Terminal Alkenes Research Articles

Ambient Pressure Hydroformylation – A Key Step to Meso‐Alkyl BODIPYs

AbstractHerein, a highly efficient five‐step reaction sequence to meso‐alkyl BODIPYs is presented. In our previous work, the hydroformylation of terminal alkenes was used to generate an aldehyde from an alkene via rhodium catalysis and use them in a subsequent tandem reaction to obtain BODIPY dyes. However, the use of higher pressures and therefore autoclaves as well as their necessary equipment might limit others to use this method. The refined approach in this work employs ambient pressure hydroformylation, done in a simple Schlenk tube and using a CO/H2 balloon, as key step towards an easier meso‐alkyl BODIPY synthesis. Additionally, the use of MTBE instead of chloroform as reaction solvent results in a greener approach. Readily available and easily synthesizable alkenes as well as different pyrrole building blocks can be used to extend the range of known alkyl‐BODIPYs. The synthesis of 23 derivatives with overall yields of up to 67 % demonstrates the wide applicability and advantages of the refined method.

Photoinduced Pd‐Catalyzed Direct Sulfonylation of Allylic C−H Bonds

AbstractAllylic sulfones are valuable motifs due to their medicinal and biological significance and their versatile chemical reactivities. While direct allylic C−H sulfonylation represents a straightforward and desirable approach, these methods are primarily restricted to terminal alkenes, leaving the engagement of the internal counterparts a formidable challenge. Herein we report a photocatalytic approach that accommodates both cyclic and acyclic internal alkenes with diverse substitution patterns and electronic properties. Importantly, the obtained allylic sulfones can be readily diversified into a wide range of products, thus enabling formal alkene transposition and all‐carbon quaternary center formation through the sequential C−H functionalization.

Platinum‐Catalyzed Regio‐ and Enantioselective Diboration of Unactivated Alkenes with (pin)B−B(dan)

AbstractAsymmetric diboration of terminal alkenes is well established, and subsequent selective functionalization of the less hindered primary boronic ester is commonly achieved. Conversely, selective functionalization of the sterically less accessible secondary boronic ester remains challenging. An alternative way to control chemoselective functionalization of bis(boron) compounds is by engendering different Lewis acidity to the two boryl moieties, since reactivity would then be dictated by Lewis acidity instead of sterics. We report herein the regio‐ and enantioselective Pt‐catalyzed diboration of unactivated alkenes with (pin)B−B(dan). A broad range of terminal and cyclic alkenes undergo diboration to furnish the differentiable 1,2‐bis(boron) compounds with high levels of regio‐ and enantiocontrol, giving access to a wide variety of novel building blocks from a common intermediate. The reaction places the less Lewis acidic B(dan) group at the less hindered position and the resulting 1,2‐bisboryl alkanes undergo selective transformations of the B(pin) group located at the more hindered position. The regioselectivity of the diboration has been studied by DFT calculations and is believed to originate from the trans influence, which lowers the activation barrier for formation of the regioisomer that places the weaker electron donor [B(pin) vs B(dan)] opposite the strong electron donor (alkyl group) in the platinum complex.

Efficient construction of a quinoline framework from alcohols, nitroarenes, and alkenes promoted by a trimetallic catalyst system

A Pd/Fe/In-trimetallic catalyst system promotes the three-component coupling reaction of primary alcohols, nitroarenes, and terminal alkenes to construct quinoline frameworks in a single operation. These consecutive coupling reactions proceed via an oxidative Povarov reaction of alkenes and aldimines derived from primary alcohols and nitroarenes by a redox hydrogen transfer system. This reaction may contribute to the efficient development of pharmaceuticals and medicinal products.

Site Specific C3‐Alkenylation of Indoles Mediated by in situ C‐H Iodination

Text. The C3‐alkenylation of indoles have been developed by means of a novel in situ iodination tactic which is capable of mediating the Heck coupling with alkenes. The method features specific site‐selectivity oriented by the C‐I bond, high‐step efficiency without pre‐functionalization for C‐halogen bond construction, as well as the highly general tolerance to different terminal alkenes, including unactivated alkenes, acrylates, acrylic acid, vinyl sulfone as well as different vinyl functionalized natural products.

Hydrocarboxylation of Terminal Alkenes with Formate by a ZnIn2S4 Photocatalyst

Hydrocarboxylation of Terminal Alkenes with Formate by a ZnIn2S4 Photocatalyst

Photoredox Catalyzed Tandem Denitrogenative [4 + 2] Annulation of 1,2,3-Benzotriazin-4(3H)-ones with Terminal Olefins.

The dihydroisoquinolones skeleton is ubiquitous in natural products and biological molecules. Reported strategies for constructing dihydroisoquinolones usually require noble metal catalysts or stoichiometric oxidants, which limit their wide applications. Herein, we developed a photoredox catalyzed tandem denitrogenative [4 + 2] annulation reaction of 1,2,3-benzotriazin-4(3H)-ones with terminal olefins. A variety of dihydroisoquinolones can be accessed in moderate to excellent yield. This protocol features high atom-economy, mild reaction conditions, and is external oxidant-free, enabling the synthesis of various substituted dihydroisoquinolones.

Multifunctional Polymer Synthesis via Sequential Postpolymerization Modification Using a Single Aldehyde Repeat Unit: Allylation and Orthogonal Esterification and Thiol-ene Reaction.

Herein, we present a highly efficient method for synthesizing multifunctional polymers. This method involves the sequential postpolymerization modification (PPM) of a highly reactive aldehyde polymer. We introduce an allylic alcohol functionality into the polymer backbone via Barbier-type allylation, a process facilitated by easy-to-handle indium(0) powder. This step enables the formation of orthogonal pendants, secondary alcohol, and terminal alkene, which can be further functionalized through esterification and thiol-ene click reactions. All of these processes are carried out under mild conditions, ensuring high efficiency and a wide range of functional groups. Our study underscores PPM's operational simplicity and versatility in developing advanced polymer materials and expanding the scope of multifunctional polymer design.

Unlocking Oxetane Potential: Modular Synthetic Platform for the Concise Synthesis of Acyclic Oligo-Isoprenoids and Terpenoids.

Terpenes occupy a unique place among the secondary metabolites due to their broad utility and extraordinary structural diversity. Their synthesis via polyene cyclization, either biomimetic or enzymatic, represents the cutting edge of modern synthetic chemistry. However, these endeavors have been inherently tied to the availability of natural and non-natural acyclic polyene starting materials. Herein, we report an oxetane-based platform for the modular construction of oxygenated polyolefins with precise geometric control. This "tail-to head" iterative method leverages the site-selective cross-metathesis of terminal olefins to form an alkylidene oxetane moiety and the regioselective ring opening of alkenyl-oxetanes for chain elongation. In addition, the unique and peculiar propensity of alkylidene oxetane fragment in various reactions was also revealed and exploited for site-selective functionalization, cyclization, and as a protecting group in polyenes.

Photoinduced Pd-Catalyzed Direct Sulfonylation of Allylic C-H Bonds.

Allylic sulfones are valuable motifs due to their medicinal and biological significance and their versatile chemical reactivities. While direct allylic C-H sulfonylation represents a straightforward and desirable approach, these methods are primarily restricted to terminal alkenes, leaving the engagement of the internal counterparts a formidable challenge. Herein we report a photocatalytic approach that accommodates both cyclic and acyclic internal alkenes with diverse substitution patterns and electronic properties. Importantly, the obtained allylic sulfones can be readily diversified into a wide range of products, thus enabling formal alkene transposition and all-carbon quaternary center formation through the sequential C-H functionalization.

Defluorinative Haloalkylation of Unactivated Alkenes Enabled by Dual Photoredox and Copper Catalysis.

A three-component defluorinative haloalkylation of alkenes with trifluoromethyl compounds and TBAX (X = Cl, Br) via dual photoredox/copper catalysis is reported. The mild conditions are compatible with a wide array of activated trifluoromethyl aromatics bearing diverse substituents, and various nonactivated terminal and internal alkenes, enabling straightforward access to synthetically valuable γ-gem-difluoroalkyl halides with high efficiency. Mechanistic studies indicate that the [Cu] complexes not only serve as XAT catalysts but also facilitate the SET reduction of trifluoromethyl groups by photocatalysts. Additionally, the resulting alkyl halide products can serve as versatile conversion intermediates for the synthesis of a diverse range of γ-gem-difluoroalkyl compounds.

Alkene Isomerization Catalyzed by a Mn(I) Bisphosphine Borohydride Complex.

An additive-free manganese-catalyzed isomerization of terminal alkenes to internal alkenes is described. This reaction is implementing an inexpensive nonprecious metal catalyst. The most efficient catalyst is the borohydride complex cis-[Mn(dippe)(CO)2(κ2-BH4)]. This catalyst operates at room temperature, with a catalyst loading of 2.5 mol %. A variety of terminal alkenes is effectively and selectively transformed into the respective internal E-alkenes. Preliminary results show chain-walking isomerization at an elevated temperature. Mechanistic studies were carried out, including stoichiometric reactions and in situ NMR analysis. These experiments are flanked by computational studies. Based on these, the catalytic process is initiated by the liberation of "BH3" as a THF adduct. The catalytic process is initiated by double bond insertion into an M-H species, leading to an alkyl metal intermediate, followed by β-hydride elimination at the opposite position to afford the isomerization product.

Photocatalytic Multisite Functionalization of Unactivated Terminal Alkenes by Merging Polar Cycloaddition and Radical Ring-Opening Process.

Although highly appealing for rapid access of molecular complexity, multi-functionalization of alkenes that allows incorporation of more than two functional groups remains a prominent challenge. Herein, we report a novel strategy that merges dipolar cycloaddition with photoredox promoted radical ring-opening remote C(sp3)-H functionalization, thus enabling a smooth 1,2,5-trifunctionalization of unactivated alkenes. A highly regioselective [3+2] cycloaddition anchors a reaction trigger onto alkene substrates. The subsequent halogen atom transfer (XAT) selectively initiates ring-opening process, which is followed by a series of 1,5-hydrogen atom transfer (1,5-HAT) and intermolecular fluorine atom transfer (FAT) events. With this method, site-selective introduction of three different functional groups is accomplished and a broad spectrum of valuable β-hydroxyl-ϵ-fluoro-nitrile products are synthesized from readily available terminal alkenes.

Photocatalytic Multisite Functionalization of Unactivated Terminal Alkenes by Merging Polar Cycloaddition and Radical Ring‐Opening Process

AbstractAlthough highly appealing for rapid access of molecular complexity, multi‐functionalization of alkenes that allows incorporation of more than two functional groups remains a prominent challenge. Herein, we report a novel strategy that merges dipolar cycloaddition with photoredox promoted radical ring‐opening remote C(sp3)−H functionalization, thus enabling a smooth 1,2,5‐trifunctionalization of unactivated alkenes. A highly regioselective [3+2] cycloaddition anchors a reaction trigger onto alkene substrates. The subsequent halogen atom transfer (XAT) selectively initiates ring‐opening process, which is followed by a series of 1,5‐hydrogen atom transfer (1,5‐HAT) and intermolecular fluorine atom transfer (FAT) events. With this method, site‐selective introduction of three different functional groups is accomplished and a broad spectrum of valuable β‐hydroxyl‐ϵ‐fluoro‐nitrile products are synthesized from readily available terminal alkenes.

Effect of Carbon Chain Length on Nascent Yields of Stabilized Criegee Intermediates in Ozonolysis of a Series of Terminal Alkenes.

The yields of stabilized Criegee intermediates (sCIs), CH2OO and RCHOO (C2H5CHOO, C3H7CHOO, C4H9CHOO, and C5H11CHOO), produced from ozonolysis of asymmetrical 1-alkenes (1-butene, 1-pentene, 1-hexene, and 1-heptene) were investigated at low pressures (5-16 Torr) using cavity ring-down spectroscopy and chemical titration with sulfur dioxide (SO2). By extrapolating the low-pressure measurements to zero-pressure limit, nascent sCI yields were obtained. Combined with our previous studies on ethene and propene ozonolysis, the nascent sCI yields demonstrated an intriguing trend of increasing with the addition of CH2 groups and eventually reached a plateau at around 31% for longer chain 1-alkenes. In particular, the fraction of nascent stabilized CH2OO reached the plateau from 1-butene, indicating that CH2OO was produced with nearly the same internal energy distribution from 1-butene to 1-heptene. The comparison between the experiments and RRKM calculations suggests that the dissociation of primary ozonide (POZ) of O3 + ethene and propene can be treated by statistical theory, while that of O3 + 1-butene to 1-heptene is nonstatistical and intramolecular vibrational redistribution of the initial energy on the 1,2,3-trioxolane of POZ throughout the entire molecule was incomplete on the dissociation time scale.

Synthesis of non-canonical amino acids through dehydrogenative tailoring.

Amino acids are essential building blocks in biology and chemistry. Whereas nature relies on a small number of amino acid structures, chemists desire access to a vast range of structurally diverse analogues1-3. The selective modification of amino acid side-chain residues represents an efficient strategy to access non-canonical derivatives of value in chemistry and biology. While semisynthetic methods leveraging the functional groups found in polar and aromatic amino acids have been extensively explored, highly selective and general approaches to transform unactivated C-H bonds in aliphatic amino acids remain less developed4,5. Here we disclose a stepwise dehydrogenative method to convert aliphatic amino acids into structurally diverse analogues. The key to the success of this approach lies in the development of a selective catalytic acceptorless dehydrogenation method driven by photochemical irradiation, which provides access to terminal alkene intermediates for downstream functionalization. Overall, this strategy enables the rapid synthesis of new amino acid building blocks and suggests possibilities for the late-stage modification of more complex oligopeptides.

Platinum-Catalyzed Regio- and Enantioselective Diboration of Unactivated Alkenes with (pin)B-B(dan).

Asymmetric diboration of terminal alkenes is well established, and subsequent selective functionalization of the less hindered primary boronic ester is commonly achieved. Conversely, selective functionalization of the sterically less accessible secondary boronic ester remains challenging. An alternative way to control chemoselective functionalization of bis(boron) compounds is by engendering different Lewis acidity to the two boryl moieties, since reactivity would then be dictated by Lewis acidity instead of sterics. We report herein the regio- and enantioselective Pt-catalyzed diboration of unactivated alkenes with (pin)B-B(dan). A broad range of terminal and cyclic alkenes undergo diboration to furnish the differentiable 1,2-bis(boron) compounds with high levels of regio- and enantiocontrol, giving access to a wide variety of novel building blocks from a common intermediate. The reaction places the less Lewis acidic B(dan) group at the less hindered position and the resulting 1,2-bisboryl alkanes undergo selective transformations of the B(pin) group located at the more hindered position. The regioselectivity of the diboration has been studied by DFT calculations and is believed to originate from the trans influence, which lowers the activation barrier for formation of the regioisomer that places the weaker electron donor [B(pin) vs B(dan)] opposite the strong electron donor (alkyl group) in the platinum complex.

Review of recent development in Anti-Markovnikov addition reaction of olefins

The regioselective functionalization of terminal olefins is of significant importance in organic synthesis. Based on the critical observations of Markovnikov, the types of addition products can be identified as Markovnikov or anti-Markovnikov products. In recent years, the anti-Markovnikov addition reaction of olefins has caught many scientists’ eyes because of its broad application prospects in chemical and pharmaceutical industries and its perfectly compliant with green chemistry. Herein, we summarized the main methodologies developed for the functionalization of olefins and compared their advantages and disadvantages, hoping that this minireview can provide some inspiration for researchers to develop more effective pathways of functional group production based on olefins.

Alkene Isomerisation Catalysed by a Superbasic Sodium Amide.

Typically catalysed by transition metals, alkene isomerisation is a powerful methodology for preparation of internal olefins. In contrast, the use of more earth abundant main group reagents is limited to activated substrates, requiring high temperatures and excess stoichiometric amounts. Opening a new avenue for progressing this field, here we report applications of bulky sodium amide NaTMP (TMP=2,2,6,6-tetramethylpiperidide) when partnered with tridentate Lewis donor PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine) in catalytic alkene isomerisation of terminal olefins under mild reaction conditions. An array of distinct olefins could successfully be isomerised, including unactivated olefins, allylamines, and allylethers, showing the high activity of this partnership. In-depth mechanistic insights provided by X-ray crystallography, real-time nuclear magnetic resonance (NMR) monitoring, and density functional theory (DFT) calculations have unveiled the crucial role of in situ-generated TMP(H) in facilitating efficient isomerisation, and the choice of alkali-metal. Additionally, theoretical studies shed light on the observed E/Z selectivity, particularly accounting for the selective formation of Z-vinyl ethers. The versatility of our method is further demonstrated through the isomerisation of unactivated cycloalkenes, which undergo hydrogen isotope exchange to produce deuterated compounds.

Alkene Isomerisation Catalysed by a Superbasic Sodium Amide

AbstractTypically catalysed by transition metals, alkene isomerisation is a powerful methodology for preparation of internal olefins. In contrast, the use of more earth abundant main group reagents is limited to activated substrates, requiring high temperatures and excess stoichiometric amounts. Opening a new avenue for progressing this field, here we report applications of bulky sodium amide NaTMP (TMP=2,2,6,6‐tetramethylpiperidide) when partnered with tridentate Lewis donor PMDETA (N,N,N′,N′′,N’’‐pentamethyldiethylenetriamine) in catalytic alkene isomerisation of terminal olefins under mild reaction conditions. An array of distinct olefins could successfully be isomerised, including unactivated olefins, allylamines, and allylethers, showing the high activity of this partnership. In‐depth mechanistic insights provided by X‐ray crystallography, real‐time nuclear magnetic resonance (NMR) monitoring, and density functional theory (DFT) calculations have unveiled the crucial role of in situ‐generated TMP(H) in facilitating efficient isomerisation, and the choice of alkali‐metal. Additionally, theoretical studies shed light on the observed E/Z selectivity, particularly accounting for the selective formation of Z‐vinyl ethers. The versatility of our method is further demonstrated through the isomerisation of unactivated cycloalkenes, which undergo hydrogen isotope exchange to produce deuterated compounds.