Tetrasubstituted Alkenes Research Articles

Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products.

Triterpenoid natural products from the Schisandraceae family have long presented a significant synthetic challenge. Lancifodilactone I, a member of the family not previously synthesized, was identified as a key natural product target, from which many other members could be synthesized. We envisaged that the core ring system of lancifodilactone I could be accessed by a strategy involving palladium-catalysed cascade cyclisation of a bromoenynamide, via carbopalladation, Suzuki coupling and 8π-electrocyclisation, to synthesize the core 7,8-fused ring system. Exploration of this strategy on model systems resulted in efficient syntheses of 5,6- and 5,8-fused systems in high yields, which represent the first such cyclisation where the ynamide nitrogen atom is 'external' to the forming ring system. The enamide functionality resident in the cascade cyclisation product was found to be less nucleophilic than the accompanying tri-/tetrasubstituted alkene(s), enabling regioselective oxidations. Application of this strategy to 7,6-, and 7,8-fused systems, and ultimately the 'real' substrate, was ultimately thwarted by the difficulty of 7-membered ring closure, leading to side product formation. Nevertheless, a tandem bromoenynamide carbopalladation, Suzuki coupling and 6/8π-electrocyclisation was shown to be a highly efficient tactic for the formation of bicyclic enamides, which may find applications in other synthetic contexts.

Construction of Chalcogenated Methylene Chroman-3-ones via Palladium-Catalyzed Carbocyclization

We report herein the synthesis of exo-chalcogenated methylene chroman-3-ones via palladium-catalyzed intramolecular acyl-chalcogenation of alkyne with thio- and selenoesters. Chalcogen containing tetrasubstituted alkenes are obtained stereoselectively. This protocol tolerates various functional groups and heterocycles, affording the chroman-3-one products in moderate-to-good yields.

α-Vinylation of Ester Equivalents via Main Group Catalysis for the Construction of Quaternary Centers.

A methodology for the construction of sterically congested quaternary centers via the trapping of vinyl carbocations with silyl ketene acetals is disclosed. This main group-catalyzed α-vinylation reaction is advantageous as methods to access these congested motifs are limited. Moreover, β,γ-unsaturated carbonyl moieties and tetrasubstituted alkenes are present in various bioactive natural products and pharmaceuticals, and this catalytic platform offers a means of accessing them using simple and inexpensive materials.

Paired Oxidative and Reductive Catalysis: Breaking the Potential Barrier of Electrochemical C(sp3)-H Alkenylation.

Due to the intrinsic inertness of alkanes, strong oxidative conditions are typically required to enable their C(sp3)-H functionalization. Herein, a paired electrocatalysis strategy was developed by integrating oxidative catalysis with reductive catalysis in one cell without interference, in which earth-abundant iron and nickel are employed as the anodic and cathodic catalysts, respectively. This approach lowers the previously high oxidation potential required for alkane activation, enabling electrochemical alkane functionalization at the ultra-low oxidation potential of ~0.25 Vvs. Ag/AgCl under mild conditions. Structurally diverse alkenes, including challenging all-carbon tetrasubstituted olefins, can be accessed using readily available alkenyl electrophiles.

Reaction of heteroarenes and 3-alkenyl oxindoles: Synthesis of stereodefined tetrasubstituted alkenes

A novel protocol mediated by DBU for the construction of sp2 C–N bond between 3-alkenyl oxindoles and indazole/benzotriazole has been successfully accomplished. But the cascade reaction of 3-alkenyl oxindoles with benzimidazole leads to the formation of sp2 C-C coupling products under similar conditions. Starting from 3-alkenyl oxindoles, various stereodefined aromatic substituted 3-alkenyl oxindoles can be obtained under simple conditions without contamination by transition-metal residues.

Synthesis of tetra-substituted olefins by NiH-catalyzed hydroacylation of allenes

In this issue of Chem Catalysis, Cho and co-workers invent an innovative way to easily synthesize all-carbon tetra-substituted olefins through a regio- and stereoselective hydroacylation of both 1,1-disubstituted symmetric and unsymmetrical allenes with various anhydrides. This PˆN ligand-ligated NiH system reveals a complementary regioselectivity to Cu catalysis.

Site-selective Hydrogenation/Deuteration of Benzylic Olefins Enabled by Electroreduction Using Water.

We describe an operationally simple and user-friendly protocol that allows the site-selective hydrogenation and deuteration of di-, tri- and tetrasubstituted benzylic olefins by electroreduction while other groups prone to hydrogenation are present. The radical anionic intermediates react with the most inexpensive hydrogen/deuterium source H2 O/D2 O. Our method overcomes many limitations that arise from previously reported electroreductive hydrogenations. The applicability of this reaction is demonstrated by a broad substrate scope (>50 examples) that focuses on functional group tolerance and sites that are affected by metal-catalyzed hydrogenation (alkenes, alkynes, protecting groups).

Integrating Regioselective E→Z Isomerization of Trienones with Cascade Sequences under Photosensitizer-Free Direct Irradiation at 390 nm.

The regioselective E→Z isomerization of a target olefin unit embedded in a conjugated polyene is challenging. Examples are limited to retinal and its derivatives only. The problem is further amplified when such an isomerization is integrated into cascade sequences, among which the regioselectivity and subsequent directionality are the major bottlenecks. Indeed, there are no reports till date for such a transformation. Herein, it is reported that such a controlled isomerization and subsequent cyclization cascade can be enabled by photosensitizer-free direct irradiation of linearly conjugated acyclic polyenes in dichloromethane solvent using a 390 nm LED. The directionality results from deconjugation of the extended π-system in the transient Z-isomer due to stabilizing n→π* interactions between 1,4-dicarbonyls (C=O→C=O) or 1,4-carbonyl/-aryl (C=O→aryl) groups. The involvement of such noncovalent interactions has been supported by X-ray crystallography and control experiments. Thus, conjugated trienones can be stereoselectively converted into oxabicyclo[3.2.1]octadienes in an atom- and step-economic manner, including the first example by regioselective isomerization of a tetrasubstituted alkene. The reaction conditions are very general (>46 examples). The reaction can be conducted under open air atmosphere at ambient temperature. Such a cascade cyclization can also be realized in solid state.

Base-free NiH-catalyzed regio- and stereo-selective hydroacylation of allenes: A new route to synthesis of tetra-substituted olefins

Base-free NiH-catalyzed regio- and stereo-selective hydroacylation of allenes: A new route to synthesis of tetra-substituted olefins

Copper-Catalyzed Radical Addition of Alkynols to Synthesize Difluoroheterocyclic Compounds

A convenient method for the synthesis of fluorine-containing heterocyclic compounds was developed by a copper-catalyzed free radical addition reaction of alkynol and ethyl bromodifluoroacetate. This strategy involves copper-catalyzed free radical addition and molecular lactone exchange of ethynyl alcohol and ethyl bromodifluoroacetate. The method is characterized by easy availability of raw materials, good stereochemical selectivity, and simple operation. More importantly, valuable tetrasubstituted E-configurated alkenes and various vinyl C-Br bonds and difluoromethylene-containing functionalized heterocycles can be obtained by this method.

Lithium Aluminium Hydride and Metallic Iron: A Powerful Team in Alkene and Arene Hydrogenation Catalysis.

Alkenes that normally do not react with LiAlH4 (3-hexene, cyclohexene, 1-Me-cyclohexene), can be reduced to the corresponding alkanes by a mixture of LiAlH4 and Fe0 (the iron was activated by Metal-Vapour-Synthesis). This alkene-to-alkane conversion with a stoichiometric quantity of LiAlH4 /Fe0 does not need quenching with water or acids, implying that both H's originate from LiAlH4 . The LiAlH4 /Fe0 combination is also a remarkably potent cooperative catalyst for hydrogenation of multi-substituted alkenes and benzene or toluene. An induction period of circa two hours and the minimally required temperature of 120 °C, suggests that the actual catalyst is a combination of Fe0 and the decomposition product of LiAlH4 (LiH and Al0 ). A thermally pre-activated LiAlH4 /Fe0 catalyst did not need an induction time and is also active at room temperature and 1 bar H2 . A combination of AliBu3 and Fe0 is an even more active hydrogenation catalyst. Without pre-activation, tetra-substituted alkenes like Me2 C=CMe2 and toluene could be fully hydrogenated.

Stereoselective Synthesis of Tetraarylethylenes Enabled by Reductive anti-1,2-Dimetallation of Alkynes.

Tetraarylethylenes (TAEs) have been gaining attention from various scientific disciplines for their characteristic chemical and physical properties. From the synthetic perspective, however, efficient methods for the selective synthesis of different isomers of TAEs are still underdeveloped. Here, we report the regio- and stereoselective synthesis of TAEs by means of sodium-promoted reductive anti-1,2-dimagnesiation of alkynes. Subsequent transmetallation to zinc generates trans-1,2-dizincioalkenes, which underwent the stereoselective arylation under a palladium catalysis to afford a variety of TAEs that had been difficult to prepare according to the conventional procedures. In addition, the present method accommodates not only diarylacetylenes but also alkyl aryl acetylenes and thus enables to synthesize a wide range of all-carbon tetrasubstituted alkenes.

Nickel-Catalyzed Unsymmetrical Bis-Allylation of Alkynes.

The catalytic bis-allylation of alkynes is an important but challenging protocol to construct all-carbon tetra-substituted alkenes. Particularly, the catalytic unsymmetrical bis-allylation of alkynes remains as an underexplored task to date. We herein report an unprecedented unsymmetrical bis-allylation by simultaneously utilizing electrophilic trifluoromethyl alkene and nucleophilic allylboronate as the allylic reagents. With the aid of robust Ni0 /NHC catalysis, valuable skipped trienes can be obtained in high regio- and stereo-selectivities under mild conditions. Mechanistic studies indicate that the reaction may proceed through a β-fluorine elimination of a nickelacycle followed by a transmetalation step with allylboronate. The present method exhibits a good tolerance of various functional groups. Besides, the skipped triene products can undergo an array of elaborate transformations, which highlights the potential applications of this strategy.

Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2-Substituted Cyclopentyl Aryl Ketones

Asymmetric hydrogenation of tetrasubstituted alkenes is an important but challenging research topic. Herein, we report an efficient iridium-catalyzed asymmetric hydrogenation of tetrasubstituted α,β-unsaturated ketones for the synthesis of chiral 2-substituted cyclopentyl aryl ketones, an important chiral structural motif for the preparation of chiral pharmaceuticals and bioactive molecules. The reaction proceeded very well with good functional group compatibility and delivered the hydrogenated products in high yields and stereoselectivities (up to 99% yield, >20:1 dr and 99% ee). In addition, the reaction could be carried out on a gram-scale, and all four stereoisomers of the hydrogenated products bearing two contiguous stereocenters were obtained. Furthermore, the hydrogenated product can be transformed into the ERβ agonist Erteberel, and the reaction pathway was also studied via deuterium-labelling experiments.

Three Component syn-1,2-Arylmethylation of Internal Alkynes.

A Pd-catalyzed three-component syn-1,2-arylmethylation of internal alkynes (ynamides/yne-acetates/alkynes) is described. The readily available and bench stable coupling partners iodo-arenes, and methyl boronic acid are successfully used in this coupling strategy to access the methyl-containing tetra-substituted olefins; the scope is broad showing excellent functional-group tolerance. Notably, the transformation is regio- as well as stereoselective. The biologically relevant motifs (BRM) bearing iodo-arenes and ynamides are also used for the late-stage syn-1,2-arylmethylation of alkynes. Aryl-alkylation, aryl-trideuteriomethylation, alkynyl-methylation, and alkenyl-methylation of ynamides are also presented. The Me-substituted alkenes are further transformed into synthetically important β-amino-indenones and α-fluoro-α'-methyl ketones.

Modular assembly of versatile tetrasubstituted alkenyl monohalides from alkynyl tetracoordinate borons

•Success of two different novel migration modes from alkynyl tetracoordinate borons •Modular synthesis of valuable and versatile tetrasubstituted alkenyl monohalides •Construction of various other types tetrasubstituted olefins from such compounds •Toleration with complex natural products or therapeutical agents Tetrasubstituted olefins as a pivotal scaffold have been extensively employed in pharmaceuticals, natural products, polymer chemistry, and material sciences and arouse great attention in chemical community. Despite advances on the assembly of fully carbon tetrasubstituted olefins, the synthesis of tetrasubstituted alkenyl monohalides are underdeveloped and elusive. Herein, we report four intriguing migration reactions from alkynyl tetracoordinate boron species, in which various common, inexpensive, and user-friendly halogen electrophiles (Selectfluoro, TCCA, NIS, and NBS) are suitable electrophilic halogen sources. Versatile tetrasubstituted olefins were thus readily accessible from transition-metal-catalyzed transformations of these newly built tetrasubstituted alkenyl monohalides under suitable reaction conditions. The mechanistic investigations suggest that different electrophilic halogen sources promote different aryl migration routes of alkynyl tetracoordinate boron species, rendering various tetrasubstituted alkenyl monohalides, respectively. Distinct reaction modes, unusual mechanism, valuable products, and versatile transformations portray the advantages and significance of our protocol. Tetrasubstituted olefins as a pivotal scaffold have been extensively employed in pharmaceuticals, natural products, polymer chemistry, and material sciences and arouse great attention in chemical community. Despite advances on the assembly of fully carbon tetrasubstituted olefins, the synthesis of tetrasubstituted alkenyl monohalides are underdeveloped and elusive. Herein, we report four intriguing migration reactions from alkynyl tetracoordinate boron species, in which various common, inexpensive, and user-friendly halogen electrophiles (Selectfluoro, TCCA, NIS, and NBS) are suitable electrophilic halogen sources. Versatile tetrasubstituted olefins were thus readily accessible from transition-metal-catalyzed transformations of these newly built tetrasubstituted alkenyl monohalides under suitable reaction conditions. The mechanistic investigations suggest that different electrophilic halogen sources promote different aryl migration routes of alkynyl tetracoordinate boron species, rendering various tetrasubstituted alkenyl monohalides, respectively. Distinct reaction modes, unusual mechanism, valuable products, and versatile transformations portray the advantages and significance of our protocol.

Butterflyene: an entry into an aesthetically pleasing carbocycle via a Diels-Alder reaction on a tetrasubstituted olefin.

An interesting molecular architecture, butterflyene, resembling the shape of a butterfly has been synthesized via a sequence of cyclocondensation, benzylic oxidation, McMurry coupling and Diels-Alder reaction (DAR), successively. The DAR of the tetrasubstituted double bond of a bicyclopentylidene moiety with various dienes has been performed to prepare the analogues of butterflyene. DFT calculations have also been used to analyze the structural optimization and reaction energies.

Light-mediated sulfonyl-iodination of ynamides and internal alkynes.

We synthesized tetrasubstituted olefins regioselectively and stereoselectively from ynamides and internal alkynes with sulfonyl iodides under blue LEDs in few minutes. The key features are being metal-free, easy to handle, simple, broad in scope, and environmentally friendly. Furthermore, a gram-scale experiment was conducted, and the synthesized corresponding sulfonyl-iodinated products were smoothly altered into various other products.

Construction of the [7–5–5] Tricyclic Core of Daphniphyllum Alkaloids via a Cationic Cascade Reaction

The [7-5-5] tricyclic core of daphniphyllum alkaloids, containing contiguous stereogenic centers at C14 and C15 and a tetrasubstituted alkene moiety between C9 and C10, was constructed via a cascade reaction that involved an electrocyclic reaction of a pentadienyl cation and intramolecular interception of the resultant cyclopentenyl cation.

Diboration of Alkynes Accelerated by Synergistic Effects of Ruthenium Complexes and Phenoxides

AbstractAlkynes react with bis(pinacolato)diboron (B2pin2) in the presence of 5–10 mol % [Cp*RuCl2]n to afford the corresponding (Z)‐1,2‐diboryl alkenes. The addition of 30 mol % NaOC6H4(4‐tBu) and 2–5 equiv. of methanol was essential for the reaction to proceed with high product yield. Various alkynes were employed in the reaction, and the obtained 1,2‐diboryl alkenes were used as precursors for tetrasubstituted alkenes.