Enantioselective hydrophosphonylation of N-Boc imines using chiral guanidine-thiourea catalysts.

The enantioselective hydrophosphonylation of N-Boc imines was investigated using a new family of pseudo-symmetric guanidine-thiourea catalysts, providing α-amino phosphonates in moderate to high yields with good enantioselectivity. The catalyst was heterogenized by polymerization with styrene and the resulting catalyst was applied to reactions under continuous-flow conditions.

One-Pot Synthesis of α,ß-Unsaturated γ-Lactones and Lactams via a Sequential trans-Hydroalumination and Catalytic Carboxylation of Propargyl Alcohols and Amines with Carbon Dioxide.

A one-pot, sequential process that combines a trans-selective hydroalumination of propargyl alcohols and amines with a copper- or silver-catalyzed carboxylation reaction using carbon dioxide, followed by an acid-mediated intramolecular condensation step, led to the formation of a wide range of α,ß-unsaturated γ-butyrolactones and lactams.

Reworking Organic Synthesis for the Modern Age: Synthetic Strategies Based on Continuous-Flow Addition and Condensation Reactions with Heterogeneous Catalysts.

While organic synthesis carried out in most laboratories uses batch methods, there is growing interest in modernizing fine chemical synthesis through continuous-flow processes. As a synthetic method, flow processes have several advantages over batch systems in terms of environmental compatibility, efficiency, and safety, and recent advances have allowed for the synthesis of several complex molecules, including active pharmaceutical ingredients (APIs). Nevertheless, due to several reasons related to the difficulties arising from byproduct formation during the flow process, such as lower yields, poor selectivities, clogging of columns due to poor solubility, catalyst poisoning, etc., successful examples of continuous-flow synthesis of complex organic molecules are still limited. In order to solve this bottleneck, the development of selective and atom-economical continuous-flow organic transformations are needed. This perspective highlights examples of atom-economical addition and condensation reactions with heterogeneous catalysts under continuous-flow conditions and their applications for the synthesis of complex organic molecules such as natural products and APIs. In order to realize new continuous-flow methodologies, based on addition and condensation reactions, in place of substitution reactions, the development of novel reactions and heterogeneous catalysts is required.

A Nickel-Diamine/Mesoporous Silica Composite as a Heterogeneous Chiral Catalyst for Asymmetric 1,4-Addition Reactions.

A chiral composite material, derived from the deposition of a chiral nickel-diamine complex via wet impregnation to MCM-41, was shown to be an efficient heterogeneous catalyst for asymmetric 1,4-addition reactions of 1,3-dicarbonyl compounds with nitroalkenes, and of nitromethane with alkylidenemalonates. It was discovered that MCM-41 enhanced the reactivity and improved the stability of the chiral nickel complex that resides within the mesoporous material.

Efficient Synthesis of α-Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of gem-Difluoroalkenes.

A facile synthetic procedure for the preparation of α-trifluoromethyl carboxylic acids and esters was achieved through multicomponent coupling reactions between gem-difluoroalkenes, cesium fluoride, and carbon dioxide. The products were generated in moderate to excellent yields, and the synthetic utility of this method was demonstrated through the preparation of trifluoromethylated versions of popular nonsteroidal anti-inflammatory drugs (NSAIDs).

Catalytic enantioselective aldol reactions.

Recent developments in catalytic asymmetric aldol reactions have been summarized. Enantioselective aldol reactions are important methods to synthesize ß-hydroxy carbonyl compounds in optical pure form, and as such, numerous successful chiral catalysts were designed and applied for asymmetric aldol reactions. This review article is organized under the categories of: (1) catalytic enantioselective aldol reactions of preformed enolates, (2) catalytic enantioselective direct-type aldol reactions using chiral metal catalysts, (3) catalytic enantioselective direct-type aldol reactions using organocatalysts, (4) catalytic enantioselective aldol reactions in aqueous media. Examples of the aldol reactions that employ simple carbonyl compounds will be also the focus of this review.

Integration of aerobic oxidation and intramolecular asymmetric aza-Friedel-Crafts reactions with a chiral bifunctional heterogeneous catalyst.

A new class of chiral bifunctional heterogeneous materials composed of Au/Pd nanoparticles and chiral phosphoric acids as active orthogonal catalysts was prepared by utilizing a facile pseudo-suspension co-polymerization method. It was found that this heterogeneous catalyst was capable of facilitating the sequential aerobic oxidation-asymmetric intramolecular aza-Friedel-Crafts reaction between benzyl alcohols and N-aminoethylpyrroles. Moreover, the designed chiral heterogeneous catalyst could be recovered and reused several times without significant loss of activity or enantioselectivity.

Visible Light-Mediated Ullmann-Type C-N Coupling Reactions of Carbazole Derivatives and Aryl Iodides.

The combined use of an iridium-based photocatalyst and a copper salt under blue light emitting diode irradiation enables the Ullmann-type C-N cross-coupling reaction between carbazole derivatives and aryl iodides to proceed under mild conditions.

Effective Formylation of Amines with Carbon Dioxide and Diphenylsilane Catalyzed by Chelating bis(tzNHC) Rhodium Complexes.

The reductive formylation of amines using CO2 and hydrosilanes is an attractive method for incorporating CO2 into valuable organic compounds. However, previous systems required either high catalyst loadings or high temperatures to achieve high efficiency, and the substrate scope was mostly limited to simple amines. To address these problems, a series of alkyl bridged chelating bis(NHC) rhodium complexes (NHC=N-heterocyclic carbene) have been synthesized and applied to the reductive formylation of amines using CO2 and Ph2SiH2. A rhodium-based bis(tzNHC) complex (tz=1,2,3-triazol-5-ylidene) was identified to be highly effective at a low catalyst loading and ambient temperature, and a wide substrate scope, including amines with reducible functional groups, were compatible.

Visible-light-mediated chan-lam coupling reactions of aryl boronic acids and aniline derivatives.

The copper(II)-catalyzed aerobic oxidative coupling reaction between aryl boronic acids and aniline derivatives was found to be improved significantly under visible-light-mediated photoredox catalysis. The substrate scope of this oxidative Chan-Lam reaction was thus expanded to include electron-deficient aryl boronic acids as viable starting materials.

Synthesis of isocoumarins through three-component couplings of arynes, terminal alkynes, and carbon dioxide catalyzed by an NHC-copper complex.

A copper-catalyzed multicomponent coupling reaction between in situ generated ortho-arynes, terminal alkynes, and carbon dioxide was developed to access isocoumarins in moderate to good yields. The key to this CO2-incorporating reaction was the use of a versatile N-heterocyclic carbene/copper complex that was able to catalyze multiple transformations within the three-component reaction.

Sulfuryl chloride as an efficient initiator for the metal-free aerobic cross-dehydrogenative coupling reaction of tertiary amines.

A metal-free cross-dehydrogenative (CDC) reaction of tertiary amines was developed using a catalytic amount of sulfuryl chloride (SO2Cl2) under mild aerobic conditions. On the basis of the nature of SO2Cl2, it was assumed that the reagent acts as a radical initiator to induce the metal-free CDC reaction via a radical-initiated autoxidation mechanism.

A heterogeneous layered bifunctional catalyst for the integration of aerobic oxidation and asymmetric C-C bond formation.

The design and synthesis of a heterogeneous bifunctional chiral catalyst for the sequential aerobic oxidation-asymmetric Michael reactions between primary allylic alcohols and dibenzyl malonate are described. Interestingly, we found that layering bimetallic nanoparticles over the organocatalyst, within the chiral composite material, is crucial for catalytic activity.

Aerobic oxidation of a tertiary aliphatic amine under visible-light photocatalysis: facile synthesis of methylene-bridged bis-1,3-dicarbonyl compounds.

Lights, camera, action! An efficient protocol for the formation of methylene-bridged bis-1,3-dicarbonyl compounds has been developed through an aerobic photocatalytic oxidative coupling reaction between 1,3-dicarbonyl compounds and a tertiary aliphatic amine.

Base-mediated carboxylation of unprotected indole derivatives with carbon dioxide.

A simple and straightforward method for the preparation of indole-3-carboxylic acids was discovered through the direct carboxylation of indoles with atmospheric pressure of carbon dioxide (CO(2)) under basic conditions. The key for the reaction was found to be the use of a large excess of LiO(t)Bu as a base to suppress the undesired decarboxylation side reaction.

Discovery of a metalloenzyme-like cooperative catalytic system of metal nanoclusters and catechol derivatives for the aerobic oxidation of amines.

We have discovered a new class of cooperative catalytic system, consisting of heterogeneous polymer-immobilized bimetallic Pt/Ir alloyed nanoclusters (NCs) and 4-tert-butylcatechol, for the aerobic oxidation of amines to imines under ambient conditions. After optimization, the desired imines were obtained in good to excellent yields with broad substrate scope. The reaction rate was determined to be first-order with respect to the substrate and catechol and zero-order for the alloyed Pt/Ir NC catalyst. Control studies revealed that both the heterogeneous NC catalyst and 4-tert-butylcatechol are essential and act cooperatively to facilitate the aerobic oxidation under mild conditions.

Polymer-incarcerated gold-palladium nanoclusters with boron on carbon: a mild and efficient catalyst for the sequential aerobic oxidation-Michael addition of 1,3-dicarbonyl compounds to allylic alcohols.

We have developed a polymer-incarcerated bimetallic Au-Pd nanocluster and boron as a catalyst for the sequential oxidation-addition reaction of 1,3-dicarbonyl compounds with allylic alcohols. The desired tandem reaction products were obtained in good to excellent yields under mild conditions with broad substrate scope. In the course of our studies, we discovered that the excess reducing agent, sodium borohydride, reacts with the polymer backbone to generate an immobilized tetravalent boron catalyst for the Michael reaction. In addition, we found bimetallic Au-Pd nanoclusters to be particularly effective for the aerobic oxidation of allylic alcohols under base- and water-free conditions. The ability to conduct the reaction under relatively neutral and anhydrous conditions proved to be key in maintaining good catalyst activity during recovery and reuse of the catalyst. Structural characterization (STEM, EDS, SEM, and N(2) absorption/desorption isotherm) of the newly prepared PI/CB-Au/Pd/B was performed and compared to PI/CB-Au/Pd. We found that while boron was important for the Michael addition reaction, it was found to alter the structural profile of the polymer-carbon black composite material to negatively affect the allylic oxidation reaction.

Propargyl amine synthesis catalysed by gold and copper thin films by using microwave-assisted continuous-flow organic synthesis (MACOS).

An effective multi-component reaction (MCR) protocol has been developed for the construction of propargyl amines from aldehydes, amines and terminal alkynes by using microwave-assisted continuous-flow organic synthesis (MACOS). The process is catalysed by thin films of either copper or gold that achieve temperatures in excess of 900 degrees C when irradiated with low levels of microwave power. The process works equally well for premixed solutions of the three starting materials, or as three separate streams, which improves the combinatorial efficiency of the method. The process tolerates a wide variety of functional groups and heterocycles, and conversion over these diverse substrates ranges from 70-90 %.

Cross-dehydrogenative coupling reactions of sp3-hybridized C-H bonds.

New methodologies in cross-coupling reaction using C-H bonds as substrates is of great interest due to the challenges associated with C-H bond activation and the potential to streamline synthesis by the elimination of preactivation of coupling reagents. In this chapter, recent developments in oxidative cross-coupling reactions will be presented with the focus on the functionalization of sp3 C-H bonds with other C-H bonds.

Low-valent indium as a catalyst for the allylation of ketones and N-acylhydrazones.

Indium summer: The use of low-valent indium species in organic chemistry was, until quite recently, underdeveloped. Then came reports of indium(I) halides serving as excellent catalysts for the allylation of ketones and N-acylhydrazones with pinacol allylboronates, and more recently of indium(0) being used as a catalyst for the allylation of ketones in water.