Allylic Isomerization Research Articles

Regioselective Ring‐Opening of Oxetanes Catalyzed by Lewis Superacid Al(C6F5)3

AbstractThis study details an aluminum‐catalyzed regioselective isomerization of 2,2‐disubstituted oxetanes to yield homoallylic alcohols. The reaction takes place in toluene at 40 °C, employing 1 mol % of Al(C6F5)3 as catalyst. This catalytic system shows a wide substrate scope (12 examples). The optimized conditions are especially useful for electron‐rich aryl oxetanes, completely suppressing the formation of allyl isomers and reducing the amount of the dimer by‐product. The synthetic applicability of the reported methodology is demonstrated by the enantioselective formal synthesis of curcuquinone and the σ1 receptor agonist RC‐33.

Isomerization-Free Matteson Homologations of Substituted Allylboronic Esters.

Substituted allyl derivatives with an internal double bond can be homologated under standard conditions via a 1,2-shift, whereas allylboronic esters with terminal double bonds can also be homologated via a SN' reaction. This allyl isomerization is catalyzed by ZnCl2 and can be suppressed by omitting ZnCl2 during the formation of α-chloroboronic ester. However, in the second step with Grignard reagents, ZnCl2 was added to suppress side reactions of the product formed.

Mechanism of the initial oxidation of monounsaturated fatty acids

The development of detection technology prompts the need to elaborate on the theory behind the oxidation of unsaturated fatty acids. This study integrates the detection of monounsaturated fatty acid oxidation at 60 °C with computational simulations to provide an advanced theoretical basis for the formation of hydroperoxides and allyl. The results indicate that oxidation reaction led to increases of 3.4 mg/g for 8-hydroperoxy-trans-9-octadecenoate (trans8) and 2.7 mg/g for 9-hydroperoxy-trans-10-octadecenoate (trans9) and 10-hydroperoxy-trans-8-octadecenoate (trans10) despite low temperatures. The energy of peroxyl radical production was 0.36 kcal/mol and that of allylic isomerization was 78.52 kcal/mol, indicating the existence of two pathways for hydroperoxides formation: β-fragmentation and the allylic isomerization. Structural equation modeling (SEM) verified the multistep competitive side reactions that occurred during oxidation. This finding provides a new basis for future analysis of lipid oxidation.

Potassium Base-Promoted Diastereoselective Synthesis of 1,3-Diols from Allylic Alcohols and Aldehydes through a Tandem Allylic-Isomerization/Aldol-Tishchenko Reaction.

This study reports the first base-promoted aldol-Tishchenko reactions of allylic alcohols with aldehydes initiated by allylic isomerization. The reaction enables the diastereoselective synthesis of a variety of 1,3-diols with three contiguous stereogenic centers. Unlike commonly reported systems, our method allows the use of readily available allylic alcohols as nucleophiles instead of enolizable aldehydes and ketones.

Potassium Base‐Catalyzed Michael Additions of Allylic Alcohols to α,β‐Unsaturated Amides: Scope and Mechanistic Insights

AbstractWe report herein the first KHMDS‐catalyzed Michael additions of allylic alcohols to α,β‐unsaturated amides through allylic isomerization. The reaction proceeds smoothly in the presence of only 5 mol% of KHMDS to afford a variety of 1,5‐ketoamides in high yields. Mechanistic investigations, including experimental and computational studies, reveal that the KHMDS‐catalyzed in‐situ generation of the enolate from the allylic alcohol through a tunneling‐assisted 1,2‐hydride shift is the key to the success of this transformation.magnified image

Concise Stereoselective Synthesis of β-Hydroxy-γ-lactones: (4R,5R)-4-Hydroxy-γ-decalactone from the Japanese Orange Fly and Enantiomers of Arachnid Harvestmen Isolates.

The naturally occurring (4R,5R)-4-hydroxy-γ-decalactone from the Japanese orange fly and the antipode of (4S,5R)-4-hydroxy-γ-dodecalactone from the harvestmen arachnid and their stereoisomers are synthesized from the chiral pool material d-glucono-δ-lactone in a few steps. The one-pot conversion of the latter to γ-vinyl-β-hydroxy-γ-lactone, cross-metathesis with requisite olefin, and hydrogenation enabled the synthesis of syn-lactones in just a two-pot operation. An additional efficient Pd-catalyzed allylic isomerization of γ-vinyl-β-hydroxy-γ-lactone led to the anti-lactones in high yields.

Pd(II)-Catalyzed alkyne annulation through allylic isomerization: synthesis of spiro-cyclopentadiene pyrazolones.

The Pd(ii)-catalyzed activation of Csp2-H bond and double alkyne annulation which proceeds via allylic isomerization is reported for the first time. This reaction of antipyrines with alkynes provides an efficient synthetic route for the biologically important spiro-cyclopentadiene pyrazolones. In the presence of Lawesson's reagent, this Pd(ii)-catalyzed annulation reaction affords another spiro-cyclopentadiene pyrazolone which displays very good fluorescence properties.

Selective 1,2‐Aminoisothiocyanation of 1,3‐Dienes Under Visible‐Light Photoredox Catalysis

AbstractSelective three‐component 1,2‐diamination of 1,3‐dienes with concurrent introduction of two orthogonally protected amino groups remains unknown despite its significant synthetic potential. We report herein that reaction of conjugated dienes with N‐aminopyridinium salts and TMSNCS affords 1,2‐aminoisothiocyanation products in a highly chemo‐ and regio‐selective manner under mild photoredox catalytic conditions. Mechanistic studies indicate that the facile isomerization of allyl thiocyanates to allyl isothiocyanates under photocatalytic conditions is responsible for the selective formation of the observed products. The mild isomerization protocol is expected to find applications in the synthesis of allyl isothiocyanates in a broad sense.

Selective 1,2-Aminoisothiocyanation of 1,3-Dienes Under Visible-Light Photoredox Catalysis.

Selective three-component 1,2-diamination of 1,3-dienes with concurrent introduction of two orthogonally protected amino groups remains unknown despite its significant synthetic potential. We report herein that reaction of conjugated dienes with N-aminopyridinium salts and TMSNCS affords 1,2-aminoisothiocyanation products in a highly chemo- and regio-selective manner under mild photoredox catalytic conditions. Mechanistic studies indicate that the facile isomerization of allyl thiocyanates to allyl isothiocyanates under photocatalytic conditions is responsible for the selective formation of the observed products. The mild isomerization protocol is expected to find applications in the synthesis of allyl isothiocyanates in a broad sense.

Nickel Tetracarbonyl as Starting Material for the Synthesis of NHC‐stabilized Nickel(II) Allyl Complexes

A novel, useful in situ synthesis for NHC nickel allyl halide complexes [Ni(NHC)(η3‐allyl)(X)] starting from [Ni(CO)4], NHC and allyl halides is presented. The reaction of [Ni(CO)4] with (i) one equivalent of the corresponding NHC and (ii) with an excess of the corresponding allyl chloride at room temperature leads with elimination of carbon monoxide to complexes of the type [Ni(NHC)(η3‐allyl)(X)]. This approach was used to synthesize the complexes [Ni(tBu2Im)(η3‐H2C‐C(Me)‐CH2)(Cl)] (2), [Ni(iPr2ImMe)(η3‐H2C‐C(Me)‐CH2)(Cl)] (3), [Ni(iPr2Im)(η3‐H2C‐C(Me)‐CH2)(Cl)] (4), [Ni(iPr2Im)(η3‐H2C‐C(H)‐C(Me)2)(Br)] (5), [Ni(Me2ImMe)(η3‐H2C‐C(Me)‐CH2)(Cl)] (6), and [Ni(EtiPrImMe)(η3‐H2C‐C(Me)‐CH2)(Cl)] (7). The complexes 1 to 7 were characterized using NMR and IR spectroscopy and elemental analysis, and the molecular structures are provided for 2 and 7. The allyl nickel complexes 1–7 are stereochemically non‐rigid in solution due to (i) NHC rotation about the nickel‐carbon bond, (ii) allyl rotation about the Ni–η3‐allyl axis and (iii) π–σ–π allyl isomerization processes. The allyl halide complexes can be methylated as was demonstrated by the methylation of a number of the complexes [Ni(NHC)(η3‐allyl)(X)] with methylmagnesium chloride or methyllithium, which led to isolation of the complexes [Ni(Me2Im)(η3‐H2C‐C(Me)‐CH2)(Me)] (8), [Ni(tBu2Im)(η3‐H2C‐C(Me)‐CH2)(Me)] (9), [Ni(iPr2ImMe)(η3‐H2C‐C(Me)‐CH2)(Me)] (10), [Ni(iPr2Im)(η3‐H2C‐C(Me)‐CH2)(Me)] (11), [Ni(iPr2Im)(η3‐H2C‐C(H)‐C(Me)2)(Me)] (12), and [Ni(EtiPrImMe)(η3‐H2C‐C(Me)‐CH2)(Me)] (13). These complexes were fully characterized including X‐ray molecular structures for 10 and 11.

Structure and Chemical Reaction Mechanism of LigU, an Enzyme That Catalyzes an Allylic Isomerization in the Bacterial Degradation of Lignin.

LigU from Novosphingobium sp. strain KA1 catalyzes the isomerization of (4E)-oxalomesaconate (OMA) to (3Z)-2-keto-4-carboxy-3-hexenedioate (KCH) as part of the protocatechuate (PCA) 4,5-cleavage pathway during the degradation of lignin. The three-dimensional structure of the apo form of the wild-type enzyme was determined by X-ray crystallography, and the structure of the K66M mutant enzyme was determined in the presence of the substrate OMA. LigU is a homodimer requiring no cofactors or metal ions with a diaminopimelate epimerase structural fold, consisting of two domains with similar topologies. Each domain has a central α-helix surrounded by a β-barrel composed of antiparallel β-strands. The active site is at the cleft of the two domains. 1H nuclear magnetic resonance spectroscopy demonstrated that the enzyme catalyzes the exchange of the pro-S hydrogen at C5 of KCH with D2O during the isomerization reaction. Solvent-deuterium exchange experiments demonstrated that mutation of Lys-66 eliminated the isotope exchange at C5 and that mutation of C100 abolished exchange at C3. The positioning of these two residues in the active site of LigU is consistent with a reaction mechanism that is initiated by the abstraction of the pro-S hydrogen at C3 of OMA by the thiolate anion of Cys-100 and the donation of a proton at C5 of the proposed enolate anion intermediate by the side chain of Lys-66 to form the product KCH. The 1,3-proton transfer is suprafacial.

Thermal cyclopropyl—allyl rearrangement of gem-chlorofluorocyclopropanes under gas-phase pyrolysis conditions. Formation of chlorofluoroalkenes and 2-fluorobuta-1,3-dienes

The gas-phase pyrolysis of isomeric 2-chloro-2-fluoro-1-phenylcyclopropanes in a flow reactor at 250–430 °С gives 1-phenyl- and 3-phenyl-3-chloro-2-fluoropropenes. Under similar conditions, methyl-substituted gem-chlorofluorocyclopropanes undergo cyclopropyl—allyl isomerization accompanied by dehydrochlorination to form chlorofluoroalkenes and 2-fluoro-buta-1,3-dienes.

Aggregation of catalytically active Ru nanoparticles to inactive bulk, monitored in situ during an allylic isomerization reaction. Influence of solvent, surfactant and stirring.

The exploration of catalytic isomerization reactions of an allylic alcohol to ketone, in the presence of μ-oxo-triruthenium acetate as a precatalyst in alcohol solvents, has established that the catalyst is heterogeneous in nature and proceeds by means of the in situ formed Ru0 nanoparticles (Ru0NPs). This reaction is used as an indicator for evaluating the kinetics and mechanism for metallic NP formation and self-assembly. In ethanol, complete conversion of the reactant is achieved under all experimental conditions tested. Conversely, in iso-propanol or n-pentanol the catalytic particles swiftly lose activity and the reaction arrests after partial conversion. We conclude that, in ethanol the process of NP self-assembly results in the formation of active and stable NPs of a specific size, named C-particles. Consequently, we propose an additional step for the established mechanism of NP self-assembly, namely the aggregation of C-NPs to inactive bulk-metal, labeled as D (C + C → D). D-particles differ from other NPs present in the catalytic cycle in size and in the catalytic activity. The effect of surfactant and mixing is also explored and the acquired observations strongly support the proposed mechanism of catalyst formation and decay. Addition of surfactants and/or mixing slowed down the reaction rate but dramatically improved the lifetime of the catalyst and the observed conversions. We attribute this phenomenon to the inhibition of the aggregation step of the active C-NPs to inactive D bulk-metal. The aggregation step of C-NPs to inactive D-bulk is assumed for the first time. This assumption prompts all the experimental data to be consistent. Introduction of the new kinetic step enables the use of the proposed mechanism with the reactions, where the catalyst loses its activity in the course of the reaction, and it converts the mechanism of the metal NP self-assembly into the more universal form.

NBu4NOTf-promoted radical self-hydrogen transferring isomerization under transition metal-free conditions

We report the first allylic isomerization of alcohols catalyzed by nBu4NOTf generated in situ from tetrabutylammonium triflate and potassium tert-butoxide.

Electrophilic and nucleophilic addition reactions of Ir(1-2,5-η-CH2CHCHCHSO2)(PMe3)3 with HBF4, acetonitrile, CO, pyridine and methanol: Haptotropic behavior of the butadienesulfonyl ligand

Reaction of IrCl(PMe3)3 with one equivalent of K(SO2CHCHCHCH2) led to the formation of Ir(1-2,5-η-CH2CHCHCHSO2)(PMe3)3 (1). The reaction of 1 with HBF4⋅Et2O takes place rapidly at low temperature to give the metallacycle [Ir(2,5-η-MeCHCHCHSO2)(PMe3)3]BF4 (2). Complex 2 reacts with CH3CN, CD3CN and CO to give the corresponding adducts [Ir(2,5-η-MeCHCHCHSO2)(PMe3)3(L)]BF4 (L = CH3CN, 3; CD3CN, 3D; CO, 4). Interestingly, compound 2 in the presence of pyridine or deuterated pyridine isomerizes to the terminal allyl compound [Ir(1-3,5-η-CH2CHCHCH2SO2)(PMe3)3]BF4 (5), while in the presence of oxygenated solvents, such as methanol, acetone and water, or their corresponding deuterated solvents, affords a mixture of cationic internal allyl isomers [Ir(2-4,6-η-MeCHCHCHSO2)(PMe3)3]BF4 (6a) and [Ir(2-4,5-η-MeCHCHCHSO2)(PMe3)3]BF4 (6b), being 6a always the major isomer. The iridium center is coordinated to an oxygen atom of the sulfone moiety in 6a, while for 6b coordination through the sulfur atom is proposed. Single-crystal X-ray diffraction studies of 5 and 6a confirm the unprecedented formation of novel sulfone-pentenyl ligands bonded to the iridium center through an η3 interaction and also by S and O coordination affording six-membered pseudo-ring structures. The mechanism of the formation of 5 and the mixture of isomers 6a and 6b is discussed. A comparative study with the thiapentadienyl analogue Ir(1-2,5-η-CH2CHCHCHS)(PMe3)3 (1S) is also considered.

Molecular cloning and functional identification of a cDNA encoding 4-hydroxy-3-methylbut-2-enyl diphosphate reductase from Tripterygium wilfordii

The 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR) is the last step key enzyme of the methylerythritol phosphate (MEP) pathway, synthesizing isopentenyl diphosphate and its allyl isomer dimethylallyl diphosphate, which is important for regulation of isoprenoid biosynthesis. Here the full-length cDNA of HDR, designated TwHDR (GenBank Accession No. KJ933412.1), was isolated from Tripterygium wilfordii for the first time. TwHDR has an open reading frame (ORF) of 1386bp encoding 461 amino acids. TwHDR exhibits high homology with HDRs of other plants, with an N-terminal conserved domain and three conserved cysteine residues. TwHDR cDNA was cloned into an expression vector and transformed into an Escherichia coli hdr mutant. Since loss-of-function E.coli hdr mutant is lethal, the result showed that transformation of TwHDR cDNA rescued the E.coli hdr mutant. This complementation assay suggests that the TwHDR cDNA encodes a functional HDR enzyme. The expression of TwHDR was induced by methyl-jasmonate (MJ) in T. wilfordii suspension cells. The expression of TwHDR reached the highest level after 1h of MJ treatment. These results indicate that we have identified a functional TwHDR enzyme, which may play a pivotal role in the biosynthesis of diterpenoid triptolide in T. wilfordii.

Mg(OMe)2 promoted allylic isomerization of γ-hydroxy-α,β-alkenoic esters to synthesize γ-ketone esters

This work concerns the Mg(OMe)2 promoted allylic isomerization of γ-hydroxy-α,β-alkenoic esters with TMEDA as an additive. The isomerization proceeded under mild conditions and afforded γ-keto esters in high yield (up to 96%) within 2 h. Both (Z)- and (E)-γ-hydroxy-α,β-alkenoic esters were tolerated under the reaction conditions. This transformation involves the in situ formation of a dienolate intermediate from the easily accessible γ-hydroxy-α,β-alkenoic ester. The in situ generated dienolate can react with benzaldehyde and undergo a practical, useful tandem allylic isomerization-Aldol reaction to afford more functionalized compounds.

Indole synthesis by palladium-catalyzed tandem allylic isomerization - furan Diels-Alder reaction.

A Pd(0)-catalyzed elimination of an allylic acetate generates a π-allyl complex that is postulated to initiate a novel intramolecular Diels-Alder cycloaddition to a tethered furan (IMDAF). Under the reaction conditions, this convergent, microwave-accelerated cascade process provides substituted indoles in moderate to good yields after Pd-hydride elimination, aromatization by dehydration, and in situ N-Boc cleavage.

Nickel‐Catalyzed Allylic C(sp2)–H Activation: Stereoselective Allyl Isomerization and Regiospecific Allyl Arylation of Allylarenes

Stereoselective allyl isomerization and regiospecific allyl arylation reactions of allylarenes with a catalytic system comprising nickel(II) with an aryl Grignard reagent were studied. Both reactions are triggered by allylic internal C(sp2)–H activation by in‐situ‐formed Ni0, which is inserted into the C–H bond at the 2‐position of the allyl moiety without a directing group. The isomerization of allylarene to 1‐propenylarene favors the E isomer and proceeds with quantitative conversion. The arylation takes place through oxidative cross‐coupling of allylarenes with excess Grignard reagent. It occurs regiospecifically at the position of C(sp2)–H activation and represents a new method for the synthesis of 1,1‐disubstituted olefins. The results of deuterium labeling experiments reveal an alkenyl/alkyl mechanism involving allylic internal C(sp2)–H activation and multiple intermolecular 1,2‐, 1,3‐, and 2,3‐hydride shifts. These methods represent new approaches to the functionalization of olefins, and the mechanistic investigations could be helpful for the discovery and design of new strategies for olefin functionalization.

Catalytic redox isomerization of allylic alcohols with rhodium and iridium complexes with ferrocene phosphine-thioether ligands

Complexes [M(P,SR)(diene)X] where (P,SR)=CpFe[1,2-C5H3(PPh2)(CH2SR)] (M=Ir, R=tBu or Bn diene=cod, X=Cl; M=Rh, diene=cod or nbd; X=BF4 or Cl) were used as precatalysts for the redox isomerization of various allylic alcohols (7a–e) to the corresponding saturated ketones (8a–e) and or hydrogenation to the saturated alcohol (9a–e). In optimization studies using 1-phenyl-2-propen-1-ol (7a) in THF and in iPrOH/MeONa, the only observed product was the saturated alcohol 1-phenyl-1-propanol (9a) when working under a 30bar H2 pressure, but activation for only 1min under H2 pressure and then continuation under 1bar of H2 or Ar led to increasing amounts of the allylic isomerization product propiophenone (8a). Continued reaction under H2 converted (8a) into (9a). The Rh precatalysts were more active than the Ir analogues. For the rhodium precatalysts (3) and (4), the redox isomerization reaction could be carried out after precatalyst activation in iPrOH/MeONa under Ar at 82°C (without H2) with complete conversion in 1h (1% catalyst loading). However, longer reaction times resulted in slow transfer hydrogenation of (8a) leading to (9a) with low enantiomeric excess. Extension of the H2-free activation of the Rh precatalysts in iPrOH to other allylic alcohol substrates (7b–d) yielded the corresponding ketones with good to excellent yields and excellent chemoselectivities under appropriate conditions.