Functionalization Of Alkanes Research Articles

Recyclable Aliphatic Nitrile-Template Enabled Remote meta-C-H Functionalization at Room Temperature.

This article describes the development of a new aliphatic nitrile-template-directed remote meta-selective C-H olefin functionalization reaction of arenes. Remarkably, unlike the previous reports, this process is feasible at room temperature and enabled the formation of products with excellent regioselectivity. The present protocol encompasses a broad spectrum of substituted dihydrocinnamic acids and olefins, producing meta-C-H olefinated products (up to 96% yield). In addition, the efficacy of the present method has been showcased by the synthesis of various drug analogues (e.g., cholesterol, estrone, ibuprofen, and naproxen). Significantly, the robustness of meta-olefination was also demonstrated by gram-scale synthesis. The new nitrile-based meta-directing template, in particular, could be easily synthesized in two steps and recycled under mild conditions.

Recent Advances in the Smiles Rearrangement: New Opportunities for Arylation

AbstractThe Smiles rearrangement has undergone a renaissance in recent years providing new avenues for non-canonical arylation techniques in both the radical and polar regimes. This short review will discuss recent applications of the reaction (from 2017 to late 2021), including its relevance to areas such as heterocycle synthesis and the functionalization of alkenes and alkynes as well as glimpses at new directions for the field.1 Introduction2 Polar Smiles Rearrangements3 Radical Smiles: Alkene and Alkyne Functionalization4 Radical Smiles: Rearrangements via C–X Bond Cleavage5 Radical Smiles: Miscellaneous Rearrangements6 Conclusions

Aromatic π-Components for Enantioselective Heck Reactions and Heck/Anion-Capture Domino Sequences.

Olefin functionalization represents one of the most important synthetic transformations in organic synthesis. Over the past decades, palladium-catalyzed enantioselective Heck reactions, and Heck/anion-capture domino sequences through olefin carbopalladation followed by termination of the resulting alkyl-Pd species have been extensively developed. Extension of the coupling partners from classical olefins to other π-components would enable further advances and open new space in this field. Aromatics are important and easily available bulk chemicals. Dearomative transformation of endocyclic aromatic π-bonds via the Heck reaction pathway provides an efficient and straightforward route to structurally diverse alicyclic compounds. Nevertheless, major challenges for this transformation include aromaticity breaking and reactivity and selectivity issues.Recently, we have engaged in developing catalytic enantioselective dearomative Heck reactions and related domino reactions. A range of heteroarenes and naphthalenes have been employed as novel π-coupling partners in these reactions. Through dearomative migratory insertion of endocyclic aromatic C-C π-bonds followed by interception of the transient alkyl-Pd species, enantioselective Heck reactions, reductive Heck reactions, Heck/anion-capture difunctionalization reactions, and heteroarenyne cycloisomerization reactions have been established. Relying on β-H elimination of the alkyl-Pd intermediate, we realized enantioselective dearomative Heck reactions with a range of aromatic partners, including heterocyclic indoles, pyrroles, furans, benzofurans, and more challenging carbocyclic naphthalenes. In order to avoid the utilization of organohalide electrophiles, heteroarenyne cycloisomerization reaction was developed by merging intermolecular alkyne hydropalladation with intramolecular dearomative Heck reaction. Cycloisomerization of alkyne-tethered indoles delivered chiral indolines in excellent enantioselectivities with 100% atom economy. On the other hand, Heck/anion-capture domino sequences were established through nucleophilic trapping of the alkyl-Pd intermediate. When HCO2Na was employed as a capturing reagent, the enantioselective dearomative reductive Heck reaction of indoles was realized. By employing other nucleophiles, including alkynes, N-sulfonylhydrazones, and organoboron reagents, we developed a series of dearomative difunctionalization reactions. Two vicinal stereocenters with excellent enantio- and diastereoselectivities were constructed in the corresponding Heck/Sonogashira, Heck/vinylation, and Heck/borylation reactions. Moreover, dearomative 1,4-diarylation of naphthalenes was developed through Heck/Suzuki domino reactions, in which competitive C-H arylation and the direct Suzuki reaction were almost fully inhibited in the presence of a spiro-phosphoramidite ligand.In this Account, we provide a panoramic view of our results since 2015 on enantioselective Heck reactions and related domino sequences by extending the coupling partners from classical olefins to aromatic systems. Investigations outlined in this Account established straightforward and efficient access to a variety of structurally diverse chiral heteropolycyclic molecules starting from simple and planar aromatic compounds.

Asymmetric Cyclopropanation and Epoxidation via a Catalytically Formed Chiral Auxiliary.

For the enantioselective diversification of a single starting material, a different chiral catalyst is usually required for each transformation. Herein, we extend the concept of catalytically formed chiral auxiliary from hydrogenation to the asymmetric cyclopropanation and epoxidation of tetra‐substituted olefins, alleviating the need for different chiral catalysts in the alkene functionalization step. The chiral auxiliary is catalytically constructed from propargylic amines in a Pd‐catalyzed enantioselective carboetherification step using a commercially available trifluoroacetaldehyde hemiacetal tether. The installed auxiliary is then controlling the stereochemistry of the cyclopropanation and the epoxidation using standard highly reactive reagents to give enantioenriched spirocyclic aminomethylcyclopropanols and α‐amino‐α‐hydroxy ketones.

Asymmetric Cyclopropanation and Epoxidation via a Catalytically Formed Chiral Auxiliary

AbstractFor the enantioselective diversification of a single starting material, a different chiral catalyst is usually required for each transformation. Herein, we extend the concept of catalytically formed chiral auxiliary from hydrogenation to the asymmetric cyclopropanation and epoxidation of tetra‐substituted olefins, alleviating the need for different chiral catalysts in the alkene functionalization step. The chiral auxiliary is catalytically constructed from propargylic amines in a Pd‐catalyzed enantioselective carboetherification step using a commercially available trifluoroacetaldehyde hemiacetal tether. The installed auxiliary is then controlling the stereochemistry of the cyclopropanation and the epoxidation using standard highly reactive reagents to give enantioenriched spirocyclic aminomethylcyclopropanols and α‐amino‐α‐hydroxy ketones.

Synthetic Studies on the Synthesis of Toxicodenane A and 8,11-epi-Toxicodenane A

The diverse synthesis of oxatricyclotridecanes and oxatricyclododecanes, which are the core structures of toxicodenane A and its skeletal analogues, via a unified manner is presented. The stereochemistry at the bridgehead position of the oxa-bridged bicycle could be efficiently controlled through a diastereoselective anti- and syn-Grignard allylation reaction by appropriately tuning the reaction conditions such as the solvent, the counterion of the Grignard reagent, the substrate, or a combination of these. The ring size could be precisely elaborated via a Lewis acid-mediated intramolecular transacetalation and Prins cyclization cascade reaction by varying the steric hindrance of olefin moiety. Namely, substrates bearing a terminally unsubstituted olefinic functionality afforded oxatricyclotridecanes with an overwhelming preference, while those bearing a dimethyl-substituted olefinic group produced exclusively oxatricyclododecanes. The wide utility and generality of the above key transformations are highlighted by the applications in the unified synthesis of (±)-toxicodenance A, (+)-toxicodenane A, (+)-8,11-epi-toxicodenane A, and other oxatricyclic cores with different stereochemistries and ring sizes.

Controllable access to trifluoromethyl-containing indoles and indolines: palladium-catalyzed regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides.

The synthesis of diverse products from the same starting materials is always attractive in organic chemistry. Here, a palladium-catalyzed substrate-controlled regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides has been developed, which provides a direct but controllable access to a variety of structurally diverse trifluoromethyl-containing indoles and indolines. In more detail, with respect to γ,δ-alkenes, 1,1-geminal difunctionalization of unactivated alkenes with trifluoroacetimidoyl chloride enables the [4 + 1] annulation to produce indoles; as for β,γ-alkenes, a [3 + 2] heteroannulation with the hydrolysis product of trifluoroacetimidoyl chloride through 1,2-vicinal difunctionalization of alkenes occurs to deliver indoline products. The structure of alkene substrates differentiates the regioselectivity of the reaction.

Radical addition to the CC bond meets (1,n)-HAT: recent advances in the remote C(sp3)–H or C(sp2)–H functionalization of alkenes

This review summarizes the recent development of remote C(sp3)–H bond or aldehydic C(sp2)–H functionalizations enabled by intermolecular radical addition to CC bond/(1,n)-HAT tandem sequences.

Recent advances in visible-light-mediated functionalization of olefins and alkynes using copper catalysts.

Over the past decade, visible-light photoredox catalysis has blossomed as a powerful strategy and offers a discrete activation mode complementary to thermal controlled reactions. Visible-light-mediated photoredox catalysis also offers exciting opportunities to achieve challenging carbon-carbon and carbon-heteroatom bond formations with excellent chemo-, regio-, or stereoselectivity under mild and ecologically benign conditions. The greater part of photoredox reactions depends on heavy metals like ruthenium(II) or iridium(III) based complexes as photoredox catalysts owing to their strong absorption, long-lived excited-state lifetimes and high oxidation or redox potentials. However, these transition metal complexes are expensive and pose severe drawbacks with respect to large scale application and sustainability. Organic dyes are also commonly used as a low-cost alternative to Ru- or Ir-based complexes. However, they have inferior photostability. Thus, further development of alternative photocatalysts based on copper salts or copper complexes is widely investigated because of their economic and environmental benefits. In recent years, visible-light-mediated direct functionalization of olefins or alkynes to afford a diverse range of organic compounds has received extensive interest from synthetic chemists due to their easy availability and reactivity towards a large number of reactants. In this review, we have highlighted the most recent significant advances that have been made in the use of copper-based photocatalysts for the functionalization of olefins and alkynes with an emphasis on substrate scope, limitations, mechanistic understanding and applications of these reactions. This review covers the literature from 2015 to 2021.

Selective C(sp2)-H bond functionalization of olefins via visible-light-induced photoredox-quinuclidine dual catalysis.

The site selective C(sp2)-H bond functionalization of olefins has been achieved through a visible-light-induced photoredox-quinuclidine dual catalysis upon merging the quinuclidinium radical cation addition to alkene strategy and the distal heteroaryl ipso-migration strategy. This synthetic protocol features a simple operation with readily available starting materials in good step-economy to access alkenylheteroaromatic products in moderate to good yields under mild conditions. A plausible cascade catalytic reaction mechanism is also proposed.

Regio- and stereo-selective olefinic C–H functionalization of aryl alkenes in ethanol

We report on α- and β-olefinic C–H alkenylation of 2-alkenyl benzylamine/benzoic acid derivatives in ethanol to afford aryl dienes/trienes with excellent selectivities, proceeding through 6-/7-membered exo-/endo-cyclometallation.

Correction: Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles

Correction for 'Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles' by Anjali Dahiya et al., Org. Biomol. Chem., 2022, DOI: 10.1039/d1ob02233d.

Electro-/photocatalytic alkene-derived radical cation chemistry: recent advances in synthetic applications.

Alkene-derived radical cations are versatile reactive intermediates and have been widely applied in the construction of complex functionalized molecules and cyclic systems for chemical synthesis. Therefore, the synthetic application of these alkene-derived radical cations represents a powerful and green tool that can be used to achieve the functionalization of alkenes partially because the necessity of stoichiometric external chemical oxidants and/or hazardous reaction conditions is eliminated. This review summarizes the recent advances in the synthetic applications of the electro-/photochemical alkene-derived radical cations, emphasizing the key single-electron oxidation steps of the alkenes, the scope and limitations of the substrates, and the related reaction mechanisms. Using electrocatalysis and/or photocatalysis, single electron transfer (SET) oxidation of the CC bonds in the alkenes occurs, generating the alkene-derived radical cations, which sequentially enables the functionalization of translocated radical cations to occur in two ways: the first involves direct reaction with a nucleophile/radical or two molecules of nucleophiles to realize hydrofunctionalization, difunctionalization and cyclization; and the second involves the transformation of the alkene-derived radical cations into carbon-centered radicals using a base followed by radical coupling or oxidative nucleophilic coupling.

Co-Catalyzed C(sp3)–C(sp2) bond cleavageviahydrogen atom transfer

A new HAT-initiated C(sp3)–C(sp2) bond cleavage approach enabling the functionalization of alkenes to ketones is presented.

SOMOphilic Alkynylation of Unreactive Alkenes Enabled by Iron-Catalyzed Hydrogen Atom Transfer

We report an efficient and practical iron-catalyzed hydrogen atom transfer protocol for assembling acetylenic motifs into functional alkenes. Diversities of internal alkynes could be obtained from readily available alkenes and acetylenic sulfones with excellent Markovnikov selectivity. An iron hydride hydrogen atom transfer catalytic cycle was described to clarify the mechanism of this reaction.

Vicinal Difunctionalization of Alkenes Using Vinyl Triflates Leading to γ-Trifluoromethylated Ketones

We report a new methodology for the synthesis of γ-trifluoromethylated ketones from alkenes and vinyl triflate bifunctional reagents. The reaction proceeds via the addition of a β-trifluoromethyl alkyl radical to a vinyl triflate, followed by β-cleavage. We also demonstrate a one-pot version of the reaction for the vicinal functionalization of alkenes from alkynes.

Electrochemical Synthesis of Allylic Amines from Terminal Alkenes and Secondary Amines

Allylic amines are valuable synthetic targets en route to diverse biologically active amine products. Current allylic C-H amination strategies remain limited with respect to the viable N-substituents. Herein, we disclose a new electrochemical process to prepare aliphatic allylic amines by coupling two abundant starting materials: secondary amines and unactivated alkenes. This oxidative transformation proceeds via electrochemical generation of an electrophilic adduct between thianthrene and the alkene substrates. Treatment of these adducts with aliphatic amine nucleophiles and base provides allylic amine products in high yield. This synthetic strategy is also amenable to functionalization of feedstock gaseous alkenes at 1 atm. In the case of 1-butene, high Z-selective crotylation is observed. This strategy, however, is not limited to the synthesis of simple building blocks; complex biologically active molecules are suitable as both alkene and amine coupling partners. Preliminary mechanistic studies implicate vinylthianthrenium salts as key reactive intermediates.

Directing-group-free catalytic dicarbofunctionalization of unactivated alkenes

In the absence of directing auxiliaries, the catalytic addition of carbogenic groups to unactivated alkenes with control of regioselectivity remains an ongoing challenge in organic chemistry. Here we describe a directing-group-free, nickel-catalysed strategy that couples a broad array of unactivated and activated olefins with aryl-substituted triflates and organometallic nucleophiles to afford diarylation adducts in either regioisomeric form, in up to 93% yield and >98% site selectivity. By switching the reagents involved, the present strategy may be extended to other classes of dicarbofunctionalization reactions. Mechanistic and computational investigations offer insights into the origin of the observed regiochemical outcome and the utility of the method is highlighted through the concise syntheses of biologically active molecules. The catalyst control principles reported are expected to advance efforts towards the development of general site-selective alkene functionalizations, removing the requirement for neighbouring activating groups.

Visible-light-driven semihydrogenation of alkynes via proton reduction over carbon nitride supported nickel

Semihydrogenation of alkynes represents one of the most viable route to produce functional alkene products. Herein we describe the visible-light-driven alcohol or water donating semihydrogenation catalyzed by nickel supported on carbon nitride scaffold (Ni/C3N4) under ambient condition, exhibiting excellent alkene selectivity and broad substrate scope. The catalyst design takes advantage of C3N4 to harvest visible irradiation and to tune the interaction of Ni with hydrogenation intermediates, which is essential for the excellent selectivity toward alkene products. The hydrogen atom incorporated in alkene products originates from hydroxyl group of methanol or water, via a Ni catalyzed proton reduction by photogenerated electrons to give the active surface hydrogen species (H*). Such hydrogenation pathway not only avoids harsh reaction condition but also enables facile synthesis of valuable deuterated alkenes using deuterated alcohols or D2O, promising enormous application potential for well-designed catalyst architectures in the light-driven selective transfer hydrogenation (deuteration) of alkynes and other organic substrates.

Recent Advances in Mono‐ and Difunctionalization of Unactivated Olefins

AbstractOlefins are synthetically useful building blocks in modern organic synthesis. Direct functionalization of olefins; represent one of the most explored transformations in synthetic chemistry due to their easy availability and reactivity towards large number of reactants affording diverse range of organic compounds. In recent times, the development of new protocols for the functionalization of olefins is a growing realm. A plethora of olefin functionalization methodologies have been reported in the literature through ionic and free radical mechanisms including single electron transfer (SET) in the last two decades. This review gives an overview of mono‐ and difunctionalization of unactivated olefins, with an emphasis on the mechanistic details.