Deficient Olefins Research Articles

A Concise Synthesis of (2R,6R)-Hydroxynorketamine.

A concise synthesis of (2R,6R)-hydroxynorketamine was accomplished in eight steps, starting from commercially available materials. This synthesis features a cerium chloride-enhanced Stork-Danheiser reaction, an asymmetric reduction of ketone by the Corey-Bakshi-Shibata reaction, a signature Overman rearrangement, and a facial selective dihydroxylation of an electronically deficient olefin by RuCl3/NaIO4. The overall yield is 7.3% with 94.5% ee.

Thiophane‐Catalyzed Umpolung of N‐Bromoimides for Dibromination of Olefins

AbstractA thiophane‐catalyzed dibromination of olefins using NBS as the sole bromine source has been developed, providing a low‐cost and mild methodology for preparing vicinally dibrominated compounds from electron‐neutral or ‐deficient alkenes. The mechanistic investigation showed that 2,3‐dihydrothiophene generated in situ from the reaction of thiophane with NBS was the actual catalyst, which reversed the polarity of NBS to yield bromide ion.

Introduction of Chiral Centers to α- and/or β-Positions of Carbonyl Groups by Biocatalytic Asymmetric Reduction of α,β-Unsaturated Carbonyl Compounds

Biocatalytic asymmetric reductions of acyclic and cyclic α,β-unsaturated carbonyl compounds are favorable protocols for introduction of chiral centers to α- and/or β-positions of the carbonyl groups. Representative biocatalytic reductions of electron deficient olefins are compiled from a synthetic point of view according to compound types from the papers in 2012 to early 2022. Applications to syntheses of some enantiomericaly enriched perfumery ingredients are presented to show the feasibility of the biocatalytic reductions.

Iron-Catalyzed Photoinduced LMCT: a 1° C-H Abstraction Enables Skeletal Rearrangements and C(sp3)-H Alkylation.

Herein we disclose an iron-catalyzed method to access skeletal rearrangement reactions akin to the Dowd-Beckwith ring expansion from unactivated C(sp3)-H bonds. Photoinduced ligand-to-metal charge transfer at the iron center generates a chlorine radical, which abstracts electron-rich C(sp3)-H bonds. The resulting unstable alkyl radicals can undergo rearrangement in the presence of suitable functionality. Addition to an electron deficient olefin, recombination with a photoreduced iron complex, and subsequent protodemetallation allows for redox-neutral alkylation of the resulting radical. Simple adjustments to the reaction conditions enable the selective synthesis of the directly alkylated or the rearranged-alkylated products. As a radical clock, these rearrangements also enable the measurement of rate constants of addition into various electron deficient olefins in the Giese reaction.

Organocatalytic Enantioselective Intramolecular (Hetero)Michael Additions in Desymmetrization Processes

AbstractThe organocatalytic enantioselective desymmetrization reaction by means of an intramolecular (hetero)Michael addition is a useful strategy for the creation of complex carbo‐ and heterocycles with the generation of multiple stereocenters in a very simple manner. The intramolecular addition of carbon, oxygen and nitrogen nucleophiles to prochiral substrates bearing electronically deficient olefins takes place in the presence of organocatalysts, such as chiral primary and secondary amines, NHCs, ureas, thioureas, and BINOL phosphoric acid derivatives, reaching high levels of diastereo‐ and enantioselectivity. The main bottleneck of this methodology is the design and synthesis of the starting materials, which compromises its application. To date, the majority of examples are related to the use of 1,4‐cyclohexanedione derivatives.

Photoredox Generation of Sulfonyl Radicals and Coupling with Electron Deficient Olefins.

Various sulfone tetrazoles were activated via iridium photoredox catalysis in the presence of DMAP to give dialkyl sulfones. The presumed sulfone radical intermediates were trapped by a range of electron-deficient olefins in generally good to excellent yields.

Solvent‐ and Catalyst‐Free Aza‐Michael Addition of Imidazoles and Related Heterocycles

This work demonstrates the scope and limitations of the aza‐Michael addition of imidazoles and related heterocycles with electron deficient olefins under solvent‐ and catalyst‐free conditions. The reaction proceeds at 80 °C within hours towards completion as long as the azole derivative is sufficiently soluble in the Michael acceptor, which has been used in small excess. Workup only comprises evaporation of surplus Michael‐acceptor, and no additional solvents are necessary for purifying the products.

Pyrenediones as versatile photocatalysts for oxygenation reactions with in situ generation of hydrogen peroxide under visible light

Pyrenediones (PYDs) are efficient photocatalysts for three oxygenation reactions: epoxidation of electron deficient olefins, oxidative hydroxylation of organoborons and oxidation of sulfides via in situ generation of H2O2 from O2 under visible light irradiation.

The Synthesis of Hydrobenzoin-Based Monoaza Crown Ethers and Their Application as Recyclable Enantioselective Catalysts

New recyclable monoaza-15-crown ethers have been synthesized starting from (R,R)-(+)- and (S,S)-(−)-hydrobenzoin. These macrocycles proved to be efficient and reusable phase transfer catalysts in a few asymmetric reactions under mild conditions. The asymmetric epoxidation of trans-chalcone took place with up to 81% ee, while using other chalcone derivatives, the products were formed with 68–88% ee. The hydrobenzoin-based lariat ethers were also tested in the cyclopropanation of a few electron deficient olefins using diethyl bromomalonate to afford the product with good enantioselectivities (54–75% ee). The catalysts were recovered by salt formation, followed by extraction, and were reused without the loss of the activity and effect on the enantioselectivity.Graphic The synthesis of hydrobenzoin-based monaza crown ethers and their application as recyclable enantioselective catalysts.

Cobalt-Salen Catalyzed Electroreductive Alkylation of Activated Olefins

Cobalt-Salen mediated electroreductive and regioselective alkylation of electron deficient olefins is reported in one step in an undivided electrochemical cell, in the presence of an iron rod as sacrificial anode. Although the reactivity depends on the class of alkyl halides, the reported study offers a green and expeditious electrosynthetic route for Csp3-Csp3 bond formation in mild conditions. This study also confirms the possible formation of the heterobinuclear cobalt-Salen-iron complex previously reported as the effective catalyst.

Enantioselective conjugate addition of an α,α-dithioacetonitrile with nitroalkenes using chiral bis(imidazoline)-Pd complexes.

The enantioselective conjugate addition reaction of an α,α-dithioacetonitrile with nitroalkenes was catalysed by chiral bis(imidazoline)-palladium pincer-type complexes. The reaction was applicable to various nitroalkenes to afford products in good yield with high enantioselectivity. The obtained products can be converted to γ-lactam and biologically active rolipram.

Synthesis of 4‐Alkenyl Benzoxazoles via Pd‐catalyzed ortho C−H Functionalization of 2‐Amidophenols

AbstractA one‐pot direct transformation to remotely C−H alkene functionalized 2‐aryl benzoxazoles from the reaction of amidophenol and electronically deficient olefin was reported. Control experiments confirm that the Pd‐catalyzed regioselective C−H activation/alkenylation occurs at the first step by leading to ortho‐alkenylated amidophenol; which subsequently underwent tandem intramolecular annulation to afford C4‐alkenylated 2‐arylbenzoxazole derivatives.magnified image

Multi-functionalized ionic liquid with in situ-generated palladium nanoparticles for Suzuki, Heck coupling reaction: a comparison with deep eutectic solvents

A new catalytic system for Suzuki and Heck coupling has been developed from multi-functionalized task specific ionic liquid (TSIL) and in situ formed palladium nanoparticles (PdNps). The generated PdNPs were characterized by UV–Visible spectroscopy and transmission electron microscopy (TEM) analysis. These PdNPs have found size below 10 nm and exhibited a excellent catalytic activity in the cross-coupling of aryl halide without using external phosphine ligand. Along with electron deficient olefins, electron rich olefins were also undergo smooth reaction giving excellent yield. The results obtained in ionic liquid are compared with results obtained in deep eutectic solvents. Progress of reaction was found very smooth in ionic liquid rather than in deep eutectic solvents. The aqueous system containing ionic liquid along with PdNPs was recycled for seven times, without any significant loss.

Visible-Light-Induced Intramolecular C(sp2)-H Amination and Aziridination of Azidoformates via a Triplet Nitrene Pathway.

Catalytic intramolecular C-H amination and aziridination reactions of o-allylphenyl azidoformates have been achieved under visible-light irradiation, providing a mild, clean, and efficient method for the synthesis of useful benzoxazolones and [5.1.0] bicyclic aziridines. Mechanistic studies suggest that a triplet nitrene acts as the reactive intermediate. The chemoselectivity of the reaction, with alkyl olefin aziridination ≫ electron deficient olefin aziridination ≈ C(sp2)-H amination ≫ C(sp3)-H amination was observed, which may be instructive in the development of an understanding of visible-light-induced triplet nitrene transformation reactions.

Exploiting λ-Orthogonal Photoligation for Layered Surface Patterning.

We exploit λ-orthogonal photoligation of nitrile imine-mediated tetrazole-ene cycloaddition (NITEC) chemistry to generate complex, interconnected surface modifications via a simple layered surface patterning approach. By judicious choice of activating chromophores, we introduce a one pot reaction where nitrile imine formation can be triggered independently of other tetrazoles present. When irradiated with visible light, a tetrazole bearing a pyrene chromophore undergoes quantitative elimination of nitrogen to release nitrile imine (which subsequently undergoes trapping with a dipolarophile in a 1,3 dipolar cycloaddition) whereas a tetrazole bearing a phenyl moiety remains unreacted. Subsequent irradiation of the solution with UV light yields the N-phenyl containing nitrile imine quantitatively, while the pyrene pyrazoline adduct remains unchanged. This λ-orthogonal photoligation was subsequently exploited for the generation of layered patterned surfaces. Specifically, the visible light active tetrazole was grafted to a silicon wafer and subsequently photolithographically patterned with a dipolarophile modified with a UV-active tetrazole. Various electron deficient olefins were then patterned in a spatially resolved manner relying on different light activation. The desired functionality was successfully imaged on the silicon wafers using time-of-flight-secondary ion mass spectrometry (ToF-SIMS), demonstrating that a powerful mask-less lithographic platform technology has been established.

Synthesis of Phenylpropanoids via Matsuda-Heck Coupling of Arene Diazonium Salts.

The Pd-catalyzed Heck-type coupling (Matsuda-Heck reaction) of electron rich arene diazonium salts with electron deficient olefins has been exploited for the synthesis of phenylpropanoid natural products. Examples described herein are the naturally occurring benzofurans methyl wutaifuranate, wutaifuranol, wutaifuranal, their 7-methoxy derivatives, and the O-prenylated natural products boropinols A and C.

ChemInform Abstract: N‐Methylpyrrolidone Hydroperoxide/Cs2CO3 as an Excellent Reagent System for the Hydroxy‐Directed Diastereoselective Epoxidation of Electron‐Deficient Olefins.

AbstractThe title reagent system is efficiently used for the chemoselective epoxidation of various hydroxy group‐containing electron deficient olefins, and the reaction is shown to proceed diastereoselectively if an unprotected hydroxy group is present and non‐diastereoselectively in case of protected analogues.

B(C6F5)3-Catalyzed transfer 1,4-hydrostannylation of α,β-unsaturated carbonyls using iPr-tricarbastannatrane.

Tris(pentafluorophenyl)borane, B(C6F5)3, has been found to be an effective catalyst to access the hydridoborate anion, [N(CH2CH2CH2)3Sn][HB(C6F5)3], via hydride abstraction from the hypercoordinated tin reagent, iPr-tricarbastannatrane. This process has been applied to the B(C6F5)3-catalyzed transfer 1,4-hydrostannylation of electron-deficient olefins, namely benzylidene barbituric acids. Insights into the mechanism have been obtained via a series of 1H, 2H, 11B, 13C, and 119Sn NMR spectroscopy, mass spectrometry, and labeling experiments.

Cyclopropanation of Various Substrates via Simmons-Smith and Michael-Initiated Ring Closure (MIRC) Reactions

Cyclopropanation of various electron rich and electron deficient olefins via Simmons-Smith and Michael-initiated ring closure reactions was studied in our research. Cinnamyl alcohol 18 was succesfully cyclopropanated in a good to excellent yield using Simmons-Smith reactions. Methyl and benzyl crotonate 14 and 16 were labile in MIRC reaction condition indicated by the detection of starting material degradation in the NMR spectra of the crude reactions, and allowed a low to moderate product yield. The other starting materials, i.e., cinnamaldehyde 19 , methyl cinnamate 20 , mono- and di-protected cross-coupled product (4 R ,5 R , E )-methyl 5-( tert -butyldimethylsilyloxy)-4-hydroxyhepta-2,6-dienoate 25 and (4 R ,5 R , E )-methyl 5-( tert -butyldimethylsilyloxy)-4-(methoxymethoxy)hepta-2,6-dienoate 26 , were apparently incompatible to the reaction condition set in our study.

Umpolung synthesis of branched α-functionalized amines from imines via photocatalytic three-component reductive coupling reactions.

A three component reductive coupling reaction of a (hetero)aromatic amine, a (hetero)aromatic aldehyde and an electron deficient olefin catalysed by eosin Y under green LED light irradiation, for the direct generation of γ-amino acid derivatives, is described. This new umpolung synthesis of amines, which exploits the high nucleophilicity of a putative α-amino radical intermediate, generated via single electron reduction of the in situ generated imine from the Hantzsch ester terminal reductant, is efficient, operationally simple, broad in scope and offers a complementary strategy to existing synthetic approaches.