Cobalt(III)‐Catalyzed Redox‐Neutral Synthesis of Unprotected Indoles Featuring an N−N Bond Cleavage

A redox‐neutral cobalt(III)‐catalyzed synthetic approach for the direct synthesis of unprotected indoles showcasing an N?N bond cleavage is reported. The herein newly introduced Boc‐protected hydrazines establish a beneficial addition to the limited portfolio of oxidizing directing groups for cobalt(III) catalysis. Moreover, the developed catalytic methodology tolerates a good variety of functional groups.     

Nickel‐Catalyzed Asymmetric Reductive 1,2‐Carboamination of Unactivated Alkenes

Starting from diverse alkene‐tethered aryl iodides and O‐benzoyl‐hydroxylamines, the enantioselective reductive cross‐electrophilic 1,2‐carboamination of unactivated alkenes was achieved using a chiral pyrox/nickel complex as the catalyst. This mild, modular, and practical protocol provides rapid access to a variety of β‐chiral amines with an enantioenriched aryl‐substituted quaternary carbon center in good yields and with excellent enantioselectivities. This process reveals a complementary regioselectivity when compared to Pd and Cu catalysis.     

Intermolecular 1,4‐Carboamination of Conjugated Dienes Enabled by Cp*RhIII‐Catalyzed C−H Activation

A protocol for the three‐component 1,4‐carboamination of dienes is described. Synthetically versatile Weinreb amides were coupled with 1,3‐dienes and readily available dioxazolones as the nitrogen source using [Cp*RhCl₂]₂‐catalyzed C?H activation to deliver the 1,4‐carboaminated products. This transformation proceeds under mild reaction conditions and affords the products with high levels of regio‐ and E‐selectivity. Mechanistic investigations suggest an intermediate Rh^III–allyl species is trapped by an electrophilic amidation reagent in a redox‐neutral fashion.     

Iridium(III)‐Catalyzed Regioselective Intermolecular Unactivated Secondary Csp3−H Bond Amidation

For the first time, a highly regioselective intermolecular sulfonylamidation unactivated secondary Csp³?H bond has been achieved using Ir^III catalysts. The introduced N,N’‐bichelating ligand plays a crucial role in enabling iridium–nitrene insertion into a secondary Csp³?H bond via an outer‐sphere pathway. Mechanistic studies and density functional theory (DFT) calculations demonstrated that a two‐electron concerted nitrene insertion was involved in this Csp³?H amidation process. This method tolerates a broad range of linear and branched‐chain N‐alkylamides, and provides efficient access to diverse γ‐sulfonamido‐substituted aliphatic amines.     

Cp*Co(III)-catalyzed CH amidation of azines with dioxazolones

Cp*Co(III)-catalyzed direct CH amidation of azines has been developed. This conversion could proceed smoothly in the absence of external oxidants, acids or bases, with excellent regioselectivity and broad functional group tolerance. CO₂ was released as the sole byproduct, thus providing an environmentally benign amidation process. The products obtained are important intermediates in organic synthesis.     

Chiral Carboxylic Acid Enabled Achiral Rhodium(III)‐Catalyzed Enantioselective C−H Functionalization

Reported is an achiral Cp^xRh^III/chiral carboxylic acid catalyzed asymmetric C?H alkylation of diarylmethanamines with a diazomalonate, followed by cyclization and decarboxylation to afford 1,4‐dihydroisoquinolin‐3(2H)‐one. Secondary alkylamines as well as nonprotected primary alkylamines underwent the transformation with high enantioselectivities (up to 98.5:1.5 e.r.) by using a newly developed chiral carboxylic acid as the sole source of chirality to achieve enantioselective C?H cleavage by a concerted metalation‐deprotonation mechanism.     

Synthesis and Biological Studies on (KLAKLAK)2-NH2 Analog Containing Unnatural Amino Acid β-Ala and Conjugates with Second Pharmacophore

(1) Background: Peptides are good candidates for anticancer drugs due to their natural existence in the body and lack of secondary effects. (KLAKLAK)₂ is an antimicrobial peptide that also shows good anticancer properties. (2) Methods: The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of target molecules, analogs of (KLAKLAK)₂-NH₂. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. For determination of antimicrobial activity, the disc-diffusion method was used. Hydrolytic stability at three pH values, which mimic the physiological pH in the body, was investigated by means of the HPLC technique. (3) Results: A good selective index against MCF-7 tumor cell lines, combined with good cytotoxicity and antiproliferative properties, was revealed for conjugates NphtG-(KLAKLAK)₂-NH₂ and Caf-(KLAKLAK)₂-NH₂. The same compounds showed very good antifungal properties and complete hydrolytic stability for 72 h. The compound Caf-(KLβ-AKLβ-AK)₂-NH₂ containing β-Ala in its structures exhibited good antimicrobial activity against Escherichia coli K12 407 and Bacillus subtilis 3562, in combination with very good antiproliferative and cytotoxic properties, as well as hydrolytic stability. (4) Conclusions: The obtained results reveal that all synthesized conjugates could be useful for medical practice as anticancer or antimicrobial agents.     

Cp*Co(III)-catalyzed C-H amidation of azines with dioxazolones

Cp^*Co(III)-catalyzed direct C-H amidation of azines has been developed. This conversion could proceed smoothly in the absence of external oxidants, acids or bases, with excellent regioselectivity and broad functional group tolerance. CO₂ was released as the sole byproduct, thus providing an environmentally benign amidation process. The products obtained are important intermediates in organic synthesis.     

Asymmetric Synthesis of Unnatural Amino Acids and Tamsulosin Chiral Intermediate

An efficient and enantioselective hydrogenation of N-acetylamino phenyl acrylic acids was successfully developed by using ruthenium catalyst. This methodology is important in the field of pharmaceuticals and provides a new process for the preparation of unnatural amino acids and tamsulosin chiral intermediate.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]     

Intermolecular Interactions in Systems Containing Bi(III) – ClO−4 – H2O – Selected Amino Acids in the Aspect of Catalysis of Bi(III) Electroreduction

The paper describes recent results of studies on the accelerating effect of sulfur‐containing protein amino acids and water activity on multistep Bi(III) ion electroreduction at mercury electrode. The catalytic effect of methionine (Mt), cystine (CY) and cysteine (CE) was analyzed based on kinetic and thermodynamic parameters, which correlated with water activity. Investigations of adsorption of those amino acids at the electrode/solution interface provided information for the analysis of the electrical double layer and its influence on the kinetics of the electrode process. The multistep Bi(III) electroreduction process is controlled by the kinetics of active complexes formation, which precedes transfer of consecutive electrons.     

Phase‐Transfer‐Catalyzed Asymmetric SNAr Reaction of α‐Amino Acid Derivatives with Arene Chromium Complexes

Although phase‐transfer‐catalyzed asymmetric S_NAr reactions provide unique contribution to the catalytic asymmetric α‐arylations of carbonyl compounds to produce biologically active α‐aryl carbonyl compounds, the electrophiles were limited to arenes bearing strong electron‐withdrawing groups, such as a nitro group. To overcome this limitation, we examined the asymmetric S_NAr reactions of α‐amino acid derivatives with arene chromium complexes derived from fluoroarenes, including those containing electron‐donating substituents. The arylation was efficiently promoted by binaphthyl‐modified chiral phase‐transfer catalysts to give the corresponding α,α‐disubstituted α‐amino acids containing various aromatic substituents with high enantioselectivities.     

Cationic Cobalt(III) Catalyzed Indole Synthesis: The Regioselective Intermolecular Cyclization of N‐Nitrosoanilines and Alkynes

The unique regioselectivity and reactivity of cobalt(III) in the direct cyclization of N‐nitrosoanilines with alkynes for the expedient synthesis of N‐substituted indoles is demonstrated. In the presence of a cobalt(III) catalyst, high regioselectivity was observed when using unsymmetrical meta‐substituted N‐nitrosoanilines. Moreover, internal alkynes bearing electron‐deficient groups, which are almost unreactive in the [Cp*Rh^III]‐catalyzed system, display good reactivity in this transformation.     

Highly Efficient Synthesis of Heterocyclic and Alicyclic β2‐Amino Acid Derivatives by Catalytic Asymmetric Hydrogenation

A valuable class of new heterocyclic and alicyclic prochiral α‐aminomethylacrylates has been conveniently synthesized through a three‐step transformation involving a Baylis–Hillman reaction, O‐acetylation, and a subsequent allylic amination. The corresponding novel β²‐amino acid derivatives were prepared with excellent enantioselectivities and high yields by catalytic asymmetric hydrogenation using the catalyst rhodium(Et‐Duphos) (Et‐Duphos=2′,5′,2′′,5′′‐tetraethyl‐1,2‐bis(phospholanyl)benzene)) under mild reaction conditions (up to 99 % ee and S/C=1000). The influence of the substrate on the enantioselectivity and reactivity is investigated, and the most suitable substrate configuration for the highly efficient enantioselective hydrogenation of β‐substituted α‐aminomethylacrylates under the Rh–Duphos system is reported. The current protocol provides a very practical, facile, and scalable method for the preparation of heterocyclic and alicyclic β²‐amino acids and their derivatives.     

Copper‐Catalyzed Regioselective Borocarbonylative Coupling of Unactivated Alkenes with Alkyl Halides: Synthesis of β‐Boryl Ketones

The borocarbonylative coupling of unactivated alkenes with alkyl halides remains a challenge. In this communication, a Cu‐catalyzed borocarbonylative coupling of unactivated alkenes with alkyl halides for the synthesis of β‐boryl ketones has been developed. A broad range of β‐boryl ketone derivatives was prepared in moderate to excellent yields with complete regioselectivity.     

Metal‐Catalyzed Derivatization of Cα‐Tetrasubstituted Amino Acids and Their Use in the Synthesis of Cyclic Peptides

Making circles with N and O : Cyclic tripeptides containing an unnatural C^α‐tetrasubstituted THF amino acid are prepared by copper(I) and palladium(0)‐catalyzed N‐ and O‐arylation reactions. The reactions give access to side chain‐modified derivatives of the unnatural amino acid and macrocyclic peptidomimetics.

     

The Reductions of Bis(terpyridyl) and Ethylenediaminetetraacetato Complexes of Cobalt(III) by Ascorbic Acid

The reductions of Co(terpy)₂³⁺ and Co(edta)^? complexes by ascorbic acid have been subjected to a detailed kinetic study in the range of pH =1–10.9. For each complex the rate law of the reaction is interpreted as a rate determining reaction between Co(III) complex and the ascorbic acid in the form of HA^? (k₁) and A^2? (k₂), depending on the pH of the solution, followed by a rapid scavenge of the ascorbic acid radicals by Co(III) complex. With given Ka₁ and Ka₂, the rate constants are k₁ = 0.25 and 9.87 × 10^?5 M^?1s^?1, k₂ = 1.28 × 10⁶ and 18.7 M^?1s^?1 for Co(terpy₎2³⁺and Co(edta)^? complexes, respectively, at T = 25 °C and μ = 0.50M (terpy)and 1.0 M (edta) HClO₄/LiClO₄. The mechanism of the reaction is discussed on the basis of Marcus theory for outer sphere electron transfer process. Spin change and charge effect, duly considered, account for the non‐adiabatic behavior in the reduction of Co(edta)^? complex.     

Theoretical prediction on the synthesis of 2,3‐dihydropyridines through Co(III)‐catalysed reaction of unsaturated oximes with alkenes

Cobalt‐based catalysts can replace the homologous group‐9 rhodium‐based ones. Herein, we used density functional theory (DFT) calculations to predict the synthesis of 2,3‐dihydropyridines using α,β‐unsaturated oxime pivalates and alkenes catalysed by [Cp*CoOAc]⁺ instead of [Cp*RhOAc]⁺. The catalytic cycle involves reversible acetate‐assisted metalation‐deprotonation, migratory insertion of alkenes, and reductive elimination/N‐O cleavage. The migratory insertion of alkenes was determined to be the rate‐determining step, and the reaction is irreversible due to the strongly exergonic reductive elimination/N? O cleavage. When using the CF₃‐substituted Cp*Co(III) catalyst, the apparent activation energy indicates that the title reaction can proceed at higher temperatures. Electron‐withdrawing substituent groups on Cp* facilitate the reaction. In contrast, substituting phenyl with the electron‐deficient p‐CF₃‐phenyl at the 2‐position of α,β‐unsaturated oxime pivalate hinders the reaction, and so does the use of polarized alkenes with electron‐withdrawing substituent groups