Palladium-catalyzed cascade allylation/carbopalladation/cross coupling: a novel three-component reaction for the synthesis of 3,3-disubstituted-2,3-dihydrobenzofurans

A novel one-pot palladium-catalyzed cascade between 2-iodophenol, methyl bromomethylacrylate and an arylboronic acid provides an efficient access to heterocycles possessing the 3,3-disubstituted-2,3-dihydrobenzofuran skeleton via allylation/carbopalladation/Suzuki cross-coupling.     

Highly efficient three-component synthesis of protected homoallylic amines by bismuth triflate-catalyzed allylation of aldimines

Bismuth triflate catalyzes the allylation of a variety of in situ generated protected aldimines using aldehydes, primary carbamates, and allyltrimethylsilane in a three-component reaction. The reaction proceeds rapidly and affords the corresponding protected homoallylic amine in good yield (up to 86%). Scope and limitations of the aldehyde and carbamate components are reported.     

Selective formation of 2-imidazolines and 2-substituted oxazoles by using a three-component reaction

Selective formation of 2H‐2‐imidazolines and 2‐substituted oxazoles by using a multicomponent reaction of amines, either aldehydes or ketones, and α‐acidic isocyano amides or esters is described. By selecting the appropriate solvent, Ag^I or Cu^I catalyst, or by employing a weak Brønsted acid, the product formation can be fully controlled and directed quantitatively to the desired heterocyclic scaffold. The described experimental procedures not only significantly increase the scope of compatible inputs for this complexity‐generating three‐component reaction, but also allow for considerable chemical diversity: At least four diversity points in two distinct scaffolds can be exploited in this way.     

Synthesis of homoallylic amines and acylhydrazides by tin powder‐promoted multicomponent one‐pot allylation reactions

An efficient process for the synthesis of homoallylic amines and N′‐homoallylic hydrazides is developed from the one‐pot reaction of carbonyl compounds, amines or N‐acylhydrazines, allyllic bromide and tin powder using water as solvent. N‐Acylhydrazines are found to be more reactive than amines in these processes. They can react not only with aldehydes but also with ketones to give the corresponding N′‐homoallylic hydrazides. Copyright © 2016 John Wiley & Sons, Ltd.     

Asymmetric three-component Strecker reactions catalyzed by trans-4-hydroxy-L-proline-derived N,N'-dioxides

Novel trans-4-hydroxy-L-proline-derived N,N'-dioxides have been developed and used as efficient organocatalysts for the one-pot three-component Strecker reaction with an aldehyde, (1,1-diphenyl)methylamine, and TMSCN. Both aromatic and aliphatic aldehydes were found to be suitable substrates. The corresponding alpha-amino nitriles were obtained in high yields with up to 95 % ee (ee=enantiomeric excess) under mild conditions. Optically pure products could be obtained after a single recrystallization. The catalyst can be easily prepared from trans-4-hydroxy-L-proline and a diamine in three steps. Based on the experimental results and the observed absolute configurations of the products, a possible transition state has been proposed to explain the origin of the asymmetric induction.     

Excess volumes of quinoline with nitroalkanes: Interpretation by the Prigogine-Flory-Patterson theory

Excess volumes of V ^E of binary liquid mixtures of quinoline with each of the nitroalkanes have been measured at 30°C as a function of composition using a continuous dilution dilatometer. The excess volumes are negative over the whole mole-fraction range for all the mixtures except quinoline + nitromethane, which exhibits positive V ^E over the whole range. V ^E results have been analyzed in the light of the Prigogine-Flory-Patterson theory, which divides V ^E into three contributions. The agreement between experimental and theoretical values is reasonably good.     

An Efficient Amide‐Aldehyde‐Alkene Condensation: Synthesis for the N‐Allyl Amides

The allylamine skeleton represents a significant class of biologically active nitrogen compounds that are found in various natural products and drugs with well‐recognized pharmacological properties. In this personal account, we will briefly discuss the synthesis of allylamine skeletons. We will focus on showing a general protocol for Lewis acid‐catalyzed N‐allylation of electron‐poor N‐heterocyclic amides and sulfonamide via an amide‐aldehyde‐alkene condensation reaction. The substrate scope with respect to N‐heterocyclic amides, aldehydes, and alkenes will be discussed. This method is also capable of preparing the Naftifine motif from N‐methyl‐1‐naphthamide or methyl (naphthalene‐1‐ylmethyl)carbamate, with paraformaldehyde and styrene in a one‐pot manner.     

A substrate-based folding process incorporating chemodifferentiating ABB' three-component reactions of terminal alkynoates and 1,2-dicarbonyl compounds: a skeletal-diversity-oriented synthetic manifold

A novel three-component reaction (3CR)-based folding process that is able to generate complexity and skeletal diversity is described. The process utilizes chemodifferentiating organocatalyzed ABB' 3CRs of a terminal conjugated alkynoate (building block) with alpha-dicarbonyl compounds (diversity-generating blocks) to generate an array of different molecular topologies (gamma-lactones, linear propargylic enol ethers, or 1,3-dioxolane rings). Amides and esters behave as efficient reactivity-encoding elements (sigma) of the attached keto functionality. Three chemical properties govern the chemical outcome of this folding process: acidity, nucleophilicity (of the catalyst), and carbonyl electrophilicity. Overall, this substrate-based folding process generates three different molecular architectures from the same modular functionalities (ketones) and under the same reaction conditions (methyl propiolate and tertiary amine). In addition, and very importantly for combinatorial applications, all of the products share a common reactive functionality that allows them to be collective substrates for a subsequent diversity-generating process.     

Fe‐Catalyzed Multicomponent Reactions: The Regioselective Alkoxy Allylation of Activated Olefins and its Application in Sequential Fe Catalysis

We present herein a versatile and broadly applicable Fe‐catalyzed regioselective alkoxy allylation of activated double bonds. Substituted allylic carbonates are converted into the corresponding σ‐enyl Fe complexes by reaction with Bu₄N[Fe(CO)₃(NO)] (TBAFe) at 30 °C. The liberated alkoxide adds to an activated double bond with the generation of a C‐nucleophile, which is trapped by the σ‐enyl Fe complex in a regioselective manner. Alternatively, the alkoxide acts as a base in deprotonating an external pronucleophile, which undergoes Michael addition. The method is characterized by a broad functional group tolerance, mild reaction conditions, low catalyst loadings, and high regioselectivities in favor of the ipso‐substitution product.