Unbiased Alkenes Research Articles

Electrochemically enabled (3+2) cycloaddition of unbiased alkenes and β-dicarbonyls.

A (3+2) cycloaddition between unbiased alkenes and 1,3-dicarbonyls is accomplished by judicious choice of electrode material and electrocatalyst to access dihydrofuran derivatives. A fluorinated porous carbon electrode with appropriate thickness governs unprecedented reactivity. This methodology eliminates the necessity for any stabilizing group within the alkene substrate. This is a rare example of the annulation of unbiased internal and terminal alkenes with cyclic and acyclic β-dicarbonyls.

The xanthate route to tetralones, tetralins, and naphthalenes. A brief account.

The present account summarises routes to tetralones, tetralines, and naphthalenes based on the chemistry of xanthates developed in the authors' laboratory. The degenerative reversible transfer of xanthates allows radical addition even to unactivated, electronically unbiased alkenes, and tolerates a broad range of functional groups, in particular common polar groups such as esters, ketones, nitriles, amides, carbamates, etc. Xanthates also allow radical ring closures onto aromatic rings. This feature, in combination with the intermolecular addition to alkenes, can be used to construct tetralones and tetralines. With the appropriate appendages, the former can be converted into napthalenes with a variety of substitution patterns. This translates into a convergent approach to a vast array of building blocks of interest to the pharmaceutical and agrochemical industries, and to material sciences.

Selective Three-Component Reductive Alkylalkenylation of Unbiased Alkenes via Carbonyl-Directed Nickel Catalysis

Selective Three-Component Reductive Alkylalkenylation of Unbiased Alkenes via Carbonyl-Directed Nickel Catalysis

Palladium and Amino Acid Co-Catalyzed Highly Regio- and Enantioselective Hydroarylation of Unbiased Alkenes

Palladium and Amino Acid Co-Catalyzed Highly Regio- and Enantioselective Hydroarylation of Unbiased Alkenes

Transition‐Metal‐Catalyzed, Chelation‐Assisted C−H Alkenylation and Allylation of Organic Molecules with Unactivated Alkenes

AbstractOlefins are important building blocks and are widely utilized in synthetic organic chemistry. Owing to its omnipresence and unique reactivity, the functionalization of alkenes has become a powerful method for constructing complex organic molecules. In this context, direct chelation‐assisted C−H olefination at the inert C−H bonds represents the most straightforward synthetic method for introducing the alkenyl group into organic compounds in a highly regio‐ and stereoselective manner. Despite the remarkable advances in chelation‐assisted C−H olefination reaction, most of the successful transformations are restricted to activated or electronically biased olefins such as acrylates, styrenes, acrylamides, vinyl sulfones, and vinyl phosphonates. Literature reports on chelation‐assisted C−H olefination with unactivated or electronically unbiased alkenes are limited due to poor intrinsic reactivity and regioselectivity issues. Despite significant challenges, the past few years have witnessed tremendous growth. The present review describes the recent advances in the chelation‐assisted C−H olefination and allylation of aromatics, alkenes, and heteroaromatics with unactivated alkenes via the concerted‐metallation‐ deprotonation pathway.Transition metals such as palladium, rhodium, iridium and cobalt are widely used for these kind of transformations. The scope, mechanistic investigation, and limitation of the alkenylation and allylation reactions are discussed elaborately. The present review includes all the reported C−H olefination and allylation reactions with unactivated olefins via the base‐assisted deprotonation pathway.magnified image

Intermolecular 2+2 imine-olefin photocycloadditions enabled by Cu(I)-alkene MLCT

2 + 2 Photocycloadditions are idealized, convergent construction approaches of 4-membered heterocyclic rings, including azetidines. However, methods of direct excitation are limited by the unfavorable photophysical properties of imines and electronically unbiased alkenes. Here, we report copper-catalyzed photocycloadditions of non-conjugated imines and alkenes to produce a variety of substituted azetidines. Design principles allow this base metal-catalyzed method to achieve 2 + 2 imine-olefin photocycloaddition via selective alkene activation through a coordination-MLCT pathway supported by combined experimental and computational mechanistic studies.

A Practical Route to Cyclobutanols and Fluorocyclobutanes

Abstract1‐[(Ethoxycarbonothioyl)sulfanyl]cyclobutyl acetate (xanthate 7) was found to add to electronically unbiased alkenes and to certain heteroarenes. In the latter case, this corresponds to a variant of the Minisci reaction and allows the late‐stage modification of biologically active substances. Saponification of the acetate furnishes the corresponding cyclobutanols, which, in the case of the nicotine adduct, can be converted into fluorocyclobutanes by the action of DAST. Fluorocyclobutyl substituted aromatics and heteroaromatics are increasingly present in drug candidates. Heating of the acetoxycyclobutyl derivative of caffeine with TFA gives rise to the cyclobutene analogue. Finally, O‐ethyl S‐[1‐(2,2,2‐trifluoroethoxy)cyclobutyl] carbonodithioate, obtained unexpectedly while optimizing the synthesis of xanthate 7, is a very promising reagent for the introduction of the very rare 2,2,2‐trifluoroethoxycyclobutyl motif.

Iron-Catalyzed Radical Intermolecular Addition of Unbiased Alkenes to Aldehydes.

The intermolecular reductive radical coupling of aldehydes with nonactivated alkenes, employing metal hydride atom transfer (MHAT) catalysis with a combination of FeII and FeIII salts, is described. This constitutes the first use of aldehydes as viable acceptor groups in MHAT reactions. The insights gained in this study led to the reexamination of the previously reported intramolecular version of the reaction, and the addition of FeII salts allowed the development of a more efficient second-generation approach.

Recent advances in nickel-catalyzed reductive hydroalkylation and hydroarylation of electronically unbiased alkenes

The use of simple and easily available feedstock to quickly and efficiently obtain compounds with complex molecular structures through the transition-metal-catalyzed construction of C(sp3)–C bonds has important significance. As traditional C(sp3)–C coupling reagents, alkylmetallic reagents often have limitations such as air and moisture sensitivity and difficulties in storage. Nickel-catalyzed reductive olefin hydrocarbonation reactions use alkenes to replace organometallic reagents, reduce the synthesis steps, improve the functional group compatibility, and expand the substrate scope. This minireview discusses important progress in the hydroalkylation and hydroarylation of electronically unbiased alkenes in recent years and describes the key mechanism and applications.

Recent Advances in Silver‐Catalyzed Transformations of Electronically Unbiased Alkenes and Alkynes

AbstractSilver, as one of the most ancient coinage metals, has attracted a plethora of attention from chemists in recent years due to the easy availability, high catalytic efficiency and multiple functions displayed in various chemical processes. In particular, the research in this field has gained a great progress since 2007 and several elegant reviews have been documented in the literature. However, there has been no systematic review concentrating on the transformations of electronically unbiased alkenes and alkynes under silver catalysis till now, though a rapid development in this area is witnessed. Therefore, this review mainly focuses on the recent advances in silver‐catalyzed reactions of different electron‐unbiased alkenes and alkynes, covering examples of hydrofunctionalization reactions, difunctionalization reactions, cross‐coupling reactions as well as cyclization reactions since 2015 to February 2020. In addition, some interesting mechanisms were also discussed.

Versatility and adaptative behaviour of the P^N chelating ligand MeDalphos within gold(i) π complexes.

The hemilabile P^N ligand MeDalphos enables access to a wide range of stable gold(i) π-complexes with unbiased alkenes and alkynes, as well as electron-rich alkenes and for the first time electron-poor ones. All complexes have been characterized by multi-nuclear NMR spectroscopy and whenever possible, by X-ray diffraction analyses. They all adopt a rare tricoordinate environment around gold(i), with chelation of the P^N ligand and side-on coordination of the alkene, including the electron-rich one, 3,4-dihydro-2H-pyrane. The strength of the N → Au coordination varies significantly in the series. It is the way the P^N ligand accommodates the electronic demand at gold, depending on the alkene. Comparatively, when the chelating P^P ligand (ortho-carboranyl)(PPh2)2 is used, gold(i) π-complexes are only isolable with unbiased alkenes. The bonding situation within the gold(i) P^N π-complexes has been thoroughly analyzed by DFT calculations supplemented by Charge Decomposition Analyses (CDA), Natural Bond Orbital (NBO) and Atoms-in-Molecules (AIM) analyses. Noticeable variations in the donation/back-donation ratio, C Created by potrace 1.16, written by Peter Selinger 2001-2019 ]]> C weakening, alkene to gold charge transfer and magnitude of the N → Au coordination were observed. Detailed examination of the descriptors for the Au/alkene interaction and the N → Au coordination actually revealed intimate correlation between the two, with linear response of the MeDalphos ligand to the alkene electronics. The P^N ligand displays non-innocent and adaptative character. The isolated P^N gold(i) π-complexes are reactive and catalytically relevant, as substantiated by the chemo and regio-selective alkylation of indoles.

Intermolecular Phosphite-Mediated Radical Desulfurative Alkene Alkylation Using Thiols

We report herein the development of aS atom transfer process using triethyl phosphite as the S atom acceptor that allows thiols to serve as precursors of C-centered radicals. A range of functionalized and electronically unbiased alkenes including those containing common heteroatom-based functional groups readily participate in this reductive coupling. This process is driven by the exchange of relatively weak S-H and C-S bonds of aliphatic thiols for C-H, C-C, and S-P bonds of the products formed.

Radical Alliances: Solutions and Opportunities for Organic Synthesis

AbstractThe present account discusses in detail various mechanistic features of the degenerative radical addition‐transfer of xanthates and related thiocarbonylthio congeners and makes a comparison with the more classical Kharasch reactions to which it is similar in certain aspects. The xanthate group reacts reversibly with the ‘active’ radicals in the medium and is able to store them in a somewhat inactive form. This increases their effective lifetime in the medium and, at the same time, lowers their absolute concentration while regulating their relative concentration. These properties translate into a powerful carbon–carbon bond forming process, especially as regards intermolecular additions to electronically unbiased (‘unactivated’) alkenes. Most functional groups are tolerated, in particular polar functions that often require protection with other chemistries. This broad versatility is illustrated by examples where the xanthate addition to the alkene is combined with other, more classical reactions to provide a convergent, rapid access to a wide range of useful structures. Emphasis has been placed on the synthesis of open chain and more complex carbocycles, as well as on the transfer of chirality. These ‘radical alliances’ include organosilicon chemistry, the Diels–Alder cycloaddition and cheletropic extrusion of sulfur dioxide, the Claisen sigmatropic rearrangement, and the Horner–Wadsworth–Emmons (HWE) condensation.

Olefin Hydroarylation via Ni/Co Dual Catalysis

Cobalt/nickel dual-catalysis enables the branch-selective hydroarylation of olefins through a novel "cage-rebound" transmetalation pathway. This process allows for the rapid introduction of complexity by coupling readily available iodoarenes with abundant and unbiased alkenes without the need for substrate prefunctionalization.

Nickel‐Catalyzed 1,1‐Alkylboration of Electronically Unbiased Terminal Alkenes

AbstractAn unprecedented nickel‐catalyzed 1,1‐alkylboration of electronically unbiased alkenes has been developed, providing straightforward access to secondary aliphatic boronic esters from readily available materials under very mild reaction conditions. The regioselectivity of this reaction is governed by a unique pyridyl carboxamide ligated catalyst, rather than the substrates. Moreover, this transformation shows excellent chemo‐ and regio‐selectivity and remarkably good functional‐group tolerance. We also demonstrate that under balloon pressure, ethylene can also be utilized as a substrate. Additionally, competence experiments indicate that selective bond formation is favored at the α‐position of boron and preliminary mechanistic studies indicate that the key step in this three‐component reaction involves a 1,2‐nickel migration.

Nickel-Catalyzed 1,1-Alkylboration of Electronically Unbiased Terminal Alkenes.

An unprecedented nickel-catalyzed 1,1-alkylboration of electronically unbiased alkenes has been developed, providing straightforward access to secondary aliphatic boronic esters from readily available materials under very mild reaction conditions. The regioselectivity of this reaction is governed by a unique pyridyl carboxamide ligated catalyst, rather than the substrates. Moreover, this transformation shows excellent chemo- and regio-selectivity and remarkably good functional-group tolerance. We also demonstrate that under balloon pressure, ethylene can also be utilized as a substrate. Additionally, competence experiments indicate that selective bond formation is favored at the α-position of boron and preliminary mechanistic studies indicate that the key step in this three-component reaction involves a 1,2-nickel migration.

Intermolecular Heck Coupling with Hindered Alkenes Directed by Potassium Carboxylates

AbstractPd0‐catalyzed Mizoroki–Heck reactions traditionally exhibit poor reactivity with polysubstituted, unbiased alkenes. Intermolecular reactions with simple, all‐carbon tetrasubstituted alkenes are unprecedented. Herein we report that pendant carboxylic acids, combined with bulky monophospine ligands on palladium, can direct the arylation of tri‐ and tetrasubstituted olefins. Quaternary carbons are established at high Fsp3 attached‐ring junctures and the carboxylate directing group can be removed after coupling. Carboxylate directivity prevents over‐arylation of the new, less substituted alkene, which can be diversified in subsequent reactions.

Intermolecular Heck Coupling with Hindered Alkenes Directed by Potassium Carboxylates.

Pd0 -catalyzed Mizoroki-Heck reactions traditionally exhibit poor reactivity with polysubstituted, unbiased alkenes. Intermolecular reactions with simple, all-carbon tetrasubstituted alkenes are unprecedented. Herein we report that pendant carboxylic acids, combined with bulky monophospine ligands on palladium, can direct the arylation of tri- and tetrasubstituted olefins. Quaternary carbons are established at high Fsp3 attached-ring junctures and the carboxylate directing group can be removed after coupling. Carboxylate directivity prevents over-arylation of the new, less substituted alkene, which can be diversified in subsequent reactions.

Thiophene-Alkyne-Based CMPs as Highly Selective Regulators for Oxidative Heck Reaction.

Thiophenes containing an adjacent C≡C group as ligands for PdII-promoted organic reactions are reported for the first time. These ligands were utilized as catalytic sites and integrated into the skeleton of conjugated microporous polymers. By employing these CMP materials as selective regulators, oxidative Heck reactions between arylboronic esters and electronically unbiased alkenes provide highly selective linear products.

Mechanism of Aldehyde-Selective Wacker-Type Oxidation of Unbiased Alkenes with a Nitrite Co-Catalyst

Traditional Wacker-type oxidations of unbiased alkenes produce ketones as major products. Recently, Grubbs’ group reported a Wacker-type oxidation system in which aldehydes (rather than ketones) have been generated predominantly in the presence of a nitrite co-catalyst. To elucidate the mechanistic origin of the aldehyde selectivity, density functional theory (DFT) studies have been conducted in this study. Two oxymetalation pathways, i.e., syn addition and anti addition pathways, were considered for various possible active species including monomeric Pd, bimetallic Pd–Pd, heterobimetallic Pd–Cu, and heterobimetallic Pd–Ag complexes. It is found that syn addition is kinetically more favored than anti addition in general. Meanwhile, the most feasible oxymetalation processes occur on the heterobimetallic Pd–Cu complexes. Investigations on the subsequent aldehyde formation process show that 1,2-H shift mechanism on tBuOH-ligated Pd–Cu complexes is superior to the betaH-elimination mechanism. Besides, the 1,2...