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3-Methyl-5-benzofuranol was prepared by a one-pot process from morpholine, propionaldehyde, and p-benzoquinone in 85–87% isolated yields. Avoiding the tedious multistep isolation and purification o...

The laboratory experiment regarding esterification of ethylene glycol with acetic acid to ethylene glycol diacetate using resin catalysts in a continuous flow was designed to carry out the reaction in a flow through an inquiry-guided approach. Incorporating the burgeoning field of continuous flow chemistry into the educational infrastructure, the experiment showed the practical application of heterogeneous catalysts in continuous flow synthesis. In a discussion of the importance of continuous flow chemistry and heterogeneous catalysis, students were encouraged to seek effective, sustainable, and environmentally friendly approaches to synthesize compounds.

2-Pyridyl ketones widely appear in bioactive molecules, natural products, and are employed as precursors of chiral 2-pyridine alky/aryl alcohols or 2-aminoalkyl pyridine ligands for asymmetric catalysis. Herein, a practical method for the rapid synthesis of 2-pyridyl ketone library in continuous flow is reported, in which the 2-lithiopyridine formed by Br/Li exchange reacts with commercially available esters to obtain 2-pyridyl ketones in a good yield at short reaction time. This protocol functions broadly on a variety of esters and has been applied to the synthesis of TGF-β type 1 receptor inhibitor LY580276 intermediate in an environmentally friendly method. It is rapid, reliable, and cost-efficient to afford diverse kinds of 2-pyridyl ketones in the compound library.

Variable-temperature 15N solid-state NMR spectroscopy is used to uncover the dynamics of three diamines appended to the metal-organic framework Mg2(dobpdc) (dobpdc4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate), an important family of CO2 capture materials. The results imply both bound and free amine nitrogen environments exist when diamines are coordinated to the framework open Mg2+ sites. There are rapid exchanges between two nitrogen environments for all three diamines, the rates and energetics of which are quantified by 15N solid-state NMR data and corroborated by density functional theory calculations and molecular dynamics simulations. The activation energy for the exchange provides a measure of the metal-amine bond strength. The unexpected negative correlation between the metal-amine bond strength and CO2 adsorption step pressure reveals that metal-amine bond strength is not the only important factor in determining the CO2 adsorption properties of diamine-appended Mg2(dobpdc) metal-organic frameworks.

A metal-free convergent paired electrolysis strategy to synthesize benzylic amines through direct arylation of tertiary amines and benzonitrile derivatives at room temperature has been developed. This TEMPO-mediated electrocatalytic reaction makes full use of both anodic oxidation and cathodic reduction without metals or stoichiometric oxidants, thus showing great potential and advantages for practical synthesis. This convergent paired electrolysis method provides a straightforward and powerful means to activate C-H bonds and realize cross-coupling with cathodically generated species.

We report the first electrochemical strategy to synthesize functionalized naphthalene derivatives through [4+2] annulation-rearrangement-aromatization from styrenes under mild conditions. The electrolysis does not require metals, oxidants and high valence substrates, indicating the atom and step-economy ideals. The dehydrodimer produced through [4+2] cycloaddition of 4-methoxy α-methyl styrene is isolated and proved to be the key intermediate for the following oxydehydrogenation to form carbon cation, which undergoes rearrangement-aromatization to afford the final products. This reaction represents a powerful access to construct multi-substituted naphthalene blocks in a single step.

Transition-metal-free visible-light photoredox catalyzed decarboxylative radical addition has been developed for the construction of α,β-diamino esters from amino acids with glyoxylic oxime ethers under mild conditions. Cyclic and chain amino acids, dipeptides, and simple aliphatic acids are amenable to this addition as the alkyl radical source. A variety of α,β-diamino esters with broad functional groups were synthesized in satisfactory yields at room temperature. The employment of acridinium as the photocatalyst and its potential scalability also demonstrate the synthetic value in practice.

An effective aza-Mannich reaction between olefinic rhodanines/hydantoins and N-Boc aminals catalyzed by Bronsted acid has been developed. Multifunctional rhodanine/hydantoin derivatives were obtained in 71–86% yields and an up to 95/5 Z/E ratio under mild conditions.

A convenient method mediated by photoredox catalysis for the direct construction of 1,4-dicarbonyl compounds has been developed. Simple aromatic symmetric carboxylic anhydrides or mixed anhydrides (generated in situ) have been utilized as an acyl radical source in addition to different types of Michael acceptors. A wide range of substrates are amenable to this new type of acyl Michael addition under mild conditions with broad functional group tolerance. As an application, a novel four-step synthesis of medicinal agent haloperidol is also presented.

Metal–organic frameworks that flex to undergo structural phase changes upon gas adsorption are promising materials for gas storage and separations, and achieving synthetic control over the pressure at which these changes occur is crucial to the design of such materials for specific applications. To this end, a new family of materials based on the flexible metal–organic framework Co(bdp) (bdp2– = 1,4-benzenedipyrazolate) has been prepared via the introduction of fluorine, deuterium, and methyl functional groups on the bdp2– ligand, namely, Co(F-bdp), Co(p-F2-bdp), Co(o-F2-bdp), Co(D4-bdp), and Co(p-Me2-bdp). These frameworks are isoreticular to the parent framework and exhibit similar structural flexibility, transitioning from a low-porosity, collapsed phase to high-porosity, expanded phases with increasing gas pressure. Powder X-ray diffraction studies reveal that fluorination of the aryl ring disrupts edge-to-face π–π interactions, which work to stabilize the collapsed phase at low gas pressures, while d...

The chiral primary amine catalyzed asymmetric Michael reaction of thiazolones and α,β-unsaturated ketones was reported. Two different optimal catalytic systems were obtained corresponding to cyclic and linear α,β-unsaturated ketones. By employing chiral primary amines as the catalysts and amino-acid derivatives as the additives, a variety of Michael adducts containing the scaffold of the thiazole ring were prepared in moderate to good yields and with excellent diastereo- and enantioselectivities (up to 95% yield, all up to >19/1 dr, up to 96% ee). The reaction was scaled up to obtain 1.73 grams of the Michael adduct with the maintenance of yield and stereoselectivity.

An array of organic bases DMAP (4-dimethylaminopyridine), DBU (1, 8-diazabicyclo [5.4.0] undec-7-ene), TBD (1, 5, 7-triazabicyclo [4.4.0] dec-5-ene), and their base/acid conjugate organocatalyst systems were evaluated in the trimerization of various isocyanates. The performance depended greatly on the combination of the catalyst systems, and the [HTBD][OAc] (acetic acid) catalyst systems were considerably the most active in contrast to the corresponding DMAP and DBU counterparts. The [HTBD][OAc] catalyst system was capable of providing isocyanurates from the cyclotrimerization of various isocyanate substrates in excellent yields in seconds even under bulk conditions. A bifunctional catalytic mechanism over [HTBD][OAc] was proposed.

Efficient synthesis of styrenyl enamides can be achieved from the corresponding 4-aryl-2-oxazolidinones, 2-thioxooxazolidines, and 2-thioxothiazolidines in the presence of the strong base lithium diisopropylamine. The reaction proceeded efficiently to achieve the enamides in good to excellent yields (up to 92%). This reaction provides an easy, rapid, and good-yielding method for the synthesis of styrenyl enamides.

A tert-leucine-derived chiral diamine catalyzes the asymmetric Michael addition of nitromethane to five-, six-, and seven-membered β-substituted cyclic enones with excellent enantioselectivity, offering scalable, asymmetric access to all-carbon quaternary stereocenters. The reaction scope can be expanded to include linear acyclic enones, and excellent levels of enantioselectivity are also observed. Furthermore, this organocatalytic, asymmetric nitro-Michael reaction is amenable to multigram scale-up and applications in the construction of an eudesmane sesquiterpenoid skeleton.

We report herein an efficient, general and green method for decarboxylative fluorination of aliphatic carboxylic acids. By using a transition-metal-free, organocatalytic photoredox system, the reaction of various aliphatic carboxylic acids with the Selectfluor reagent afforded the corresponding alkyl fluorides in satisfactory yields under visible light irradiation at room temperature.

The first example of a highly enantioselective and scalable formal diaza-ene reaction between N-monosubstituted hydrazones and enones catalyzed by a simple chiral primary-second diamine salt has been developed. The catalytic process provides a highly practical and stereoselective synthetic method for chiral hydropyridazines.

A highly enantioselective synthesis of spirocycles and bridged rings has been developed through a formal [4 + 2] cycloaddition reaction between enones and N-sulfonylimines. The unprecedented strategy has been realized utilizing N-sulfonylimine as a novel dienophile through enamine–iminium tautomerism of N-sulfonylimine. In addition, a γ,e-regioselective cycloaddition reaction proceeded by employing methylene chromene species as dienophiles.

Efficient synthesis of styrenyl enamides can be achieved from the corresponding 4-aryl-2-oxazolidinones, 2-thioxooxazolidines, and 2-thioxothiazolidines in the presence of the strong base lithium diisopropylamine. The reaction proceeded efficiently to achieve the enamides in good to excellent yields (up to 92%). This reaction provides an easy, rapid, and good-yielding method for the synthesis of styrenyl enamides.

Asymmetric organocatalytic Michael/α-alkylation reactions of α,β-unsaturated aldehydes with chloroacetophenones have been developed. The biologically useful cyclopropane motifs were synthesized with high yields and up to >99% ee, >30:1 dr through Jorgensen–Hayashi catalyst under mild conditions.

Reaction of lactam (I) with α,β-unsaturated ketones provides Michael adducts with high diastereo- and enantioselectivity.

An asymmetric organocatalytic cascade reaction which can afford a series of oxazolidine derivatives has been developed. The one-pot reaction reported here can produce an oxazolidine derivative in a highly enantioselective manner and good yield with good to excellent diastereomeric ratio.

An easy one-pot, multistep cascade reaction which could afford a series of substituted benzo[d]pyrido[2,1-b]oxazolidine and [1,3]oxazine derivatives in a highly enantio- (up to 98% ee) and diastereoselective (4:1 to >20:1 dr) manner with generally good to excellent yields (up to 99%) has been developed. This well designed strategy could be applied to a wide scope of substrates under mild conditions with simple operations.

The conjugate addition of Ni(II) complexes of glycine Schiff base to α,β-unsaturated aldehydes catalyzed by (S)-2-(diphenyl(trimethylsilyloxy)methyl)pyrrolidine afforded adducts in excellent yields with up to 49:1 dr and 95% ee. This method enables the construction of two adjacent chiral centers in one step, and offers an alternative route to chiral α-amino acid derivatives.

Palladium-catalyzed asymmetric 1,6-addition of diarylphosphines to electron-deficient dienes was developed through rational selection of electron-withdrawing groups on the dienes. Various chiral allylic phosphine derivatives were synthesized in good yields with high enantioselectivity (up to 96% ee).

The Michael addition of α,β-unsaturated ketone with triazole was efficiently catalyzed by the primary amine thiourea catalyst and the desired products were formed in high yields with moderate to excellent enantioselectivities.

A novel type of primary amine thiourea organocatalysts derived from 1,2-diaminocyclohexane and 9-amino (9-deoxy) cinchona alkaloid was developed into asymmetric Michael addition of malonates to enones. A series of cyclic and acyclic enones could react very well with different malonates in the presence of 4 with 0.5-10 mol % catalyst loading affording chiral Michael adducts with excellent yields and ee values.

Lewis base-bronsted base bifunctional catalysis is a novel and practical strategy for the asymmetric michael addition. the addition of malonates to a series of cc,p-unsaturated aldehydes can take place under base-base bifunctional catalytic conditions using 0.5-5 mol% of (s)-2-[diphenyl(trimethyl-silyloxy)methyl]pyrrolidine as catalyst and 5-30 mol% of lithium 4-fluorobenzoate as additive base with up to 99% ee.

We report herein an efficient, general and green method for decarboxylative fluorination of aliphatic carboxylic acids. By using a transition-metal-free, organocatalytic photoredox system, the reaction of various aliphatic carboxylic acids with the Selectfluor reagent afforded the corresponding alkyl fluorides in satisfactory yields under visible light irradiation at room temperature.

A highly enantioselective synthesis of spirocycles and bridged rings has been developed through a formal [4 + 2] cycloaddition reaction between enones and N-sulfonylimines. The unprecedented strategy has been realized utilizing N-sulfonylimine as a novel dienophile through enamine–iminium tautomerism of N-sulfonylimine. In addition, a γ,e-regioselective cycloaddition reaction proceeded by employing methylene chromene species as dienophiles.

Either anti- or syn-configured oxindole derivatives possessing a vicinal quaternary and tertiary stereogenic center are obtained with high enantioselectivities by use of two complementary chiral diamine catalysts and through modifying the substrates.

A tert-leucine-derived chiral diamine efficiently catalyzes the asymmetric Michael addition of nitromethane to five, six-, and seven-membered β-substituted cyclic enones furnishing the corresponding adducts with quaternary stereocenter in excellent enantioselectivities.

The expansion of cross-coupling components in Cu-catalyzed C–X bond forming reactions have received much attention recently. A novel Cu-catalyzed trifluoromethylthiolation of aryl bromides and iodides with the assistance of versatile directing groups such as pyridyl, methyl ester, amide, imine and oxime was reported. CuBr was used as the catalyst, and 1,10-phenanthroline as the ligand. By changing the solvent from acetonitrile to DMF, the coupling process could even take place at room temperature.

Trichloroisocyanuric acid (TCCA) is a cheap, safe and readily available alternative to the commonly used hydrogen peroxide and hypochlorite for the phase-transfer catalytic epoxidation of alpha,beta-enones under non-aqueous conditions. A variety of chalcone derivatives give the corresponding epoxides with quantitative conversion and satisfactory yields in just a few hours under mild conditions. An asymmetric variant of the epoxidation can be carried out in the presence of chiral N-anthracenylmethylcinchonidine bromide catalyst giving 73-93% ees and 76-94% yields.

The expansion of cross-coupling components in Cu-catalyzed C–X bond forming reactions have received much attention recently. A novel Cu-catalyzed trifluoromethylthiolation of aryl bromides and iodides with the assistance of versatile directing groups such as pyridyl, methyl ester, amide, imine and oxime was reported. CuBr was used as the catalyst, and 1,10-phenanthroline as the ligand. By changing the solvent from acetonitrile to DMF, the coupling process could even take place at room temperature.

The enantioselective addition of diarylphosphines to α,β-unsaturated sulfonic esters is developed using the PCP pincer-Pd complex as catalyst.

The title reaction proceeds via a trienamine mechanism and gives rise to the formation of spirocyclic compounds (III) and (V) in good yields and excellent stereoselectivities.

Inexpensive and easily prepared chiral primary diamine is an efficient catalyst for the title reaction under mild conditions.

Aminocatalyzed asymmetric Diels–Alder reaction between 2,4-dienals and rhodanine/hydantoin derivatives via trienamine mechanism has been developed to synthesize various spirocyclic compounds with good yields (up to 98%) and excellent stereoselectivities (up to 99% ee and >19 : 1 dr).

Rhodamine derivatives (I) are applied in cascade reactions for the highly stereoselective construction of title compounds (III) and (V) bearing multiple consecutive chiral centers catalyzed by a simple diamine.

Inexpensive and easily prepared chiral primary diamine is an efficient catalyst for the title reaction under mild conditions.

A diamine-catalyzed asymmetric tandem reaction between α,β-unsaturated ketones and rhodanine derivatives has been developed to synthesize various spirocyclic compounds with high stereoselectivities (up to 99% ee and >20:1 dr). The products obtained contain two pharmaceutically relevant features: the biologically active rhodanine moiety embedded in a spirocyclic unit.

A bulky group was introduced by design into a diamine catalyst, and a series of robust and tunable bulky chiral primary amine catalysts were developed and successfully applied in the direct conjugate addition of substituted rhodanines to α,β-unsaturated ketones. High yields (up to 99%) and excellent diastereoselectivities (up to 99:1 dr) and enantioselectivities (up to 98% ee) were observed.

A bulky group was introduced by design into a diamine catalyst, and a series of robust and tunable bulky chiral primary amine catalysts were developed and successfully applied in the direct conjugate addition of substituted rhodanines to α,β-unsaturated ketones. High yields (up to 99%) and excellent diastereoselectivities (up to 99:1 dr) and enantioselectivities (up to 98% ee) were observed.

A new thiourea-tertiary amine bifunctional catalyst derived from L-tert-leucine was developed and provides excellent stereocontrol in a novel and direct Michael addition of 5H-oxazol-4-ones to α,β-unsaturated ketones with much broad substrate scope. The conjugate addition products with chiral vicinal quaternary and tertiary stereocenters can be easily transformed to structurally interesting compounds or building blocks.

A novel and simple organocatalytic domino Michael—Aldol reaction is reported providing products (III) (21 examples) with three stereocenters in good yields and with excellent diastereo- and enantioselectivities.

The process is highly diastereoselective and produces polycyclic heterocycles in the presence of a bifunctional thiourea catalyst.

The process allows access to highly substituted cyclopropane units, which are formed with complete diastereoselectivity and high enantioselectivity.

In the presence of a Jorgensen—Hayashi catalyst, δ-keto products (III) can be obtained in good regio- and stereoselectivity.

Reaction of lactam (I) with α,β-unsaturated ketones provides Michael adducts with high diastereo- and enantioselectivity.

Highly diastereo- and enantioselective one-pot Michael–Aldol reactions of α,β-unsaturated aldehydes with imidazole derivatives have been developed. The cascade reactions products could be obtained with three stereocenters in high yields and excellent diastereo- and enantioselectivities.