Electron-deficient Alkenes Research Articles

Sequential dual-curing of electron-deficient olefins and alcohols relying on oxa-Michael addition and anionic polymerization

Polymer networks were obtained by anionic copolymerization of diacrylates and sub-stoichiometric amounts of diols using Lewis base catalysis.

2 + 2 Trapping of Acyloxy-1,2-cyclohexadienes with Styrenes and Electron-Deficient Olefins.

Oxygenated-1,2-cyclohexadienes and their unsubstituted counterpart can be generated under mild conditions by fluoride-induced desilylation and undergo intermolecular [2 + 2]-cycloaddition reactions with a variety of alkene traps to afford bicyclo[4.2.0]octenes. Both styrenes and electron-deficient olefins react in good conversion and with complete regioselectivity in favor of cyclobutane formation at the unsubstituted C2/C3 carbons of the C1-substituted cyclic allenes. Diastereoselectivities are modest (1.1-5.7:1) with a preference for the exo-isomer.

Photocatalytic Deuterium Atom Transfer Deuteration of Electron-Deficient Alkenes with High Functional Group Tolerance.

Due to its mild reaction conditions and unique chemoselectivity, hydrogen atom transfer (HAT) hydrogenation represents an indispensable method for the synthesis of complex molecules. Its analog using deuterium, deuterium atom transfer (DAT) deuteration, is expected to enable access to complex deuterium-labeled compounds. However, DAT deuteration has been scarcely studied for synthetic purposes, and a method that possesses the favorable characteristics of HAT hydrogenations has remained elusive. Herein, we report a protocol for the photocatalytic DAT deuteration of electron-deficient alkenes. In contrast to the previous DAT deuteration, this method tolerates a variety of synthetically useful functional groups including haloarenes. The late-stage deuteration also allows access to deuterated amino acids as well as donepezil-d2 . Thus, this work demonstrates the potential of DAT chemistry to become the alternative method of choice for preparing deuterium-containing molecules.

Visible-Light-Promoted Catalyst-Free Oxyarylation and Hydroarylation of Alkenes with Carbon Dioxide Radical Anion.

Visible-light-mediated oxyarylation and hydroarylation of alkenes with aryl halides using formate salts as the reductant and hydrogen source under ambient conditions were developed. These protocols represent rare catalyst-free examples of the realization of such transformations. Using styrenes as substrates, oxyarylation could occur smoothly. Whereas, hydroarylation proceeds employing electron deficient alkenes. Moreover, dehalogenation proceeds successfully in the absence of alkenes. We expected that this method could provide a valuable strategy for the functionalization of aryl halides.

C-H Diselenation and Monoselenation of Electron-Deficient Alkenes via Radical Coupling at Room Temperature.

A new, simple, and metal-free route for the diselenation of maleimides has been first developed employing (bis(trifluoroacetoxy)iodo)benzene (PIFA) at room temperature. The present method is compatible with different functional groups, and various diselenyl maleimides were obtained in moderate to excellent yields. Moreover, this protocol further highlights the unique practical application for the functionalization of biologically relevant molecules and amino acid derivatives. Preliminary mechanism studies suggest that radicals may be involved in this novel transformation. Additionally, this protocol is also applicable for the monoselenation of maleimides by switching the reaction conditions and selenation of other electron-deficient alkenes.

Rhodium(III)-Catalyzed Anti-Markovnikov Hydroamidation of Unactivated Alkenes Using Dioxazolones as Amidating Reagents.

The amide is one of the most prevalent functional groups in all of pharmaceuticals, and for this reason, reactions that introduce the amide moiety are of particular value. Intermolecular hydroamidation of alkenes remains an underexplored method for the synthesis of amide-containing compounds. The majority of hydroamidation procedures exhibit Markovnikov regioselectivity, while current methods for anti-Markovnikov hydroamidation are somewhat limited to activated alkene substrates or radical processes. Herein, we report a general method for the intermolecular anti-Markovnikov hydroamidation of unactivated alkenes under mild conditions, utilizing Rh(III) catalysis in conjunction with dioxazolone amidating reagents and isopropanol as an environmentally friendly hydride source. The reaction tolerates a wide range of functional groups and efficiently converts electron-deficient alkenes, styrenes, and 1,1-disubstituted alkenes, in addition to unactivated alkenes, to their corresponding linear amides. Mechanistic studies reveal a reversible rhodium hydride migratory insertion step, leading to exquisite selectivity for the anti-Markovnikov product.

CuCl2 -Catalyzed α-Chloroketonation of Aromatic Alkenes via Visible-Light-Induced LMCT.

Here we report a copper-catalyzed protocol for the synthesis of α-chloroketones from aromatic alkenes including electron-deficient olefins under visible-light irradiation. Preliminary mechanistic studies show that the peroxo Cu(II) species is the key intermediate and hydroperoxyl (HOO⋅) and chlorine (Cl⋅) radicals can be generated by ligand-to-metal charge transfer (LMCT).

A Neutral FeCl3 Photocatalysis for C–C Bond Animation and Alkylation of Cyclic Alcohols

AbstractA modified method for iron-catalyzed C–C bond cleavage and amination and alkylation of nonactivated cyclic alcohols has been developed. Using FeCl3 as catalyst, the photoinduced ligand-to-metal charge transfer facilitates the generation of O-radicals from alcohols, the subsequent β-scission, and finally the radical trapping. Compared with the Fe(OR)3 catalysis, this mildly base-free system could enable the amination in a broader substrate scope with higher yields. Moreover, the C–C bond cleavage and alkylation of cyclic alcohols proceeds with electron-deficient olefins under these conditions.

Iron-Catalyzed C-H Activation for Heterocoupling and Copolymerization of Thiophenes with Enamines.

C-H/C-H coupling via C-H activation provides straightforward synthetic access to the construction of complex π-conjugated organic molecules. The palladium-catalyzed Fujiwara-Moritani (FM) coupling between an arene and an electron-deficient olefin presents an early example but is not applicable to enamines such as N-vinylcarbazoles and N-vinylindoles. We report herein iron-catalyzed C-H/C-H heterocoupling between enamines and thiophenes and its application to copolymerization of bisenamine and bisthiophene using diethyl oxalate as an oxidant and AlMe3 as a base, as a result of our realization that synthetic limitations in oxidative C-H/C-H couplings imposed by the high redox potential of the Pd(II)/Pd(0) catalytic cycle can be circumvented by the use of iron, which has a lower Fe(III)/Fe(I) redox potential. The trisphosphine ligand provides a coordination environment for iron to achieve the reaction's regio-, stereo-, and chemoselectivity. The reaction includes C-H activation of thiophene via σ-bond metathesis and subsequent enamine C-H cleavage triggered by nucleophilic enamine addition to the Fe(III) center, thereby differing from the FM reaction in mechanism and synthetic scope. The copolymers synthesized by the new reaction possess a new type of enamine-incorporated polymer backbone.

Preparation of Thietane Derivatives through Domino Photochemical Norrish Type II/Thia-Paternò-Büchi Reactions.

This work describes straightforward access to a large collection of thietane derivatives through an innovative two-step domino photochemical reaction involving a Norrish type II fragmentation and a thia-Paternò-Büchi reaction. Starting from stable phenacyl sulfides, unprecedented thiocarbonyl intermediates were generated in situ and reacted with diverse electron-deficient alkene partners to form a thietane core. The rules governing the regio- and diastereoselectivity of this [2+2] photocycloaddition have been rationalized and fully controlled for many substrates.

Ru-Catalyzed Benzannulation of Vinyl Sulfoxonium Ylide with Electron-Deficient Alkynes and Alkenes.

Herein, we report carbene-mediated benzannulation of vinyl sulfoxonium ylides with electron-deficient alkynes and alkenes to synthesize oxygenated arenes. This protocol features excellent regioselectivity, a broad substrate scope, and mild reaction conditions. Mechanistic studies revealed that the reaction proceeds through furan generation, cycloaddition, ring cleavage, and aromatization cascades. The synthesized arenes have been utilized in diverse product transformations and arene ring homologation.

Nickel-Catalyzed Radical Heck-Type C(sp3)-C(sp2) Coupling Cascades Enabled by Bromoalkane-Directed 1,4-Aryl Shift: Access to Olefinated Arylalanines.

A bromoalkane-directed radical 1,4-aryl shift strategy for nickel-catalyzed reductive Heck-type C(sp3)-C(sp2) coupling cascades of α-amino-β-bromocarboxylic acid esters with α-trifluoromethyl alkenes for producing gem-difluorinated arylalanines is presented. The α-aminoalkyl radicals generated from neophyl-type aryl migration function as robust coupling partners to allow for further Giese-type addition with electron-deficient α-trifluoromethyl alkenes and vinyl sulfones, thereby realizing a new radical cascade for the simultaneous installation of an aromatic ring and olefin motif into amino acid backbones.

Pincer-nickel catalyzed asymmetric addition of HPPh2 to enones toward the synthesis of chiral phosphines

The catalytic synthesis of chiral phosphines has been accomplished by the asymmetric addition of phosphine to electron-deficient alkenes in the presence of the newly developed unsymmetric pincer-nickel complex. Various chiral phosphines were obtained in 61–92% yields with up to 98% ee.

Design, synthesis and antitumor activity of potent and safe para-quinone methides derivatives in vitro and in vivo

Compounds containing Michael acceptor units display a wide variety of biological effects, and have attracted much attention in medicinal chemistry. In this paper, we designed and synthesized a panel of para-quinone methides (p-QMs) derivatives, classified as electron-deficient alkenes, and evaluated their cytotoxicity against cancer cells. These results revealed that drawing substituents into the ortho-position of the phenyl ring could obviously strengthen the cytotoxicity of p-QMs derivatives compared with that of meta- and para-substituents. Further biological studies demonstrated that the cytotoxicity of p-QMs derivatives originated from their ROS-generation abilities, which could further disrupt the redox balance, lipid peroxidation, the loss of MMP, cell cycle arrest at G0/G1 phase and apoptosis. 1h also exhibited potent antitumor activity through inhibiting TrxR and activating Bax and caspase 3 expression in vitro and in vivo, and 1h had certain safety in vivo. Moreover, the electrophilicity of the Michael acceptor, which could covalently modify with the TrxR, play a potent role in the ROS generation. From the perspective of chemistry, we affirmed that p-QMs derivatives could rapidly covalent binding with cysteamine, and the addition product was characterized by 1H NMR. Together, these new p-QMs derivatives may possess potential as leads for development of effective antitumor agents.

Photoredox-Catalyzed Deoxygenation of Hexafluoroacetone Hydrate Enables Hydroxypolyfluoroalkylation of Alkenes.

An unprecedented photoredox-catalyzed phosphine-mediated deoxygenation of hexafluoroacetone hydrate was established to accomplish the hydroxylpolyfluoroalkylation of electron-deficient alkenes. A range of bis(trifluoromethyl)carbinols were facilely accessed by using readily available hexafluoroacetone hydrate, instead of toxic gaseous hexafluoroacetone. A range of electron-deficient alkenes are tolerated, giving the corresponding hydro-hydroxylpolyfluoroalkylated products in moderate to high yields. Remarkable features of this synthetic strategy include operational simplicity, mild reaction conditions, excellent regioselectivity, and broad functional group tolerance. The success of this strategy relies on the delicate utilization of aldehyde/ketone-gem-diol intrinsic equilibrium, which offers an innovated open-shell pathway for the assembly of synthetically challenging polyfluoroalkylated scaffolds.

Photocatalytic Generations of Secondary and Tertiary Silyl Radicals from Silylboranes Using an Alkoxide Cocatalyst.

Silyl radicals are valuable species to prepare diverse organosilicon compounds. However, unlike stable tertiary silyl radicals, the use of secondary silyl radicals has been problematic in silylation reactions due to their instability. Here, we present photocatalytic in situ generations of both secondary and tertiary silyl radicals by one-electron oxidation of ate complexes, formed from silylboranes and an alkoxide cocatalyst, achieving highly efficient hydrosilylation and deuterosilylation of electron-rich alkenes and dienes as well as electron-deficient alkenes. The theoretical studies show that anionic borate complexes activated with an alkoxide have lower oxidation potentials than neutral borate complexes, allowing the formation of secondary silyl radicals. The calculated reaction pathways reveal that anionic conditions using the conjugate acid-base pair of NaOEt (cocatalyst) and EtOH (solvent) are the key to expanding the scope of silyl radicals and alkenes.

Eosin Y-Catalyzed Visible-Light-Induced Hydroperfluoroalkylation of Electron-Deficient Alkenes.

The eosin Y-catalyzed hydroperfluoroalkylation of electron-deficient alkenes is described herein. The reaction proceeded smoothly under visible light irradiation and selectively afforded a hydroperfluoroalkylated product. Various perfluoroalkyl bromides and electron-deficient olefins can be used in this reaction, and all chemicals required for this reaction are safe and readily available.

Pd-catalyzed siloxycyclopropanation of alkenes

Unlike electron-deficient and electronically neutral carbenes, alkoxycarbenes, a class of electron-rich carbenes, cannot be used in metal-catalyzed cyclopropanation reactions due to the instability of the corresponding carbene precursors (i.e., diazoalkanes). Although siloxycarbenes can be generated from acylsilanes under photoirradiation or heating at a temperature above 250°C, except for electron-deficient alkenes, the resulting electron-rich carbenes do not react with alkenes.

Copper-Catalyzed Cross-Coupling Between (E)-1,2-Diiodoethene and Carbazates: Entry to β-Functionalized N-Alkenylcarbazates

Aims: This work aims to widen the scope of methodologies to prepare functionalized N-alkenylcarbazates. Background: Alkenylcarbazates are generally prepared via Aza-Baylis-Hillman reactions, nucleophilic attack on ketones or a tandem carbometallation/amidation reaction of alkynes. Objective: The objective of this work is to develop a method to prepare functionalized Nalkenylcarbazates that alleviates the problem encountered in the above methods (use of electron deficient alkenes, use of stoiechiometric amounts of metal, access to symmetrical dicarbazates only). Methods: Use of copper-catalyzed cross-coupling between vinylic diiodide and carbazates to prepare functionalized N-alkenylcarbazates. Results: Various β-iodovinylcarbazates were synthesized with up to good yields. The highest yields were obtained using dicarbazates. Functionalization of β-iodovinylcarbazate demonstrated that the vinyl iodide moiety of these molecules can be substituted by a variety of functional groups via transition metal-catalyzed coupling reactions. Conclusion: Copper-catalyzed cross-coupling reaction is efficient to prepare functionalized N-alkenylcarbazates.

Activation Mechanism of Nickel(0) N-Heterocyclic Carbene Catalysts Stabilized by Fumarate Ligands.

Nickel(0) catalysts of N-heterocyclic carbenes (NHCs) that are stabilized by electron-deficient alkenes possess desirable properties of air tolerance and ease of handling while also retaining high catalytic activities. Since catalyst stability often comes at the expense of catalytic activity, we have undertaken a detailed study of the activation mechanism of an IMes-nickel(0) catalyst stabilized by di(o-tolyl) fumarate that converts the stable precatalyst form into a catalytically active species. Computational evaluation provided evidence against a simple ligand exchange as the activation mechanism for this catalyst, and a stoichiometric activation process that covalently modifies the stabilizing ligand was identified. A detailed computational picture for the activation process was developed, with predictive insights that elucidate an unexpected catalyst activation pathway that operates when ligand exchange is thermodynamically unfavorable.