A Smiles rearrangement is the key step in efficient coupling of primary amines with isocyanides, carbonyl compounds, and electron-deficient substituted phenols to form N-aryl (see picture). The presence a nitro or ester group on resulting adduct allows applications heterocyclic synthesis. Since pioneering work Passerini Ugi, use isocyanides has been strongly associated success achieved by multicomponent reactions (MCRs) creation molecular diversity.1 high efficiency MCRs lies their ability...

The α-arylation of enolizable aryl ketones can be carried out with halides under transition-metal-free conditions using KOtBu in DMF. α-aryl thus obtained used for step- and cost-economic syntheses fused heterocycles Tamoxifen. Mechanistic studies demonstrate the synergetic role base solvent initiation radical process.

The Ugi reaction is one of the most famous multicomponent couplings, and its efficiency still explained by original mechanism suggested in 60s. This article aims to present a thorough theoretical study this reaction. It describes how imine activated new stereogenic center formed. Our calculations strongly suggest alternatives some commonly accepted features, such as reversibility intermediate steps, temper nature driving force

The mechanism of boron-to-nickel transmetalation, the key step nickel-catalyzed Suzuki-Miyaura (S-M) coupling, was examined both experimentally and theoretically. Dinuclear μ-hydroxo-bridged complexes formed by reaction trans-[ArNi(PR3)2X] with hydroxide are not directly involved in but they rather act as a resting state for catalyst. base/boronic acid ratio is crucial parameter, it modulates extent formation these dinuclear species thus tunes catalytic activity. These findings explain some...

Synthetic yield prediction using machine learning is intensively studied. Previous work has focused on two categories of data sets: high-throughput experimentation data, as an ideal case study, and sets extracted from proprietary databases, which are known to have a strong reporting bias toward high yields. However, predicting yields published reaction remains elusive. To fill the gap, we built set nickel-catalyzed cross-couplings organic publications, including scope optimization...

The use of Smiles rearrangement in Ugi- and Passerini-type couplings with electron-deficient phenols allows very straightforward multicomponent formation O-aryl- N-arylamides. Best yields were observed the highly activated o- p-nitrophenols, salicylic derivatives giving adducts lower yields. scope these new reactions is further increased by successful heterocyclic such as hydroxypyridines hydroxypyrimidines.

Copper-catalyzed olefinic difluoroacetylation of enamides via direct C-H bond functionalization using BrCF2CO2Et is reported for the first time. It constitutes an efficient radical-free method regioselective synthesis β-difluoroester substituted which exhibits broad substrate scope, and thus demonstrates its potent application in a late stage fluorination strategy.

Abstract The Ugi–Smiles and Passerini–Smiles couplings are extensions of Ugi Passerini reactions involving the use acidic phenols in place traditional carboxylic acid partners. A Smiles rearrangement is each case responsible for final N ‐aryl carboxamide formation. All available data on mechanisms scope these presented. To demonstrate interest couplings, have been further applied to preparation various fused heterocyclic systems. These “post‐condensation” studies also covered this review.

Core–shell Au NPs@MOF-808 architecture has been synthesized using sustainable conditions. NPs capping agent removal optimized to boost the catalytic efficiency of composite material.

The oxidative addition (OA) of organic electrophiles to Pd(0) is a fundamental step in organopalladium chemistry and plays key role palladium-catalyzed cross-coupling reactions. This perspective summarizes selected mechanistic studies the Pd(0)-to-Pd(II) OA process involving halides pseudohalides with focus on systems relevant catalytic results are organized according nature supporting ligands, extracting general trends, describing most examples. formation active species from precatalysts...

Mumm's the word: The title reaction can be performed by addition of isocyanides to benzenediazonium salts in presence sodium or potassium carboxylates. involves nitrilium intermediates which may trapped water carboxylic acids form amides and imides, respectively, after Mumm rearrangement. As a service our authors readers, this journal provides supporting information supplied authors. Such materials are peer reviewed re-organized for online delivery, but not copy-edited typeset. Technical...

Experimental and theoretical mechanistic studies on the Cu(OTf)2-catalyzed hydroamination reaction of terminal allenes with secondary amines reveal that in situ generated cationic Cu(I) is catalytically active species explain observed regio- stereoselectivity for unbranched E product. Insight into structure relevant transition states allowed generalization this methodology to allenamides N-allenylcarbamates under unprecedentedly mild functional-group-tolerant conditions. Chelation effects by...

We report the challenging direct carbamoylation or cyanation of benzylic C(sp3)–H bonds with an isocyanide via electrochemical process giving rise to structures that are encountered in several biologically relevant compounds and drugs. This transformation proceeds under mild conditions without need for any external oxidant avoids necessity start from a prefunctionalized substrate deployment cation pool method. The anodic oxidation position subsequent addition lead formation C–C bond...

The integration of machine learning (ML) into chemistry offers transformative potential in the design molecules. However, focus has often been on creating highly efficient predictive models, sometimes at expense interpretability. We leverage explainable AI techniques to explore boron-based Lewis acids, which play a pivotal role organic reactions. Using Fluoride Ion Affinity as proxy for acidity, we developed interpretable ML models based chemically meaningful descriptors, including ab initio...

We report a photoredox-catalyzed pseudo-four-component process for the alkylative amidination of styrenes using isocya-nides and redox-active esters (RAEs). This redox-neutral radical-polar crossover reaction shows broad functional group tol-erance. The RAE serves as both radical nucleophile source, with initially released phthalimide anion reintegrated into final product. resulting amidines can be readily derivatized amides, tetrazoles, nitriles, or aldehydes, en-hancing synthetic utility...

We report a photoredox-catalyzed pseudo-four-component process for the alkylative amidination of styrenes using isocyanides and redox-active esters (RAEs). This redox-neutral radical-polar crossover reaction shows broad functional group tolerance. The RAE...

Addition of dialkylphosphites to aromatic aldehydes (Pudovik reaction) by treatment with a base results in two different possible reaction pathways depending on the solvent used. Apolar solvents give normal Pudovik adduct, whereas use DBU polar allows formation phosphate ester via phospha-Brook rearrangement intermediate hydroxyphosphonate.

New heterocyclic scaffolds can be easily prepared by the coupling of heteroaromatic phenols (pyridines, pyrimidines) with carbonyl compounds, amines, and isocyanides. This transformation related to Ugi reaction probably involves a Smiles rearrangement. The scope this methodology is further extended successful use thiols form highly functionalized thioamides.

The three-component addition of isocyanides to phenol derivatives and aldehydes proceeds easily in methanol form O-arylated compounds a new Passerini-type reaction. key step the conversion lies an irreversible Smiles rearrangement intermediate phenoxyimidate adducts. It represents first use Passerini

The use of ortho-iodonitrophenol in Ugi-Smiles reaction coupled with Heck cyclization gives new access to indole scaffolds. sequence can be performed a one-pot if the residual isocyanide is neutralized prior addition palladium catalyst.

Oxidative cleavage and cyclization cascades of N-aryl peptides have been achieved under palladium catalysis with air as the sole stoichiometric oxidant.