Direct Palladium‐Catalyzed β‐Arylation of Lactams

A direct and catalytic method is reported here for β‐arylation of N‐protected lactams with simple aryl iodides. The transformation is enabled by merging soft enolization of lactams, palladium‐catalyzed desaturation, Ar?X bond activation, and aryl conjugate addition. The reaction is operated under mild reaction conditions, is scalable, and is chemoselective. Application of this method to concise syntheses of pharmaceutically relevant compounds is demonstrated.     

Transition‐Metal‐Free Regioselective Alkylation of Pyridine N‐Oxides Using 1,1‐Diborylalkanes as Alkylating Reagents

Reported herein is an unprecedented base‐promoted deborylative alkylation of pyridine N‐oxides using 1,1‐diborylalkanes as alkyl sources. The reaction proceeds efficiently for a wide range of pyridine N‐oxides and 1,1‐diborylalkanes with excellent regioselectivity. The utility of the developed method is demonstrated by the sequential C?H arylation and methylation of pyridine N‐oxides. The reaction also can be applied for the direct introduction of a methyl group to 9‐O‐methylquinine N‐oxide, thus it can serve as a powerful method for late‐stage functionalization.     

Silver‐Mediated Oxidative Aliphatic CH Trifluoromethylthiolation

The first example of a practical and direct trifluoromethylthiolation reaction of unactivated aliphatic C? H bonds employs a silver‐based reagent. The reaction is operationally simple, scalable, and proceeds under aqueous conditions in air. Furthermore, its broad scope and good functional‐group compatibility were demonstrated by applying this method to the selective trifluoromethylthiolation of natural products and natural‐product derivatives.     

Coordination‐Directed Growth of Transition‐Metal–Crystalline‐Carbon Composites with Controllable Metal Composition

Transition‐metal–carbon (CTM) composites show ample activity in many catalytic reactions. However, control of composition, distribution, and properties is challenging. Now, a straightforward path for the synthesis of transition‐metal nanoparticles engulfed in crystalline carbon is presented with excellent control over the metal composition, amount, ratio, and catalytic properties. This approach uses molten monomers that coordinate metals ions at high temperature. At high temperatures, strong coordination bonds direct the growth of carbon material with homogeneous metals distribution and with negligible losses, owing to the liquid‐like reaction compared to the traditional solid‐state reaction. The strength of the approach is demonstrated by the synthesis of mono, binary, and trinary transition‐metal–crystalline‐carbon composites with tunable and precise elemental composition as well as good electrochemical properties as oxygen evolution reaction electrocatalysts.     

Organocatalytic,Asymmetric Eliminative [4+2] Cycloaddition of Allylidene Malononitriles with Enals: Rapid Entry to Cyclohexadiene‐Embedding Linear and Angular Polycycles

A direct aminocatalytic synthesis has been developed for the chemo‐, regio‐, diastereo‐, and enantioselective construction of densely substituted polycyclic carbaldehydes containing fused cyclohexadiene rings. The chemistry utilizes, for the first time, remotely enolizable π‐extended allylidenemalononitriles as electron‐rich 1,3‐diene precursors in a direct eliminative [4+2] cycloaddition with both aromatic and aliphatic α,β‐unsaturated aldehydes. The generality of the process is demonstrated by approaching 6,6‐, 5,6‐, 7,6‐, 6,6,6‐, and 6,5,6‐fused ring systems, as well as biorelevant steroid‐like 6,6,6,6,5‐ and 6,6,6,5,6‐rings. A stepwise reaction mechanism for the key [4+2] addition is proposed as a domino bis‐vinylogous Michael/Michael/retro‐Michael reaction cascade. The utility of the malononitrile moiety as traceless activating group of the dicyano nucleophilic substrates is demonstrated.     

Silver‐Mediated Oxidative Aliphatic C?H Trifluoromethylthiolation

The first example of a practical and direct trifluoromethylthiolation reaction of unactivated aliphatic C H bonds employs a silver‐based reagent. The reaction is operationally simple, scalable, and proceeds under aqueous conditions in air. Furthermore, its broad scope and good functional‐group compatibility were demonstrated by applying this method to the selective trifluoromethylthiolation of natural products and natural‐product derivatives.     

Organocatalytic,Asymmetric Eliminative [4+2] Cycloaddition of Allylidene Malononitriles with Enals: Rapid Entry to Cyclohexadiene‐Embedding Linear and Angular Polycycles

A direct aminocatalytic synthesis has been developed for the chemo‐, regio‐, diastereo‐, and enantioselective construction of densely substituted polycyclic carbaldehydes containing fused cyclohexadiene rings. The chemistry utilizes, for the first time, remotely enolizable π‐extended allylidenemalononitriles as electron‐rich 1,3‐diene precursors in a direct eliminative [4+2] cycloaddition with both aromatic and aliphatic α,β‐unsaturated aldehydes. The generality of the process is demonstrated by approaching 6,6‐, 5,6‐, 7,6‐, 6,6,6‐, and 6,5,6‐fused ring systems, as well as biorelevant steroid‐like 6,6,6,6,5‐ and 6,6,6,5,6‐rings. A stepwise reaction mechanism for the key [4+2] addition is proposed as a domino bis‐vinylogous Michael/Michael/retro‐Michael reaction cascade. The utility of the malononitrile moiety as traceless activating group of the dicyano nucleophilic substrates is demonstrated.     

Proline–threonine dipeptide as an organocatalyst for the direct asymmetric aldol reaction

A new proline–threonine (H-Pro-Thr-OH) dipeptide has been demonstrated as an efficient organocatalyst for a direct asymmetric aldol reaction. It was found that this new peptide-based catalyst efficiently catalyzed the reaction between an aldehyde and acetone to provide β-hydroxy ketones in good yields with good enantioselectivities.     

Catalytic Enantioselective Quick Route to Aldol‐Tethered 1,6‐ and 1,7‐Enynes from ω‐Unsaturated Aldehydes

An effective asymmetric route to functionalized 1,6‐ and 1,7‐enynes has been developed based on a direct cross‐aldol reaction between ω‐unsaturated aldehydes and propargylic aldehydes (α,β‐ynals) promoted by combined α,α‐dialkylprolinol ether/Brønsted acid catalysis. This synergistic activation strategy is key to accessing the corresponding aldol adducts with high stereoselectivity, both enantio‐ and diastereoselectivity. The aldol reaction also proceeds well with propargylic ketones (α,β‐ynones) thus enabling a stereocontrolled access to the corresponding tertiary alcohols. The utility of these adducts, which are difficult to prepare through standard methodology, is demonstrated by their transformation into trisubstituted bicyclic enones using standard Pauson–Khand conditions.     

Hierarchical fractal‐structured allophanate‐derived network formation in bulk polyurethane synthesis

Polyurethanes are among the most applied and researched polymers worldwide. Nevertheless, polyurethane synthesis is accompanied by a side‐reaction occurring between isocyanate groups and the secondary nitrogen of already formed urethane groups, leading to the formation of crosslinking allophanates. This inevitably requires the development of highly diagnostic direct analytical methods that can be performed in the solid state of the polymer. The present research focused on the direct investigation and diagnostic determination of the chemical structure formation in bulk polyurethane synthesis, using a combination of Fourier transform infrared and solid‐state ¹³C nuclear magnetic resonance analysis. Polyurethane syntheses were performed in bulk and designed as to obtain significantly strong diagnostic analytical measurements signals for the accurate identification of each of the investigated chemical structures. The present research results led to the conclusive analytical identification of allophanate formation during polyurethane synthesis. In addition, the occurrence of a new reaction mechanism was discovered in the present research. It was demonstrated in the present research that this newly described reaction occurs via the further reaction of the allophanate secondary nitrogen with an isocyanate group, the reaction creating a tertiary nitrogen and an additional reactive secondary nitrogen, and so on, in a consecutive step progression, leading to the formation of a 3‐dimensional hierarchical fractal‐like crosslinked polymeric structure. Solid‐state ¹³C nuclear magnetic resonance analysis results were highly consistent with the Fourier transform infrared results. The discovery of this newly described reaction can facilitate the optimization of industrial processes and potentially opens a new door to the development of a vast variety of biomedical and nanotechnology applications.     

Enantioselective Synthesis of 3a‐Amino‐Pyrroloindolines by Copper‐Catalyzed Direct Asymmetric Dearomative Amination of Tryptamines

A direct asymmetric dearomative amination of tryptamines with O‐(2,4‐dinitrophenyl)hydroxylamine (DPH) was achieved using CuBr‐bisoxazoline complex as a catalyst, affording 3a‐amino‐pyrroloindolines in good to excellent enantioselectivity under mild reaction conditions. Furthermore, the synthetic value of this method was demonstrated in the total synthesis of (?)‐psychotriasine in a highly concise manner.     

Temperature‐dependent feature sensitivity analysis for combustion modeling

Sensitivity analysis is one of the most widely used tools in kinetic modeling. Typically, it is performed by perturbing the A‐factors of the individual reaction rate coefficients and monitoring the effect of these perturbations on the observables of interest. However, the sensitivity coefficients obtained in this manner do not contain direct information on possible temperature‐dependent effects. Yet, in many combustion processes, especially in premixed flames, the system undergoes substantial temperature changes, and the relative importance of individual reaction rates may vary significantly within the flame. An extension of conventional sensitivity analysis developed in the present work provides the means of identifying the temperatures at which individual reaction rate coefficients are most important as a function of input parameters and specific experimental conditions. The obtained information is demonstrated to be of critical relevance in optimizing complex reaction schemes against multiple experimental targets. Applications of the presented approach are not limited to sensitivities with respect to reaction rate coefficients; the method can be used for any temperature‐dependent property of interest (such as binary diffusion coefficients). This application is also demonstrated in this paper. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 282–295, 2005     

Palladium‐Catalyzed,tert‐Butyllithium‐Mediated Dimerization of Aryl Halides and Its Application in the Atropselective Total Synthesis of Mastigophorene A

A palladium‐catalyzed direct synthesis of symmetric biaryl compounds from aryl halides in the presence of tBuLi is described. In situ lithium–halogen exchange generates the corresponding aryl lithium reagent, which undergoes a homocoupling reaction with a second molecule of the aryl halide in the presence of the palladium catalyst (1 mol %). The reaction takes place at room temperature, is fast (1 h), and affords the corresponding biaryl compounds in good to excellent yields. The application of the method is demonstrated in an efficient asymmetric total synthesis of mastigophorene A. The chiral biaryl axis is constructed with an atropselectivity of 9:1 owing to catalyst‐induced remote point‐to‐axial chirality transfer.     

Palladium‐Catalyzed,tert‐Butyllithium‐Mediated Dimerization of Aryl Halides and Its Application in the Atropselective Total Synthesis of Mastigophorene A

A palladium‐catalyzed direct synthesis of symmetric biaryl compounds from aryl halides in the presence of tBuLi is described. In situ lithium–halogen exchange generates the corresponding aryl lithium reagent, which undergoes a homocoupling reaction with a second molecule of the aryl halide in the presence of the palladium catalyst (1 mol %). The reaction takes place at room temperature, is fast (1 h), and affords the corresponding biaryl compounds in good to excellent yields. The application of the method is demonstrated in an efficient asymmetric total synthesis of mastigophorene A. The chiral biaryl axis is constructed with an atropselectivity of 9:1 owing to catalyst‐induced remote point‐to‐axial chirality transfer.     

Synthesis of C3‐Methyl‐Substituted Pyrroloindolines and Furoindolines via Cascade Dearomatization of Indole Derivatives with Methyl Iodide

A highly efficient method for constructing C3‐methyl‐substituted pyrroloindolines and furoindolines via cascade dearomatization reaction of indole derivatives with methyl iodide was developed. This protocol offers a direct approach to a wide range of C3 methyl substituted pyrroloindolines under mild conditions. The utility of this method was further demonstrated in the concise synthesis of (±)‐esermethol.     

Catalytic asymmetric direct alpha-amination reactions of 2-keto esters: a simple synthetic approach to optically active syn-beta-amino-alpha-hydroxy esters

The catalytic enantioselective direct alpha-amination reaction of 2-keto esters with easily available azo dicarboxylates as the nitrogen source and chiral bisoxazoline-copper(II) complexes as the catalyst is presented. The reactions proceed with excellent enantioselectivities and high yields. The scope of the reaction is demonstrated by the direct amination of a series of 2-keto esters having different substituent patterns. The reaction provides an easy catalytic route to optically active syn-beta-amino-alpha-hydroxy esters, as demonstrated for the synthesis of masked syn-beta-amino-alpha-hydroxy esters (as oxazolidinones) and N-Boc-syn-beta-amino-alpha-hydroxy esters. On the basis of the absolute configuration of the products a tentative model for the transition state is suggested.     

Copper‐Promoted Sandmeyer Difluoromethylthiolation of Aryl and Heteroaryl Diazonium Salts

An efficient copper‐promoted difluoromethylthiolation of aryl and heteroaryl diazonium salts is described. The reaction is conducted under mild reaction conditions and various functional groups were compatible. In addition, reactions of heteroaryl diazonium salts such as pyridyl, quinolinyl, benzothiazolyl, thiophenyl, carbazolyl, and pyrazolyl diazonium salts occurred smoothly to afford the medicinally important difluoromethylthiolated heteroarenes. Furthermore, a more practical one‐pot direct diazotization and difluoromethylthiolation protocol was developed, and it converts the aniline derivatives into difluoromethylthiolated arenes. The utility of the method is demonstrated by difluoromethylthiolation of a number of natural products and drug molecules.     

Solar‐Energy‐Driven Photoelectrochemical Biosensing Using TiO2 Nanowires

Photoelectrochemical sensing represents a unique means for chemical and biological detection, with foci of optimizing semiconductor composition and electronic structures, surface functionalization layers, and chemical detection methods. Here, we have briefly discussed our recent developments of TiO₂ nanowire‐based photoelectrochemical sensing, with particular emphasis on three main detection mechanisms and corresponding examples. We have also demonstrated the use of the photoelectrochemical sensing of real‐time molecular reaction kinetic measurements, as well as direct interfacing of living cells and probing of cellular functions.     

Palladium‐Catalyzed Enantioselective Thiocarbonylation of Styrenes

A highly enantioselective thiocarbonylation of styrenes with CO and thiols has been achieved by Pd catalysis, providing highly enantioenriched thioesters in good to excellent yields. Key to the successful execution of this reaction is the use of a chiral sulfoxide‐(P‐dialkyl)‐phosphine (SOP) ligands. This thiocarbonylation proceeds smoothly under mild reaction conditions (1 atm CO and 0 °C) and displays broad substrate scope. Also demonstrated is that this transformation can be conducted using surrogates of CO, greatly increasing the safety aspects of running the reaction. The generality and utility of the method is manifested by its application to the synthetic transformations of thioester products and the direct acylation of cysteine‐containing dipeptides. A primary mechanism was investigated and a plausible catalytic cycle was proposed.     

Effect of water addition on the cure kinetics of an epoxy‐amine thermoset

In this study, the effect of water addition on cure kinetics in an epoxy‐amine thermoset was investigated. Near FTIR spectra demonstrated that a small amount of water addition significantly accelerated the cure reaction in terms of epoxide conversion, with water acting as a catalyst for the reaction. Use of a modified mechanistic model allowed direct comparison of the effect of hydroxyl groups generated from water addition to those generated from the polymer chain. The comparison of those kinetic parameters shows that the two effects are very close, in which difference in the logarithmic value of the reaction constant is less than one order of magnitude over all the reaction conditions. The kinetic study also confirmed a strong negative substitution effect for this system. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011