Cobalt-catalyzed three-component assembly of aromatic oximes with substituted dienes and formaldehyde.

A cobalt-catalyzed three-component assembly of substituted aryl oximes with dienes and formaldehyde via C-H bond activation is described. This protocol affords highly regio- and chemoselective substituted homoallylic alcohols with moderate-to-excellent yields. The scope of this protocol has been extensively explored with various substituted aryl ketoximes and aldoximes. Butadiene and internally substituted dienes are also well compatible for this transformation. A plausible reaction mechanism is proposed to account for the present reaction and is supported by deuterium labeling studies.

Ir(III)-Catalyzed Tandem Annulation of Aromatic Amides with 1,6-Diynes via Dual C-H Bond Activation.

An Ir(III)-catalyzed annulation of aryl amides with 1,6-diynes via ortho- as well as meta-dual C-H bond activation reaction is reported. The scope of the annulation reaction was examined with various substituted aryl amides, as well as 1,6-diynes. In this protocol, 1,6-diynes exhibit diverse reactivity compared with internal alkynes. It is important to note that the three C-C bond formation takes place consecutively via ortho followed by meta-dual C-H bond annulation by using a weak chelating group in one pot. A possible catalytic reaction mechanism was proposed to account for the annulation reaction.

Synthesis of Aryl Naphthoquinones and Maleimides via Pd(II)-Catalyzed Template-Assisted m-C(sp2)-H Functionalization Reaction.

An efficient approach for the synthesis of substituted aryl naphthoquinones via a Pd(II)-catalyzed template-assisted m-C(sp2)-H bond functionalization reaction of arylmethane sulfonates have been demonstrated. The method involves usage of less expensive and abundant pharmacologically important scaffold naphthoquinone. A wide range of arylmethane sulfonates were examined and found to be compatible with the protocol. The protocol has also been further extended to the synthesis of various substituted aryl maleimide scaffolds. A plausible reaction mechanism has also been proposed to account for the selective distal m-C(sp2)-H bond functionalization reaction.

Palladium-Catalyzed Selective Benzylic C-H Alkylation of Aromatic Sulfonamides with Maleimides.

An efficient method for the selective benzylic C-H alkylation of sulfonamides using maleimides has been developed. The reaction proceeds via the benzylic C(sp3)-H bond activation of sulfonamide in the presence of a Pd(II) catalyst without requiring any oxidant, additive, or external ligand. This methodology is highly compatible with a wide variety of substituted maleimides. A plausible reaction mechanism is also proposed to account for this alkylation reaction.

Co(III)-catalyzed regioselective benzannulation of substituted pyridones with 1,6-diynes via dual C-H bond activation.

A Co(III)-catalyzed site-selective C5 and C6 benzannulation of substituted pyridones with 1,6-diynes via dual C-H bond activation has been reported. The scope of the benzannulation reaction was examined with various substituted 2-pyridyl pyridones and 1,6-diynes. The combination of cuprous acetate and silver carbonate plays a crucial role in the success of the reaction. A plausible reaction mechanism was proposed and supported by deuterium labelling studies and radical trapping experiments.

Palladium-Catalyzed Ligand-Enabled Cyclization of Substituted Aliphatic Carboxylic Acids with Allylic Electrophiles.

A palladium-catalyzed cyclization of the ß-C(sp3)-H bond of aliphatic carboxylic acids with allylic electrophiles providing five-membered γ-lactones in good to excellent yields is demonstrated. An acetyl-protected aminoethyl phenyl thioether ligand is used to promote the C-H activation reaction. A diverse range of allylic electrophiles such as allyl alcohols, allyl acetates, allyl sulfones, allyl phosphonate, allyl amine, and allyl ester have been utilized for this reaction. A feasible reaction mechanism has been proposed to account for the present cyclization reaction.

Palladium-catalyzed site-selective functionalization of unactivated alkenes with vinylcyclopropanes aided by weakly coordinating native amides.

Herein, we have demonstrated a palladium-catalyzed regioselective allylation of unactivated alkenes with vinylcyclopropanes assisted by weak-coordinating native amides. The reaction exhibits wide substrate scope and excellent ß-selectivity. Substrate diversification was performed to demonstrate the synthetic utility of the reaction. Mechanistic investigations were carried out to provide an insight into the reaction mechanism.

Synthesis of 1H-Isoindoles via Ruthenium(II)-Catalyzed Cyclization of Benzimidates with Alkenes.

A Ru(II)-catalyzed efficient synthesis of 1H-isoindoles via the cyclization of benzimidates with alkenes has been demonstrated. This methodology exhibits high compatibility with various functionalized activated and unactivated olefins containing different sensitive functional groups. This protocol provides an effective method for synthesizing various 1H-isoindole derivatives in decent to excellent yields. Notably, the ortho-alkenylation of benzimidates with unactivated alkenes was achieved. A potential reaction mechanism has been suggested that involves C-H activation, 1,2 insertion, and ß-hydride elimination subsequent to aza-Michael addition.

Pd(II)-catalyzed cyclization of 2-methyl aromatic ketones with maleimides through weak chelation assisted dual C-H activation.

A palladium-catalyzed dual C-H functionalization of substituted aromatic ketones and ester with maleimides leading to tricyclic heterocyclic molecules with good to excellent yield is reported. In this protocol, weak chelation of the carbonyl groups has been successfully utilized for the selective activation of the ortho-methyl C(sp3)-H bond instead of the ortho-C(sp2)-H bond in the presence of an external bidentate ligand Ac-Ile-OH. The reaction proceeds through two-fold C-H activation to generate a five-membered cyclic ring. The first C-H activation takes place selectively at the benzylic position followed by a second C-H bond activation at the meta position. The protocol demonstrates compatibility among diverse substituted aromatic ketones and ester as well as various substituted maleimides. Further derivatization of the tricyclic ketone to an alcohol exhibits the synthetic applicability of the protocol. Also, a plausible reaction mechanism has been proposed.

Nickel-Catalyzed Tandem Cyclization of 1,6-Diynes with Indolines/Indoles through Dual C-H Bond Activation.

A nickel-catalyzed site-selective tandem cyclization of 1,6-diynes with substituted indolines or indoles through consecutive dual C-H bond activation is described. In the reaction, substituted fused indole and carbazole derivatives were observed in good to excellent yields, in which three consecutive C-C bonds formed in one pot. Later, in the presence of DDQ, the aromatization of the indoline derivative was converted to the indole derivative. A possible reaction mechanism involving dual C-H bond activation as a key step was proposed to account for the present reaction.

Chiral Transient Ligand Enabled Enantioselective Synthesis of Atropisomers Decorated with Unactivated Olefins via a Palladium-Catalyzed C-H Olefination.

Herein, atroposelective synthesis of axially chiral biaryls with unactivated olefins by a palladium-catalyzed C-H olefination using a chiral transient directing group strategy has been disclosed. This protocol is well compatible with a variety of biaryl-2-aldehydes as well as various olefins such as allyl sulfonamides and allyl sulfones to provide the atroposelective olefinated products in synthetically useful yields with excellent enantioselectivities up to >99% ee. In addition, a wide number of axially chiral biaryl alcohols were synthesized by the simple diversification of the products in excellent enantioselectivity.

Palladium-Catalyzed Aerobic Oxidative Spirocyclization of Alkyl Amides with Maleimides via ß-C(sp3)-H Activation.

An efficient method for the synthesis of bicyclic spirodiamine molecules via ß-C(sp3)-H bond activation of aliphatic amides, followed by cyclization with maleimides, has been developed. The reaction proceeds through an amide-directed ß-C(sp3)-H bond activation of alkyl amides and subsequent cyclization with maleimides. The methodology is highly compatible with a wide variety of maleimides. Amides derived from biologically active aliphatic and fatty acids were also found to be highly compatible with the protocol. A palladacycle was synthesized and found to be the active intermediate in this reaction. A plausible reaction mechanism was also proposed to account for this spirocyclization.

Dehydrogenative Cross-Coupling of α,ß-Unsaturated Compounds with Unactivated Olefins via Co(III) Catalysis.

An oxidative cross-coupling of α,ß-unsaturated compounds with unactivated alkenes via cobalt-catalyzed vinylic C-H activation has been developed. The present catalytic reaction was examined with various differently functionalized unsaturated compounds and unactivated olefins. In these reactions, highly valuable amide functionalized butadienes and indenones were prepared in good to excellent yields. A possible reaction mechanism is proposed involving directed olefinic C-H activation through a base-assisted deprotonation pathway.

Co(III)-Catalyzed three-component assembling of N-(2-pyrimidyl) indoles with dienes and formaldehyde.

A highly regio- and chemoselective three-component assembling of N-pyrimidyl indoles with dienes and formaldehyde in the presence of a Co(III) catalyst was demonstrated. The scope of the reaction was investigated with a variety of indole derivatives to synthesize substituted homoallylic alcohols. Both butadiene and isoprene units were compatible with the reaction. To understand the reaction mechanism, various investigations were carried out, and suggested the plausibility of a reaction mechanism involving C-H bond activation as a key step.

One-Pot Synthesis of Benzo[c]phenanthridine Alkaloids from 7-Azabenzonorbornadienes and Aryl Nitrones.

An efficient synthesis of benzo[c]phenanthridine alkaloids via a synergistic combination of C-C bond formation and a cycloaromatization reaction is described. Aryl nitrones react with 7-azabenzonorbornadienes in the presence of a Rh(III) catalyst, providing pharmaceutically useful benzo[c]phenanthridine derivatives in good to moderate yields. Using this methodology, highly useful alkaloids such as norfagaronine, norchelerythrine, decarine, norsanguinarine, and nornitidine were prepared in a single step.

Palladium-catalyzed stereocontrolled ring-opening of 7-oxabenzonorbornadienes with organic carboxylic acids.

A palladium-catalyzed tandem reaction of 7-oxabenzonorbornadienes with organic carboxylic acids that provides cis-1,2-dihydro-l-naphthyl derivatives in moderate to good yields in a highly diastereoselective manner is described. A possible reaction mechanism involving syn acylation followed by insertion and diastereoselective ring-opening with 7-oxabenzonorbornadienes is proposed to account for the reaction.

Synthesis of Selenoflavones via Ruthenium-Catalyzed Selenylation of Unsaturated Acids.

An efficient method for pharmaceutically useful selenoflavones via a ruthenium-catalyzed selenylation reaction is demonstrated. The ruthenium-catalyzed selenylation was applied to synthesize diverse alkenyl selenides from simple unsaturated acids/amides and diaryl diselenides. A wide range of differently substituted diaryl diselenides can be applied in this protocol with a good functional group with excellent stereo- and regioselectivity.

Palladium-Catalyzed [3 + 2] Annulation of Aromatic Amides with Maleimides through Dual C-H Activation.

A palladium-catalyzed [3 + 2] annulation of substituted aromatic amides with maleimides providing tricyclic heterocyclic molecules in good to moderate yields through weak carbonyl chelation is reported. The reaction proceeds via a dual C-H bond activation where the first C-H activation takes place selectively at the benzylic position followed by a second C-H bond activation at the meta position to afford a five-membered cyclic ring. An external ligand Ac-Gly-OH has been used to succeed in this protocol. A plausible reaction mechanism has been proposed for the [3 + 2] annulation reaction.

Rhodium-Catalyzed Allylic C-H Functionalization of Unactivated Alkenes with α-Diazocarbonyl Compounds.

A redox-neutral mild methodology for the allylic C-H alkylation of unactivated alkenes with diazo compounds is demonstrated. The developed protocol is able to bypass the possibility of the cyclopropanation of an alkene upon its reaction with the acceptor-acceptor diazo compounds. The protocol is highly accomplished due to its compatibility with various unactivated alkenes functionalized with different sensitive functional groups. A rhodacycle π-allyl intermediate has been synthesized and proved to be the active intermediate. Additional mechanistic investigations aided the elucidation of the plausible reaction mechanism.

Ru(II)-Catalyzed C-H Alkenylation of Benzimidates with Unactivated Olefins: A Route to ortho-Alkenylated Benzonitriles.

A Ru(II)-catalyzed C-H alkenylation of benzimidates with unactivated alkenes providing ortho-alkenylated benzonitriles in good to excellent yields in a highly regio- and stereoselective manner is described. In the reaction, an imidate group converted into a nitrile under the reaction conditions. The alkenylation reaction was compatible with various substituted benzimidates as well as functionalized unactivated olefins, including ibuprofen-, neproxen-, coumarin-, and cholesterol-substituted alkenes. A feasible reaction mechanism was proposed to account for the present alkenylation reaction.