Asymmetric Syn-Selective Vinylogous Addition of Butenolides to Chromones via Al-Li-BINOL Catalysis.

A gram-scale syn-selective asymmetric vinylogous addition of butenolides to chromones, catalyzed by an Al-Li-BINOL (ALB) complex, was developed in this study. For various combinations of substrates, the observed diastereoselectivity approached 20:1 with 84-98% ee. This protocol is complementary to previously reported ones and improves the selectivity for several chromones. This methodology can be applied to a quinolone substrate, affording another type of heterocyclic scaffolds substituted with five-membered lactones. Computational studies support the role of ALB as a bifunctional catalyst in this reaction and provide insights into the origin of the observed stereoselectivity.

Ru(II)-Catalyzed Switchable C-H Alkylation and Spirocyclization of 2-Arylquinoxalines with Maleimides via ortho-C-H Activation.

A Ru(II)-catalyzed facile and controllable protocol for C-H alkylation and spirocyclization of 2-arylquinoxalines with maleimides has been achieved under ambient air in high yields. Sequential ortho-C-H activation and C-annulation results in the formation of diverse polyheterocycles containing spiro[indeno[1,2-b]quinoxaline-11,3'-pyrrolidine]-2',5'-diones, which are of potent interest in medicinal chemistry. Mechanistic investigations suggest a reversible cleavage of the ortho-C-H bond in the turnover-limiting step.

Rhodium(iii)-catalyzed ortho-C-H amidation of 2-arylindazoles with a dioxazolone as an amidating reagent.

A simple and efficient method for the directed amidation of a wide range of 2-arylindazoles has been established for the first time through a rhodium-catalyzed C-H activation reaction with alkyl, aryl and heteroaryl dioxazolones. A series of N-(2-(2H-indazol-2-yl)phenyl)acetamide derivatives were synthesized in excellent yields. A mechanistic study was conducted to describe C-H bond cleavage which is likely to be involved in the rate determining step.

Regioselective hydroarylation and arylation of maleimides with indazoles via a Rh(iii)-catalyzed C-H activation.

Switchable Rh(iii)-catalyzed highly regioselective hydroarylation and oxidative arylation of maleimides with 2-arylindazoles via C-H activation have been demonstrated. The reaction affords 3-(2-(2H-indazol-2-yl)phenyl)succinimide and 3-(2-(2H-indazol-2-yl)phenyl)maleimide derivatives in high yields with wide functional group tolerance. A mechanistic study was performed to depict C-H bond cleavage that might be involved in the turnover limiting step.

Fe(iii)-Catalyzed synthesis of steroidal imidazoheterocycles as potent antiproliferative agents.

An efficient and practical method has been developed for the synthesis of steroidal imidazoheterocycles via cost-effective and environmentally benign FeCl3-catalyzed oxidative amination. A library of steroidal imidazo[1,2-a]pyridines was directly synthesized from readily available 2-aminopyridines and steroidal ketones in aerobic conditions. The synthesized compounds were screened for activity on human microsomal cytochrome P450s CYP7, CYP17 and CYP21. Antiproliferative activity of two lead compounds 3ia and 3la was additionally evaluated against the human MCF-7 (breast cancer), SKOV3 (ovarian cancer), and 22Rv1 (prostate cancer) cell lines. Steroidal imidazo[1,2-a]pyridine 3la which is a substrate molecule for CYP17A1 with IC50 = 1.7 µM (MCF-7), 3.0 (SKOV3), and 6.0 µM (22Rv1) has proved to be more active than reference drug cisplatin.

Mn(II)-Catalyzed C-H Alkylation of Imidazopyridines and N-Heteroarenes via Decarbonylative and Cross-Dehydrogenative Coupling.

A Mn(II)-catalyzed efficient C-H alkylation of imidazoheterocycles and N-heteroarenes with aliphatic aldehydes has been developed via oxidative decarbonylation. Other alkylating agents such as cyclic alkanes, ethers, and alcohols also coupled with N-heteroarenes through cross-dehydrogenative coupling. Regioselectively C5-alkylated imidazoheterocycles were synthesized in good yields. Experimental results show that radical pathway might be involved in this reaction.

Divergent Synthesis of Allenylsulfonamide and Enaminonesulfonamide via In(III)-Catalyzed Couplings of Propargylamine and N-Fluorobenzenesulfonimide.

An In(III)-catalyzed facile and controllable method for the synthesis of allenylsulfonamide and enaminonesulfonamide has been achieved by the reaction between propargylamine and N-fluorobenzenesulfonimide (NFSI) under mild conditions. The present protocol is also applicable to the synthesis of tetrasubstituted allenylsulfonamide from triphenyl propargylalcohol. Experimental results suggest that the reaction probably proceeds through the ionic pathway.

Ruthenium-catalyzed tandem annulation/arylation for the synthesis of unsymmetrical bis(heteroaryl)methanes.

A new Ru-catalyzed tandem furan annulation/arylation strategy has been developed to afford unsymmetrical bis(heteroaryl)methanes by a reaction between propargyl amines and indoles. A series of bis(heteroaryl)methanes containing furan and indole as well as indole and imidazopyridine moieties have been synthesized in high yields. The reaction possibly proceeds through furan annulation followed by nucleophilic addition of indole.

A convergent synthesis of vinyloxyimidazopyridine via Cu(i)-catalyzed three-component coupling.

The synthesis of vinyloxyimidazopyridine with complete regio- and stereoselectivity has been achieved by the Cu(i)-catalyzed three-component coupling of 2-aminopyridine, 2-oxoaldehyde and alkyne. This protocol is operationally very simple and has much potential for the synthesis of heteroarylated vinyl ethers from basic chemicals. Steroidal imidazopyridinyl vinyl ether was obtained successfully from ethynylestradiol.

(Diacetoxy)iodobenzene-Mediated Oxidative C-H Amination of Imidazopyridines at Ambient Temperature.

(Diacetoxy)iodobenzene (PIDA)-mediated direct oxidative C-H amination for the synthesis of 3-amino substituted imidazopyridines has been achieved under metal-free conditions at room temperature in short reaction times. This methodology is also applicable for the regioselective amination of indolizines. Experimental results suggest that the reaction likely proceeds through a radical pathway.

Visible Light Organic Photoredox-Catalyzed C-H Alkoxylation of Imidazopyridine with Alcohol.

The visible light-mediated C-3 alkoxylation of imidazopyridines with alcohols has been achieved using rose bengal as an organic photoredox catalyst at room temperature. Widely abundant air acts as the terminal oxidant that avoids the use of a stoichiometric amount of peroxo compounds. A wide range of functional groups could be tolerated under the reaction conditions to produce C(sp2)-H alkoxylated products in high yields.

FeCl3-Catalyzed Cross-Dehydrogenative Coupling between Imidazoheterocycles and Oxoaldehydes.

An Fe(III)-catalyzed efficient dicarbonylation of imidazoheterocycles has been developed through cross-dehydrogenative coupling between imidazoheterocycles and oxoaldehydes under ambient air in high yields. The present protocol is also applicable to indolizines. Imidazopyridine produced bisimidazopyridine with arylaldehyde. Experimental results suggest that the reactions proceed through the nonradical pathway.

Switching the regioselectivity in the copper-catalyzed synthesis of iodoimidazo[1,2-a]pyridines.

A unique copper-catalyzed binucleophilic switching of 2-aminopyridine has been developed for the regioselective synthesis of 2- and 3-iodoimidazo[1,2-a]pyridines using alkenes/alkynes as coupling partners in the presence of molecular iodine under aerobic reaction conditions. This method was also applied to the synthesis of 2-iodo-3-phenylbenzo[d]imidazo[2,1-b]thiazoles. This protocol offers an easy route towards the synthesis of 2,3-diarylimidazo[1,2-a]pyridines.

Direct Catalytic Enantioselective Conjugate Addition of α-Substituted Benzyl Nitriles to Alkyl Acrylates.

The first enantioselective copper-catalyzed conjugate addition of α-substituted benzyl nitriles to alkyl acrylates is described. This protocol allows the direct and 100% atom-economic generation of a nitrile-containing quaternary stereogenic center in a highly enantioselective manner. The practical application of our methodology was demonstrated through the concise formal synthesis of (-)-aphanorphine.

Catalytic Asymmetric Vinylogous Conjugate Addition of Butenolide to 2-Ester-Substituted Chromones: Access to Chiral Chromanone Lactones via Trapping of a Copper(I) Enolate by Trimethyl Borate.

A copper-catalyzed asymmetric vinylogous conjugate addition of butenolide to 2-ester-substituted chromones is described, and it delivers syn- or anti-chromanone lactones with high stereoselectivities. The enantioselectivity-determining step varied with the use of B(OMe)3 as an additive, resulting in enhanced stereoselectivities, as revealed by density functional theory calculations, which also provided theoretical insight into the origin of the ligand-dependent diastereodivergence.

Visible light-induced photocatalytic C-H ethoxycarbonylmethylation of imidazoheterocycles with ethyl diazoacetate.

A visible light-mediated regioselective C3-ethoxycarbonylmethylation of imidazopyridines with ethyl diazoacetate (EDA) was achieved under mild reaction conditions. In contrast to the carbene precursors from α-diazoester a first C3-ethoxycarbonylmethylation of imidazopyridines via a radical intermediate has been established. The present methodology provides a concise route to access pharmacologically useful esters with wide functional group tolerance in high yields.

Organophotoredox-Catalyzed Direct C-H Amination of 2H-Indazoles with Amines.

A general and practical method for the direct C-H amination of 2H-indazoles with a series of amines including aliphatic primary amines, secondary amines, azoles, and sulfoximines via organophotoredox-catalyzed oxidative coupling has been disclosed at room temperature under ambient air conditions. Additionally, this protocol is used for free aminated 2H-indazole synthesis. A mechanistic study revealed that a single electron transfer (SET) pathway might be involved in this reaction.

Rhodium-Catalyzed Directed C-H Amidation of Imidazoheterocycles with Dioxazolones.

A Rh(III)-catalyzed directed ortho-amidation of 2-arylimidazoheterocycles using dioxazolone as an amidating reagent has been developed. This protocol is a simple, straightforward, and economic was to afford a variety of N-(2-(imidazo[1,2- a]pyridin-2-yl)phenyl)acetamide derivatives with excellent yields. A mechanistic study reveals that a reversible cleavage of C-H bond might be involved in the reaction.

Regioselective synthesis of unsymmetrical biheteroaryls via copper(ii)-catalyzed cascade annulation.

A facile and efficient copper-catalyzed cascade annulation of an imidazoheterocycle with salicylaldehyde, piperidine, and terminal alkyne was developed to afford unsymmetrical biheteroaryl derivatives. A variety of biheteroaryl structural motifs containing furans and imidazoheterocycles have been synthesized in ambient air in high yields. The experimental results suggest that the reaction proceeds through a sequential non-radical 5-exo-dig cyclization process.

Metal-free C-H arylation of imidazoheterocycles with aryl hydrazines.

A simple and efficient metal-free arylation of imidazo[1,2-a]pyridines at the C-3 position with arylhydrazine has been achieved at room temperature under ambient air conditions. Various 2,3-disubstituted imidazopyridines and imidazothiazoles were synthesized with high yields. The present methodology demonstrates the usefulness of commercially available aryl hydrazine as an arylating agent.