Meyer-Schuster Rearrangement Research Articles

Keggin structure heteropolyacid-catalyzed phosphinylation of secondary propargyl alcohols with phosphine oxides to γ-ketophosphine oxides.

Phosphotungstic acid with a Keggin structure as an efficient, simple and green catalyst for the phosphinylation of secondary propargyl alcohols with phosphine oxides to afford γ-ketophosphine oxides with up to 88% isolated yield was developed using dimethyl carbonate as a green solvent. Diaryl- or alkylaryl-substituted propargyl alcohols, and diaryl or arylalkylphosphine oxides could tolerate the system, which reduced the catalyst dosage, and avoided the use of multi-components and toxic solvents. More interestingly, phosphotungstic acid exhibited the best activity when 0.58 moles of water were added per mole of HPWA, elevating the yield from 55% to 85%. An 18O labelled product was afforded using trace H218O instead of H2O, indicating the participation of water in the reaction. Besides, our work underscores the importance and effect of a small amount of water, acting to promote the transformation of secondary propargyl alcohols into enones, which should be the real intermediates of the reaction. A mechanism involving a carbocation, Meyer-Schuster rearrangement and Michael addition of enones was proposed.

Crystal Structure of the Monocarborane Magnesium(II) Acetylide and Its Use in the Synthesis of α,β-Unsaturated Ketones.

We report the first crystal structure of heteroleptic Grignard reagent 2 based on the carborane endo/exo dianion [CB11H11-12-C≡C]2-. Full characterization reveals a rare coordination pattern and affirms the bimetallic nature. Navigating the reactivity landscape, we unlock the potential of 2 in nucleophilic addition with ketones to afford propargylic alcohols 3, renowned for their synthetic versatility and potential biological activities, and unveil the Meyer-Schuster rearrangement, yielding α,β-unsaturated carbonyl compounds 4. This narrative of synthesis, characterization, and reactivity opens new horizons for carborane chemistry, offering avenues for innovation and facile functionalization of carborane scaffolds.

Regiocontrolled Ruthenium-Catalyzed Isomerization of Propargyl Alcohols

AbstractA diaminocyclopentadienone ruthenium complex allows control of regioselectivity in the ruthenium-catalyzed isomerization of propargyl alcohols through the choice of additive. Thereby, both products of the Meyer–Schuster rearrangement and redox isomerization products are selectively accessible. In the presence of hydroxylamine-O-sulfonic acid, unsaturated nitriles are formed instead. The ruthenium catalyst is readily available and stable to moisture, air, and acidic conditions.

Multifunctional Biomass-Based Ionic Liquids/CuCl-Catalyzed CO2-Promoted Hydration of Propargylic Alcohols: A Green Synthesis of α-Hydroxy Ketones.

α-Hydroxy ketones are a class of vital organic skeletons that generally exist in a variety of natural products and high-value chemicals. However, the traditional synthetic route for their production involves toxic Hg salts and corrosive H2SO4 as catalysts, resulting in harsh conditions and the undesired side reaction of Meyer-Schuster rearrangement. In this study, CO2-promoted hydration of propargylic alcohols was achieved for the synthesis of various α-hydroxy ketones. Notably, this process was catalyzed using an environmentally friendly and cost-effective biomass-based ionic liquids/CuCl system, which effectively eliminated the side reaction. The ionic liquids utilized in this system are derived from natural biomass materials, which exhibited recyclability and catalytic activity under 1 bar of CO2 pressure without volatile organic solvents or additives. Evaluation of the green metrics revealed the superiority of this CuCl/ionic liquid system in terms of environmental sustainability. Further mechanistic investigation attributed the excellent performance to the ionic liquid component, which exhibited multifunctionality in activating substrates, CO2 and the Cu component.

Synthesis of 2-acyl benzofurans and indoles based on nucleophile-intercepted Meyer–Schuster rearrangement of o-hydroxyphenyl and o-aminophenyl propargylic alcohols

A new type of nucleophile-intercepted Meyer–Schuster rearrangement mediated by pyridine N-oxide under metal-free conditions using a catalytic amount of acid is disclosed. It enables synthesis of 2-acyl benzofurans and indoles in 56–>99% yields.

Development of the Meyer–Schuster Rearrangement on Propargylic Alcohols with Fluorinated Chains

AbstractThe Meyer–Schuster Rearrangement (MSR) is a challenging process for propargylic alcohols bearing fluorine atom(s) on their chains. Most classical reagents/catalysts failed to perform the MSR but, after extensive screening, we demonstrated that phosphomolybdic acid was the first efficient catalyst for the MSR with such derivatives. The scope and limitations have been studied, affording fluorine‐containing enones as useful intermediates for the synthesis of targets with fluorine(s) on their side chains. It was exemplified by the preparation of a 2‐piperidino‐pyrimidine and a pyrazole.

SOCl2-Catalyzed Meyer-Schuster Rearrangement of 3°-Propargylic Alcohols: Synthesis of Densely Arene-Substituted Pyrazolines Bearing Quaternary Centers from α,β-Unsaturated Carbonyl Compounds and Arylhydrazines.

Meyer-Schuster rearrangement of 3°-propargyl alcohol to the corresponding α,β-unsaturated carbonyl compounds under SOCl2 catalysis has been reported. Terminal and internal propargyl alcohols efficiently participated in the reaction. Furthermore, we have demonstrated the synthetic utility of conjugated carbonyl compounds to access densely arene-substituted pyrazolines bearing quaternary centers by reacting with arylhydrazine hydrochloride. Isotopic labeling studies were carried out to gain insights into the reaction mechanism.

Nonclassical Arylative Meyer–Schuster Rearrangement through Ni-Catalyzed Inner-Sphere Acyloxy Migration

Nonclassical Arylative Meyer–Schuster Rearrangement through Ni-Catalyzed Inner-Sphere Acyloxy Migration

Cu(II)-Catalyzed Decarboxylative (4 + 2) Annulation of Coumarin-3-Carboxylic Acids with In Situ Generated α,β-Unsaturated Carbonyl Compounds from tert-Propargylic Alcohols

Cu(II)-catalyzed decarboxylative oxidative (4 + 2) annulation of coumarin-3-carboxylic acids with tert-propargylic alcohols, via the in situ generated α,β-unsaturated carbonyl compounds by the Meyer-Schuster rearrangement, has been developed. This protocol involving indirect C-H functionalization offers access to diverse naphthochromenone architectures with good to excellent yields.

Improved synthesis of deoxyalpinoid B and quantification of antileishmanial activity of deoxyalpinoid B and sulforaphane

The total synthesis and antileishmanial activity of deoxyalpinoid B is reported via a cationic gold-catalyzed Meyer-Schuster rearrangement. The activity of deoxyalpinoid B and a known inducer of oxidative stress, sulforaphane, against Leishmania donovani and Leishmania infantatum are both reported for the first time. Both compounds exhibit potent antileishmanial activity against both species. We hypothesize that the activation of intracellular oxidative stress is a key molecular response for the inhibition of Leishmania.

Stereoselective Synthesis of Acyclic Skeleton of Boscartin A

AbstractStereoselective synthesis of key acyclic skeleton of structurally challenging and biologically active boscartin A possessing six stereogenic centers, among which three are tertiary, has been achieved for the first time. The synthetic study comprises the Sharpless asymmetric epoxidation (SAE) followed by stereoselective epoxide opening for installation of C-11 and C-12 centers, Meyer–Schuster rearrangement followed by intramolecular oxa-Michael addition for construction of C-1 center, SAE followed by CBS reduction and subsequent cycloetherification for stereoselective generation of C-3, C-4, and C-7 centers, Gilman reaction for introduction of C-9 olefin and Grignard reaction for installation of C-8 olefin.

Efficient total synthesis of three alpinoids via the Au(I)-catalyzed Meyer-Schuster rearrangement

The total syntheses of three structurally related natural products, deoxyalpinoid B, deoxyalpinoid A, and alpinoid F, are reported, and each features a Au(I)-catalyzed Meyer-Schuster rearrangement as the key step. The synthesis of alpinoid F is reported for the first time. The syntheses of these natural products, all of which exhibit potent anticancer activity, are readily amenable to the preparation of structural analogs.

One-Pot Synthesis of Push–Pull Butadienes from 1,3-Diethyl-2-thiobarbituric Acid and Propargylic Alcohols

A new synthetic procedure for obtaining two previously reported donor-acceptor butadiene dyes, namely 5-(3,3-bis(4-methoxyphenyl)allylidene)-1,3-diethyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione and 5-(3,3-bis(4-(dimethylamino)phenyl)allylidene)-1,3-diethyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione, based on the InCl3-catalyzed coupling 1,3-diethyl-2-thiobarbituric acid with 1,1-bis(4-methoxyphenyl)prop-2-yn-1-ol and 1,1-bis(4-(dimethylamino)phenyl)prop-2-yn-1-ol, respectively, is presented. The reactions, which cleanly proceed in water under MW irradiation, involve the initial generation of the corresponding enals by Meyer-Schuster rearrangement of the alkynols and their subsequent Knoevenagel condensation with the 2-thiobarbituric acid derivative. By following the same approach, the novel butadiene 5-(3,3-bi([1,1′-biphenyl]-4-yl)allylidene)-1,3-diethyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione, which was characterized by 1H and 13C{1H} NMR, IR, UV-Vis, elemental analysis and HRMS, was synthesized in 79% yield.

Activation of o-Propargyl Alcohol Benzaldehydes under Acetalization Conditions for Intramolecular Electrophile Intercepted Meyer-Schuster Rearrangement.

The reactivity of o-propargyl alcohol benzaldehydes has been increased tremendously toward Brønsted acid-catalyzed intramolecular electrophile intercepted Meyer-Schuster (M-S) rearrangement under acetalization conditions using trimethyl orthoformate (TMOF). The in situ formed acetal transfers the methoxy group intramolecularly to generate the M-S intermediate in even less reactive substrates, and the formed oxocarbenium ion makes the carbonyl more electrophilic for an effective intramolecular trapping of the M-S intermediate to furnish the indanone derivatives.

Tandem Macrolactone Synthesis: Total Synthesis of (−)‐Exiguolide by a Macrocyclization/Transannular Pyran Cyclization Strategy

AbstractTetrahydropyran‐containing macrolactones were synthesized by integrating Meyer–Schuster rearrangement, macrocyclic ring‐closing metathesis, and transannular oxa‐Michael addition under gold and ruthenium catalysis. Single‐step access to a variety of 14‐ to 20‐membered macrolactones containing a tetrahydropyran ring was possible from readily available linear precursors in good yields and with moderate to excellent diastereoselectivity. A 13‐step synthesis of (−)‐exiguolide, an anticancer marine macrolide, showcased the feasibility of our tandem reaction sequence for macrolactone synthesis and also demonstrated the power of transannular reactions for rapid assembly of the tetrahydropyran rings of the target natural product.

Tandem Macrolactone Synthesis: Total Synthesis of (-)-Exiguolide by a Macrocyclization/Transannular Pyran Cyclization Strategy.

Tetrahydropyran-containing macrolactones were synthesized by integrating Meyer-Schuster rearrangement, macrocyclic ring-closing metathesis, and transannular oxa-Michael addition under gold and ruthenium catalysis. Single-step access to a variety of 14- to 20-membered macrolactones containing a tetrahydropyran ring was possible from readily available linear precursors in good yields and with moderate to excellent diastereoselectivity. A 13-step synthesis of (-)-exiguolide, an anticancer marine macrolide, showcased the feasibility of our tandem reaction sequence for macrolactone synthesis and also demonstrated the power of transannular reactions for rapid assembly of the tetrahydropyran rings of the target natural product.

Bi(OTf)3-Catalyzed Alkyl-Intercepted Meyer-Schuster Rearrangement of Propargylic Alcohols for the Synthesis of 1,2,3,5-Tetrasubstituted Pentane-1,5-diones.

An alkyl intercepted Meyer-Schuster rearrangement reaction with α,β-unsaturated ketones as the electrophiles was first investigated, which provided a facile method to construct 2-methylene-pentane-1,5-diones. Then the in situ generated 2-methylene-pentane-1,5-diones underwent a Michael addition to give diverse 2-malononitrile methyl substituted pentane-1,5-diones in a one-pot fashion. This transformation was reliable on a gram scale. The high yield, convenient experimental operation, and 100% atom economy made it a valuable method for the construction of 1,2,3,5-tetrasubstituted pentane-1,5-dione derivatives.

Meyer-Schuster rearrangement of propargylic alcohols mediated by phosphorus-containing Brønsted acid catalysts.

Commercially available (aqueous) hypophosphorus acid is an efficient catalyst for the synthesis of α,β-unsaturated carbonyl compounds from their corresponding propargylic alcohols. Reactions were carried out in technical toluene in the presence of air and in several instances the desired products were isolated analytically pure after a simple work-up.

Electrophilic halogenations of propargyl alcohols: paths to α-haloenones, β-haloenones and mixed β,β-dihaloenones.

The Meyer–Schuster rearrangement of propargyl alcohols or alkynols leading to α,β-unsaturated carbonyl compounds is well known. Yet, electrophilic halogenations of the same alkynols and their alkoxy, ester and halo derivatives are inconspicuous. This review on the halogenation reactions of propargyl alcohols and derivatives intends to give a perspective from its humble direct halogenation beginning to the present involving metal catalysis. The halogenation products of propargyl alcohols include α-fluoroenones, α-chloroenones, α-bromoenones and α-iodoenones, as well as β-haloenones and symmetrical and mixed β,β-dihaloenones. They are, in essence, tri and tetrasubstituted alkenes carrying halo-functionalization at the α- or β-carbon. This is a potential stepping stone for further construction towards challenging substituted alkenones via Pd-catalysed coupling reactions.

Gold (I)-Promoted Intermolecular Cascade Annulation to Access 2-Hydroxybenzocarbazoles via a Meyer-Schuster Rearrangement.

An efficient cascade annulation protocol was established to access substituted 2-hydroxybenzocarbazoles from alkynylcyclohexadienones and substituted 2-aminophenols under gold catalysis. In this transformation a new C-C, two C-N bonds were formed sequentially and moderate to excellent yields of 2-hydroxybenzocarbazole derivatives were obtained selectively via Meyer-Schuster rearrangement in one-pot.