Terminal Alkenes Research Articles

Carboazidation of Terminal Alkenes with Trimethylsilyl Azide and Cyclic Ethers Catalyzed by Copper Powder under Oxidative Conditions.

Copper-catalyzed carboazidation of alkenes with trimethylsilyl azide and cyclic ethers has been achieved. The employment of naturally abundant copper catalysts allowed cyclic ethers to be used as alkylating reagents under oxidative conditions. The use of styrene derivatives and 1,1-diaryl alkenes afforded carboazidation products. In addition, application of five- and six-membered cyclic ethers to the present reaction gave target organic molecules bearing azide and cyclic ether groups with perfect regioselectivity. Radical trapping and clock experiments revealed that the present reaction proceeded via the radical pathway. To further demonstrate the utility of this carboazidation reaction, transformations from the azide group to the related nitrogen-containing compounds were also performed.

Iron-Catalyzed Intermolecular Oxyamination of Terminal Alkenes Promoted by HFIP Using Hydroxylamine Derivatives

An atom-economical intermolecular iron-catalyzed oxyamination of alkenes is described herein. The insertion of oxygenated and nitrogenated moieties from the hydroxylamine substrate was observed with full regio- and chemo-selectivity for terminal alkenes in good yields. HFIP as a solvent appeared to have a synergistic effect with the iron catalyst to promote the formation of the oxyaminated products. Preliminary mechanistic studies suggest a pathway going through an aziridination reaction followed by an in situ ring opening.

Styrene Oxide Isomerase-Catalyzed Meinwald Rearrangement in Cascade Biotransformations: Synthesis of Chiral and/or Natural Chemicals.

Styrene oxide isomerase (SOI) catalyzes the Meinwald rearrangement of aryl epoxides to carbonyl compounds via a 1,2-trans-shift in a stereospecific manner. A number of cascade biotransformations with SOI-catalyzed epoxide isomerization as a key step have been developed to convert readily available substrates into valuable chiral chemicals. Cascade conversion of terminal or internal alkenes into chiral acids, alcohols or amines was achieved, which involved SOI-catalyzed enantio-retentive isomerization of terminal epoxides via 1,2-H shift, or internal epoxides via 1,2-methyl shift. SOI-involved cascades were also developed to convert racemic epoxides into chiral acids or amines via dynamic kinetic resolution. Additionally, combining SOI-catalyzed isomerization with enantioselective C-C bond forming enzymes enabled the synthesis of chiral amino acids or amino alcohols from racemic epoxides. Finally, integration of SOI-involved cascades with biosynthesis pathways allowed for the direct utilization of renewable substrates for the sustainable synthesis of high-value natural chemicals such as alcohols, acids, and esters.

Pd-Catalyzed TBHP-Mediated Selective Wacker-Type Oxidation and Oxo-acyloxylation of Olefins Using a 2-(1H-Indazol-1-yl)quinoline Ligand.

Pd(II)-catalyzed oxidation of terminal olefins to methyl ketones has emerged as an attractive strategy for organic synthesis. Here we report the Pd(II)-catalyzed selective oxidation of olefins using tert-butyl hydroperoxide as the oxidant and 2-(1H-indazol-1-yl)quinoline as the ligand. A wide range of olefins were well tolerated in this reaction system to provide methyl ketones, whereas the presence of Ac2O initiated the oxo-acyloxylation to afford the α-acetoxyacetone products. Isotope labeling studies and active-intermediate-capture experiments were performed to elucidate the underlying selective reaction mechanism. Notably, the generation of α-acetoxyacetone products involves the palladium enolate intermediate while the methyl ketone products were generated through the most commonly proposed alkylperoxide intermediates, followed by 1,2-hydride migration.

Synthesis and characterisation of fluorescent substrates for eukaryotic protein N-glycosylation

Herein we report the synthesis of two fluorescently labelled analogues of C25 dolichol (Dol25) in which the terminal isoprene unit has been replaced by a dansyl or 7-amino-4-trifluoromethylcoumarin fluorophore, a transformation enabled by the regioselective epoxidation of the terminal olefin via its bromohydrin using the van Tamelen procedure. The lipid alcohols were phosphorylated and glycosylated to obtain lipid-linked chitobiose-α-diphosphates and a lipid-linked mannosyl-β-phosphate. Biochemical assays showed that these labelled substrates are accepted by eukaryotic protein N-glycosylation enzymes with rates comparable to the unlabelled substrates, reconstituting a major part of the pathway up to the lipid-linked dodeca-saccharide Glc1Man9GlcNAc2-PP-Dol25 and its transfer to an acceptor peptide catalysed by eukaryotic oligosaccharyltransferases (OSTs), namely the single-subunit OST STT3A from Trypanosoma brucei and the octameric OST complex from Saccharomyces cerevisiae. The fluorescent labels facilitate handling and purification of the lipid-linked glycosyl donors and acceptors and should facilitate further biochemical studies of protein glycosylation enzymes.

Stereo-complementary epoxidation of 4-vinyl-2,3-dihydrobenzofuran using mutants of SeStyA with enhanced stability and enantioselectivity

The asymmetric epoxidation of unfunctionalized terminal olefins remains a challenge. Styrene monooxygenase SeStyA from Streptomyces exfoliatus could catalyze the enantioselective epoxidation of terminal olefins. To improve the robustness of SeStyA, a consensus-based approach was applied, which led to the successful identification of several beneficial mutations with enhanced thermostability or enantioselectivity in the epoxidation of 4-vinyl-2,3-dihydrobenzofuran (1a), a Tasimelteon intermediate. After sequential combinatory mutagenesis, mutants M6R and M5S with complementary enantioselectivity were selected to catalyze respectively the (R)- and (S)-epoxidation of 1a, generating both enantiomers with 99% ee. The inactivation half-life of M6R and M5S at 40 °C was increased to 25.4 and 5.9-fold of the wild-type, respectively. Both can catalyze the complete epoxidation of 20 mM substrate within 2 to 3 h, a significant improvement from the 20% conversion of the wild-type. The results were interpreted in the context of the model structure of SeStyA.

Mechanism for the synthesis of medium-chain 1-alkenes from fatty acids catalyzed by binuclear iron UndA decarboxylase

Terminal olefins synthesized by the decarboxylation of fatty acids are important platform chemicals. PfUndA is a nonheme di-iron oxidase capable of converting medium-chain (C10 ∼ C14) fatty acids into the corresponding 1-alkenes. Using density functional theory calculations, it is demonstrated that the PfUndA-catalyzed lauric acid decarboxylation is initiated by introducing one pair of H+/e−. The subsequent reaction mainly involves the O − O bond dissociation, the partial interconversion between active high-spin Fe(III)-O• and inactive medium-spin Fe(IV) = O, the formation of triple-hydroxyl intermediates and substrate Cβ radical resulted from successive hydrogen transfers, the stepwise decarboxylation of substrate radical, and the protonation of Fe-bound hydroxides with H+ and e− added. Other mechanistic possibilities have been excluded. It is further found that the low catalytic efficiency of UndA may be due to the energy penalty caused by the drop of active high-spin Fe(III)-O• to a deeper minimum (inert medium-spin Fe(IV) = O).

Lewis Acid-Catalyzed Remote Site-Selective Ring Deconstruction of Cyclobuteno[a]naphthalene-4-ones to Access Unsymmetric 1,1-Diarylated Olefins.

A catalytic site-selective ring deconstruction of cyclobuteno[a]naphthalene-4-ones with alcohols is reported, enabling the direct production of a wide range of unsymmetric 1,1-diarylated olefins with good yields and complete regioselectivity. The late-stage application of these resulting terminal olefins demonstrates great possibilities to apply this strategy to complex molecules. The protocol features good functional group compatibility, broad substrate scope, and controllable site selectivity.

Pd-PEPPSI complexes in water: Synthesis of (E)-2-(styryl)pyridines via Heck coupling reaction and screening of the optoelectronicproperties

A series of Pd-N-heterocyclic carbenes, i.e., palladium-pyridine enhanced pre-catalyst preparation stabilization and initiation (Pd-PEPPSI) complexes, were synthesized and tested their catalytic efficiency in our previous works towards C2-arylation, C-C and C-heteroatom bond formation reactions. Herein, we wish to extend our research studies to synthesizing styryl pyridines via Heck coupling reactions (HCR) and oxidative Heck coupling reactions (OHCR). In the current report, we have developed a method in two different routes; method i represents HCR; it involves terminal alkenes and aryl halides in the presence of a base and Pd-PEPPSI complexes in H2O. In method ii, the reaction undergoes between aryl boronic acids, terminal alkenes, oxidant and Pd-PEPPSI catalyst, i.e., OHCR. Our results revealed that the boronic acids gave superior yields over aryl halides for the formation of styryl pyridines without adding any extraneous base. Further, the catalyst can be resumed and reused for three cycles and there is no loss of catalytic activity. It can also be noted that these Pd-PEPPSI complexes might help to reduce the organic waste and avoid hazardous reaction conditions. The prepared styryl pyridine derivatives possess an E-configuration and are structurally confirmed by 1H NMR spectra. We examined the photophysical properties of the prepared compounds of styryl pyridines. The absorption led to identifying the absorption maxima in between 200 and 450 nm, whereas emission spectra demonstrated less intensity shoulder peaks and more intense vibrationally resolved peaks starting from 300 nm to 600 nm.

A Tungsten Oxo Alkylidene Supported on Sulfated Zirconium Oxide for Olefin Metathesis

The reaction of W(O)(Adene)(2,5-dimethylpyrrolide)2 (1; Adene = 2-adamantylidene) and sulfated zirconium oxide (SZO) results in the formation of [W(O)(Adene)(2,5-dimethylpyrrolide)][SZO] (1@SZO). 1@SZO reacts with 13C-labeled ethylene to give 1-13C-adamantylethylene and square pyramidal [W(O)(CH2)3(2,5-dimethylpyrrolide)][SZO] (2) as major reaction products; small amounts of [13C]propene and [W(O)(H2C═CH2)(2,5-dimethylpyrrolide)][SZO] (3) also form in this reaction. 1@SZO is active in olefin metathesis of terminal olefins, including methyl 10-undecenoate, to give the thermodynamic E-olefin product; and also catalyzes the direct formation of propylene from ethylene.

Directed Asymmetric Nickel‐Catalyzed Reductive 1,2‐Diarylation of Electronically Unactivated Alkenes

AbstractTransition‐metal catalyzed intermolecular 1,2‐diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition‐metal catalyzed asymmetric 1,2‐diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel‐catalyzed reductive 1,2‐diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2‐diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni‐catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.

Directed Asymmetric Nickel-Catalyzed Reductive 1,2-Diarylation of Electronically Unactivated Alkenes.

Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel-catalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2-diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.

Origins of Regioselectivity in CuH-Catalyzed Hydrofunctionalization of Alkenes.

Factors controlling the regioselectivity in alkene hydrocupration were computationally investigated using energy decomposition analysis. The results demonstrate that the Markovnikov-selective hydrocupration with electronically activated mono-substituted olefins is mostly affected by the destabilizing Pauli repulsion, which is due to the electron delocalization effect. The anti-Markovnikov-selective hydrocupration with 1,1-dialkyl-substituted terminal olefins is dominated by the repulsive electrostatic interactions, which is because of the unequal π electron distribution caused by the induction effect of alkyl substituents.

Facile Synthesis of β-Tetracyano Vanadyl Porphyrin from Its Tetrabromo Analogue and Its Excellent Catalytic Activity for Bromination and Epoxidation Reactions.

Complex 2,3,12,13-tetracyano-5,10,15,20-tetraphenylporphyrinatooxidovanadium(IV) {[VIVOTPP(CN)4], 2} has been prepared by nucleophilic substitution of β-bromo groups of the corresponding 2,3,12,13-tetrabromo-5,10,15,20-tetraphenylporphyrinatooxidovanadium(IV) {[VIVOTPP(Br)4], 1} using CuCN in quinoline. Both complexes show biomimetic catalytic activity similar to enzyme haloperoxidases and efficiently brominate various phenol derivatives in the presence of KBr, H2O2, and HClO4 in the aqueous medium. Between these two complexes, 2 exhibits excellent catalytic activity with high turnover frequency (35.5-43.3 s-1) due to the strong electron-withdrawing nature of the cyano groups attached at β-positions and its moderate nonplanar structure as compared to 1 (TOF = 22.1-27.4 s-1). Notably, this is the highest turnover frequency value observed for any porphyrin system. The selective epoxidation of various terminal alkenes using complex 2 has also been carried out, and the results are good, specifying the importance of electron-withdrawing cyano groups. Catalysts 1 and 2 are recyclable, and the catalytic activity proceeds through the corresponding [VVO(OH)TPP(Br)4] and [VVO(OH)TPP(CN)4] intermediates, respectively.

Engineering Cytochrome P450BM3 Enzymes for Direct Nitration of Unsaturated Hydrocarbons.

Applications of the peroxidase activity of cytochrome P450 enzymes in synthetic chemistry remain largely unexplored. We present herein a protein engineering strategy to increase cytochrome P450BM3 peroxidase activity for the direct nitration of aromatic compounds and terminal aryl-substituted olefins in the presence of a dual-functional small molecule (DFSM). Site-directed mutations of key active-site residues allowed the efficient regulation of steric effects to limit substrate access and, thus, a significant decrease in monooxygenation activity and increase in peroxidase activity. Nitration of several phenol and aniline compounds also yielded ortho- and para-nitration products with moderate-to-high total turnover numbers. Besides direct aromatic nitration by P450 variants using nitrite as a nitrating agent, we also demonstrated the use of the DFSM-facilitated P450 peroxidase system for the nitration of the vinyl group of styrene and its derivatives.

Selective dimerization of terminal alkenes to form alkyl–alkyl products

Selective dimerization of terminal alkenes to form alkyl–alkyl products

Nickel-catalysed hydrodimerization of unactivated terminal alkenes

Nickel-catalysed hydrodimerization of unactivated terminal alkenes

A Fujiwara-Moritani-Type Alkenylation Using a Traceless Directing Group Strategy: A Rare Example of C-C Bond Formation towards the C2-Carbon of Terminal Alkenes.

Herein we report, a rhodium-catalyzed Fujiwara-Moritani-type reaction of unactivated terminal alkenes and benzoic acid derivatives bearing electron donating residues under mild conditions. The acid functionality acts as a traceless directing group delivering products alkenylated in meta-position to the electron donating substituent in contrast to the usually obtained ortho- and para-substitution in Friedel-Crafts-type reactions. Remarkably, the new C-C bond is formed to the C2 of the terminal olefin, in contrast to similar reported transformations. Initially formed mixtures of exo- and endo-double bond isomers can be efficiently isomerized to the more stable endo-products.

Allylsulfones through Palladium‐Catalyzed Allylic C−H Sulfonylation of Terminal Alkenes

AbstractTwo previously unknown protocols for Pd‐catalyzed allylic C−H sulfonylation of terminal alkenes have been developed. While the former consists of a direct Pd(II)‐catalyzed oxidative C−H allylic sulfonylation in the presence of sulfinate anions, the latter involves a sequential one‐pot Pd(II)‐catalyzed C−H allylic acetoxylation followed by a Pd(0)‐catalyzed sulfonylation. The scope of both protocols was studied on 25 examples.

Total Syntheses of Nominal and Actual Prorocentin.

The dinoflagellate-derived polyether prorocentin is a co-metabolite of the archetypical serine/threonine phosphatase inhibitor okadaic acid. Whereas a structural relationship cannot be missed and a biosynthetic link was proposed, it is currently unknown whether there is any parallel in the bioactivity profile of these natural products. However, it was insinuated in the past that the structure assigned to prorocentin might need to be revised. Indeed, re-examination of the published spectra cast doubts as to the constitution of the fused/spirotricyclic BCD-ring system in the core. To clarify this issue, a flexible synthesis blueprint was devised that allowed us to obtain the originally proposed structure as well as the most plausible amended structure. The key to success was late-stage gold-catalyzed spirocyclization reactions that furnished the isomeric central segments with excellent selectivity. The lexicon of catalytic transformations used to make the required cyclization precursors comprised a titanium-mediated ester methylenation/metathesis cascade, a rare example of a gold-catalyzed allylic substitution, and chain extensions via organocatalytic asymmetric aldehyde propargylation. A wing sector to be attached to the isomeric cores was obtained by Krische allylation, followed by a superbly selective cobalt-catalyzed oxidative cyclization of the resulting di-unsaturated alcohol with the formation of a 2,5-trans-disubstituted tetrahydrofuran; the remaining terminal alkene was elaborated into an appropriate handle for fragment coupling by platinum-catalyzed asymmetric diboration/oxidation. The assembly of the different building blocks to the envisaged isomeric target compounds proved that the structure of prorocentin needs to be revised as disclosed herein.