Eco-friendly Cu/NiO nanoparticle synthesis: Catalytic potential in isatin-based chalcone synthesis for anticancer activity.

Isatin (1H-indole-2,3­dione) is a natural heterocyclic compound extracted from various plants and has biological activity as an anticancer agent. Chalcones with the addition of several functional groups (hydroxyl, carboxyl, phenyl, etc.) may become useful templates for the development of new anticancer agents. In this study, we have synthesized Cu/NiO nanoparticles using the sol-gel method involving annona muricata L leaf extract and used as catalysts for the synthesis of isatin-based chalcone. These compounds will be applied as anticancer agents against MCF-7 cancer cell. According to the characterization results using FT-IR, XRD, FESEM-EDS, the crystal size for Cu/NiO nanoparticles was 5.4566 nm and the particle size was 25.081 ± 8.422 nm with irregular spherical shapes. The synthesis of isatin based on chalcone using the reflux method refers to the claisen schmidt condensation reaction using 5% mmol Cu/NiO nanoparticles resulting in yields for each product of 50 % (product 1), 32.37 % (product 2), 24.29 % (product 3), 32.35 % (product 4), 50.86 % (product 5), and 69.88 % (product 6). The effectiveness of the six products against MCF-7 cancer cells can be seen from the IC50 values as follows product 1 (IC50 = 0.00157 µg/ml), product 2 (IC50 = 100.897 µg/ml), product 3 (IC50 = 81.991 µg/ml), product 4 (IC50 = 8107.54 µg/ml), product 5 (IC50 = 77.9291 µg/ml), product 6 (IC50 = 25.4521 µg/ml). Based on the IC50 value obtained, it shows that product 1 and product 6 have strong activity when compared to another product on against MCF-7 cancer cells. •Acetophenone as a simple ketone was modified to 2-acetylpyridine.•Modification was performed adding Cu/NiO nanoparticle as catalyst.•Final products exhibited anticancer activity (MCF-7).

Visible-Light Photoredox-Catalyzed Giese Reaction of α-Silyl Ethers with Various Michael Acceptors.

We developed a photocatalyzed Giese reaction of various weakly activated Michael acceptors with a neutral silicon-based radical precursor and applied it at large-scale using a continuous flow reactor. The developed method successfully overcomes the substrate scope limitations of previous studies, shows good functional groups tolerance, and affords good to excellent yields. On the basis of mechanistic studies, we propose a reaction mechanism that involves an in situ generated alkoxymethyl radical via single-electron oxidation of α-trimethylsilyl-substituted ethers.

Photoredox-Catalyzed Synthesis of ß-Amino Alcohols: Hydroxymethylation of Imines with α-Silyl Ether as Hydroxymethyl Radical Precursor.

Carbon-carbon bond formation is an efficient approach for the synthesis of amino alcohols using two simple starting materials. Herein, we present a novel method for a divergent synthesis of ß-amino ethers and ß-amino alcohols in a sequential one-pot protocol under high-efficiency, mild, and metal- or metal-free conditions. Especially, TMSCH2OPMP was developed as a synthetic equivalent of α-hydroxymethyl radical in an in situ photocatalyzed oxidative PMP group deprotection strategy under air. A preliminary mechanistic investigation provides evidence for reaction mechanism involving a photoinduced α-alkoxy methyl radical and superoxide.

KOtBu-promoted C3-homocoupling of quinoxalinones through single electron transfer from an sp2 carbanion intermediate.

The C3-selective homodimerization of quinoxalinones is described. A C3-sp2 carbanion species generated through deprotonation of quinoxalinone using potassium tert-butoxide (KOtBu) transfers an electron (single electron transfer mechanism) to a second quinoxalinone, affording a radical-anion intermediate. The radical scavenging and electron paramagnetic resonance (EPR) experiments support the plausible radical reaction pathway. A mild reaction temperature and a short reaction time were attained under cost-effective conditions, which reveal the amenability of this protocol to pharmaceutical and chemical industries.

Weak base-promoted selective rearrangement of oxaziridines to amides via visible-light photoredox catalysis.

The selective rearrangement of oxaziridines to amides via a single electron transfer (SET) pathway is unexplored. In this study, we present a weak base-promoted selective rearrangement of oxaziridines to amides via visible-light photoredox catalysis. The developed method shows excellent functional group tolerance with a broad substrate scope and good to excellent yields. Furthermore, control experiments and density functional theory (DFT) calculations are performed to gain insight into the reactivity and selectivity.

Controllable one-pot synthesis for scaffold diversity via visible-light photoredox-catalyzed Giese reaction and further transformation.

This study presents a controllable one-pot synthesis for constructing valuable scaffolds (alcohols, 2,3-dihydrofurans, α-cyano-γ-butyrolactones, and γ-butyrolactones) via a visible-light photoredox-catalyzed Giese reaction and further transformation. This one-pot reaction can selectively synthesize the desired scaffold in excellent yields with good functional group tolerance. To further highlight the broad applicability of this controllable one-pot reaction, we have established flow reaction conditions with short reaction times for the scale-up of each scaffold and demonstrated the further transformation of 2,3-dihydrofurans and α-cyano-γ-butyrolactones to achieve scaffold diversity for applications in drug discovery.

Catalytic Enantioselective Carbonyl Propargylation Beyond Preformed Carbanions: Reductive Coupling and Hydrogen Auto-Transfer.

Chiral metal complexes catalyze enantioselective carbonyl propargylation via reductive coupling or as hydrogen auto-transfer processes, in which reactant alcohols serve dually as reductant and carbonyl proelectrophile. Unlike classical propargylation protocols, which rely on allenylmetal reagents or metallic reductants (e.g. NHK reactions), reductive protocols for carbonyl propargylation can occur in the absence of stoichiometric metals, precluding generation of metallic byproducts. Propargylations of this type exploit both enyne and propargyl halide pronucleophiles.

Oxidative Deprotection of p-Methoxybenzyl Ethers via Metal-Free Photoredox Catalysis.

An efficient and greener deprotection method for p-methoxybenzyl (PMB) ethers using a metal-free visible light photoredox catalyst and air and ammonium persulfate as the terminal oxidants is presented. Various functional groups and protecting groups were tolerated in the developed method to achieve good to excellent yields in short reaction times. Significantly, the developed method was compatible with PMB ethers derived from primary, secondary, and tertiary alcohols and a gram-scale reaction. Mechanistic studies support a proposed reaction mechanism that involves single electron oxidation of the PMB ether.

Visible-Light Photoredox-Catalyzed Hydroalkoxymethylation of Activated Alkenes Using α-Silyl Ethers as Alkoxymethyl Radical Equivalents.

A new neutral silicon-based traceless activation group (TAG) for visible-light photoredox-catalyzed hydroalkoxymethylation of alkenes is presented. This reaction involves in-situ-generated alkoxymethyl radical via single electron oxidation (SET) of α-TMS-substituted ethers, followed by subsequent conjugate addition to activated alkenes. Various functional groups were tolerated both under mild metal and metal-free conditions to provide good to excellent yields. Furthermore, the addition products were transformed to valuable synthetic building blocks, such as carboxylic acids, γ-butyrolactones, and complex aryl alkyl ethers.

Synthesis of 4-Isoxazolines via Visible-Light Photoredox-Catalyzed [3 + 2] Cycloaddition of Oxaziridines with Alkynes.

A method for [3 + 2] cycloaddition of oxaziridines with alkynes to form 4-isoxazolines via visible-light photoredox catalysis is described. This method is a greener, atom-economical reaction that tolerates various functional groups and provides good to excellent yield. Moreover, the cyclization products can be conveniently converted into tetrasubstituted allylic alcohols and enamines. A mechanistic study suggests that the reaction involves photoredox-catalyzed in situ generation of a nitrone from the oxaziridine by SET.

C-Propargylation Overrides O-Propargylation in Reactions of Propargyl Chloride with Primary Alcohols: Rhodium-Catalyzed Transfer Hydrogenation.

The canonical SN 2 behavior displayed by alcohols and activated alkyl halides in basic media (O-alkylation) is superseded by a pathway leading to carbinol C-alkylation under the conditions of rhodium-catalyzed transfer hydrogenation. Racemic and asymmetric propargylations are described.

Correction: One-pot synthesis of carbazoles via tandem C-C cross-coupling and reductive amination.

Correction for 'One-pot synthesis of carbazoles via tandem C-C cross-coupling and reductive amination' by Deuk-Young Goo, et al., Org. Biomol. Chem., 2016, DOI: 10.1039/c5ob01952d.

One-pot synthesis of carbazoles via tandem C-C cross-coupling and reductive amination.

We have developed a highly efficient synthetic route to carbazoles that employs sequential C-C/C-N bond formation via Suzuki cross-coupling and Cadogan cyclization using commercially available or easily preparable starting materials. The developed method is compatible with electron neutral, rich or deficient substrates. The synthetic utility of this method was demonstrated by the concise syntheses of four natural products (glycozoline, glycozolicine, glycozolidine and clausenalene).

Total synthesis of 6-deoxyerythronolide B via C-C bond-forming transfer hydrogenation.

The 14-membered macrolide 6-deoxyerythronolide B is prepared in 14 steps (longest linear sequence) and 20 total steps. Two different methods for alcohol CH-crotylation via transfer hydrogenation are deployed for the first time in target-oriented synthesis. Enyne metathesis is used to form the 14-membered ring. The present approach represents the most concise construction of any erythronolide reported, to date.

Enantioselective carbonyl propargylation by iridium-catalyzed transfer hydrogenative coupling of alcohols and propargyl chlorides.

It takes alkynes! Exposure of propargyl chlorides to primary benzylic alcohols in the presence of [Ir(cod){(R)-segphos}]OTf (cod = 1,5-cyclooctadiene, segphos = 5,5'-bis(diphenylphosphino)-4,4'-bi-1,3-benzodioxole, Tf = trifluoromethanesulfonyl) results in hydrogen exchange to give allenyliridium-aldehyde pairs that combine to form products of propargylation with high ee value (see scheme). The reaction can also be conducted using aldehydes.

Total synthesis of bryostatin 7 via C-C bond-forming hydrogenation.

The marine macrolide bryostatin 7 is prepared in 20 steps (longest linear sequence) and 36 total steps with five C-C bonds formed using hydrogenative methods. This approach represents the most concise synthesis of any bryostatin reported, to date.

Polycavernoside A: the Prins macrocyclization approach.

An intramolecular Prins macrocyclization reaction was successfully employed in the synthesis of polycavernoside A.

Stereoselective synthesis of (-)-amphidinolide E.

The total synthesis of (-)-amphidinolide E was accomplished by following a synthetic scheme that incorporates the labile C2 stereocenter at a very late stage. The oxolane unit was prepared by beta-alkoxyacrylate radical cyclization. The enyne metathesis reaction was employed for the synthesis of the side chain. The Kocienski-Julia reaction was used for the union of the two major fragments, and the Kita macrolactonization protocol was used for macrolide synthesis.