

Selective alkenylation of pyridine is challenging in synthetic organic chemistry due to the poor reactivity and regioselectivity of the aromatic ring. We theoretically investigated Ni-catalyzed selective alkenylation of pyridine with DFT. The first step is coordination of the pyridine-AlMe3 adduct with the active species Ni(0)(NHC)(C2H2) 1 in an η2-fashion to form an intermediate Int1. After the isomerization of Int1, the oxidative addition of the C-H bond of pyridine across the nickel-acetylene moiety occurs via a transition state TS2 to form a Ni(II)(NHC) pyridyl vinyl intermediate Int3. This oxidative addition is rate-determining. The next step is C-C bond formation between pyridyl and vinyl groups leading to the formation of vinyl-pyridine (P1). One of the points at issue in this type of functionalization is how to control the regioselectivity. With the use of Ni(NHC)/AlMe3 catalyst, the C4- and C3-alkenylated products (ΔG°â§§ = 17.4 and 21.5 kcal mol-1, respectively) are formed preferably to the C2 one (ΔG°â§§ = 22.0 kcal mol-1). The higher selectivity of the C4-alkenylation over the C3 and the C2 ones is attributed to the small steric repulsion between NHC and AlMe3 in the C4-alkenylation. Interestingly, with Ni(P(i-Pr)3)/AlMe3 catalyst, the C2-alkenylation occurs more easily than the C3 and C4 ones. This regioselectivity arises from the smaller steric repulsion induced by P(i-Pr)3 than by bulky NHC. It is notable that AlMe3 accelerates the alkenylation by inducing the strong CT from Ni to pyridine-AlMe3. In the absence of AlMe3, pyridine strongly coordinates with the Ni atom through the N atom, which increases Gibbs activation energy (ΔG°â§§ = ∼27 kcal mol-1) of the C-H bond activation. In other words, AlMe3 plays two important roles, acceleration of the reaction and enhancement of the regioselectivity for the C4-alkenylation.

para-Selective Alkylation of Benzamides and Aromatic Ketones by Cooperative Nickel/Aluminum Catalysis.

We report a method that ensures the selective alkylation of benzamides and aromatic ketones at the para-position via cooperative nickel/aluminum catalysis. Using a bulky catalyst/cocatalyst system allows reactions between benzamides and alkenes to afford the corresponding para-alkylated products. The origin of the high para-selectivity has also been investigated by density functional theory calculations.

Arylboration of 1-Arylalkenes by Cooperative Nickel/Copper Catalysis.

A method for the arylboration of 1-arylalkenes with bis(pinacolato)diboron and aryl chlorides or tosylates by cooperative Ni/Cu catalysis has been developed, which affords 2-boryl-1,1-diarylalkanes in high regio- and stereoselectivity. Under the applied conditions, this method is tolerant toward various functional groups, including silyl ether, alkoxycarbonyl, and aminocarbonyl moieties.

Anti-Markovnikov hydroheteroarylation of unactivated alkenes with indoles, pyrroles, benzofurans, and furans catalyzed by a nickel-N-heterocyclic carbene system.

We report the catalytic addition of C-H bonds at the C2 position of heteroarenes, including pyrroles, indoles, benzofurans, and furans, to unactivated terminal and internal alkenes. The reaction is catalyzed by a combination of Ni(COD)2 and a sterically hindered, electron-rich N-heterocyclic carbene ligand or its analogous Ni(NHC)(arene) complex. The reaction is highly selective for anti-Markovnikov addition to α-olefins, as well as for the formation of linear alkylheteroarenes from internal alkenes. The reaction occurs with substrates containing ketones, esters, amides, boronate esters, silyl ethers, sulfonamides, acetals, and free amines.

Hydroarylation of alkynes catalyzed by nickel.

Nickel catalysts derived from bis(1,5-cyclooctadiene)nickel [Ni(cod)(2)] and trialkylphosphines effect hydroarylation of alkynes through functionalization of C-H bonds of arenes including benzo-fused five-membered heteroarenes, pyridine-N-oxides, pyridines, 2-pyridones, and perfluoroarenes. The reactions proceed with excellent stereo- and regioselectivity to give disubstituted arylethenes in good yields. Use of Lewis acid (LA) co-catalysts is crucial for success in reactions of imidazoles, pyridines, and 2-pyridones; it is possible that coordination of the LA to the nitrogen or oxygen functionalities of such substrates increases the reactivity of their C-H bonds towards nickel(0) species.

Nickel-catalysed cross-coupling reaction of aryl(trialkyl)silanes with aryl chlorides and tosylates.

Using highly stable, readily accessible, and recyclable 2-(2-hydroxyprop-2-yl)cyclohexyl-substituted arylsilanes activated by a mild carbonate base, nickel-catalysed silicon-based aryl-aryl cross-coupling reaction proceeds for the first time with inexpensive aryl chlorides and tosylates in a highly chemoselective manner.

Selective C-4 alkylation of pyridine by nickel/Lewis acid catalysis.

Direct C-4-selective addition of pyridine across alkenes and alkynes is achieved for the first time by nickel/Lewis acid cooperative catalysis with an N-heterocyclic carbene ligand. A variety of substituents on both alkenes and pyridine are tolerated to give linear 4-alkylpyridines in modest to good yields. The addition across styrene, on the other hand, gives branched 4-alkylpyridines. A single example of C-4-selective alkenylation is also described.

Nickel/Lewis acid-catalyzed cyanoesterification and cyanocarbamoylation of alkynes.

Cyanoformates and cyanoformamides are found to add across alkynes by nickel/Lewis acid (LA) cooperative catalysis to give beta-cyano-substituted acrylates and acrylamides, respectively, in highly stereoselective and regioselective manners. The resulting adducts serve as versatile synthetic building blocks through chemoselective transformations of the ester, amide, and cyano groups as demonstrated by the synthesis of typical structures of beta-cyano ester, beta-amino nitrile, gamma-lactam, disubstituted maleic anhydride, and gamma-aminobutyric acid. The related reactions of cyanoformate thioester and benzoyl cyanide, on the other hand, are found to add across alkynes with decarbonylation in the presence of a palladium/LA catalyst.