Meyer-Schuster Rearrangement Research Articles

Gold-Catalyzed Synthesis of 2-Substituted Azepanes: Strategic Use of Soft Gold(I) and Hard Gold(III) Catalysts

Strategic use of both soft gold(I) and hard gold(III) catalysts provides azepanes from propargylic alcohols in one pot. Thus, propargylic alcohols in the presence of soft gold(I) catalyst (Ph3PAuNTf2) undergo a Meyer–Schuster rearrangement to give α,β-unsaturated ketones, which in turn undergo a gold(III) (AuBr3)-catalyzed aza-Michael addition to afford azepanes bearing a carbonyl group.

ChemInform Abstract: Cross‐Coupling of Meyer—Schuster Intermediates under Dual Gold—Photoredox Catalysis.

Under dual gold/photoredox catalytic conditions, intermediates from the Meyer-Schuster rearrangement underwent an efficient cross-coupling with arene diazonium salts, leading to α-arylated enones. Diazonium salts assisted the dissociation of the propargyl hydroxyl group by forming alkoxydiazenes in the Meyer-Schuster rearrangement, and the coupling was proposed to proceed through an allenyl methyl ether.

ChemInform Abstract: Elucidation of Mechanisms and Selectivities of Metal‐Catalyzed Reactions Using Quantum Chemical Methodology

AbstractReview: 46 refs.

Synthesis of 3-substituted indolizidines from amino-ynones derivatives

Two types of indolizidine derivatives can be synthesized from amino-ynones. In the presence of methanesulfonic acid, Meyer–Schuster rearrangement furnished vinylogues of indolizidin-3-ones whereas treatment with zinc chloride gave stable 3-alkynyl-1,5,6,7,8,8a-hexahydroindolizine-zinc complexes that were reduced to 3-alkynylindolizidines.

ChemInform Abstract: Study on the Synthesis of the Cyclopenta[f]indole Core of Raputindole A.

The raputindoles from the rutaceous tree Raputia simulans share a cyclopenta[f]indole partial structure the synthesis of which is subject of this investigation. An efficient route to a series of 1,5-di(indol-6-yl)pentenones was developed via Mo/Au-catalyzed Meyer–Schuster rearrangement of tertiary propargylic alcohol precursors. However, none of the enones underwent the desired Nazarov cyclization to a cyclopenta[f]indole. More suitable were 6-hydroxyallylated indolines which gave good yields of cyclopenta[f]indolines after treatment with SnCl4, as soon as sterically demanding β-cyclocitral adducts were reacted. Most successful were Pt(II) and Au(I)-catalyzed cyclizations of N-TIPS-protected indolin-6-yl-substituted propargylacetates which provided the hydrogenated tricyclic cyclopenta[f]indole core system in high yield.

Site‐Selective Calcium‐Catalyzed/Organocatalyzed Condensation of Propargyl Alcohols Tethered to β‐Keto Esters

AbstractThe intramolecular condensation of β‐keto esters to give propargyl alcohols is described. The substrates have two electrophilic sites and two nucleophilic sites. The site selectivity can be fully controlled. In the presence of a calcium‐based catalyst and under anhydrous conditions, O‐addition products are isolated. On the other hand, traces of water or iPrOH as additive encourage calcium‐catalyzed Meyer–Schuster rearrangements. The resulting enones may be further transformed into endo‐Michael addition products. The regioselectivity of the attack of the enolate can be changed by using 1‐[3,5‐bis(trifluoromethyl)phenyl]‐3‐[2‐(dimethylamino)cyclohexyl]thiourea (TUC) as organocatalyst, which promotes the formation of aldol‐condensation products of high synthetic interest. DFT calculations rationalize the preference for the aldol condensation when TUC is used instead of the endo‐Michael addition.

Intercepting the Gold-Catalysed Meyer-Schuster Rearrangement by Controlled Protodemetallation: A Regioselective Hydration of Propargylic Alcohols.

The regioselective gold‐catalysed hydration of propargylic alcohols to β‐hydroxy ketones can be achieved by diverting the gold‐catalysed Meyer–Schuster rearrangement through the addition of a protic additive with a pK a of 7–9 such as p‐nitrophenol, boric acid or a boronic acid. This provides an interesting alternative to an aldol reaction when combined with the straightforward addition of an alkyne to an aldehyde or ketone. The gold‐catalysed reaction of an electron‐deficient, sterically hindered propargylic alcohol with a boronic acid led to the formation of an unusually stable cyclic boron enolate.

Domino Meyer–Schuster/Arylation Reaction of Alkynols or Alkynyl Hydroperoxides with Diazonium Salts Promoted by Visible Light under Dual Gold and Ruthenium Catalysis

AbstractA method for the arylative coupling of alkynols or alkynyl hydroperoxides using equimolar amounts of diazonium salts at room temperature has been achieved through application of a gold/photoredox dual catalytic system. The excess of external reagents (oxidant or base) and high temperatures required by previous arylative Meyer–Schuster rearrangement protocols are avoided by exploitation of a visible light‐mediated process.magnified image

Investigation of Meyer–Schuster Rearrangement Promoted by a Samarium(III) Triflate/N‐Fluorobenzenesulfonimide Lewis Acid System

AbstractThe acceleration effect from the addition of N‐fluorobenzenesulfonimide (NFSI) to a samarium(III) triflate catalyzed Meyer–Schuster rearrangement under microwave irradiation was studied. Reaction rate plots indicate that the Sm(OTf)3/NFSI system is especially suitable for unreactive substrates towards the Meyer–Schuster rearrangement. The mechanism was probed by a crossover experiment using 18O‐labeled substrates.

Elucidation of Mechanisms and Selectivities of Metal-Catalyzed Reactions using Quantum Chemical Methodology.

Quantum chemical techniques today are indispensable for the detailed mechanistic understanding of catalytic reactions. The development of modern density functional theory approaches combined with the enormous growth in computer power have made it possible to treat quite large systems at a reasonable level of accuracy. Accordingly, quantum chemistry has been applied extensively to a wide variety of catalytic systems. A huge number of problems have been solved successfully, and vast amounts of chemical insights have been gained. In this Account, we summarize some of our recent work in this field. A number of examples concerned with transition metal-catalyzed reactions are selected, with emphasis on reactions with various kinds of selectivities. The discussed cases are (1) copper-catalyzed C-H bond amidation of indoles, (2) iridium-catalyzed C(sp(3))-H borylation of chlorosilanes, (3) vanadium-catalyzed Meyer-Schuster rearrangement and its combination with aldol- and Mannich-type additions, (4) palladium-catalyzed propargylic substitution with phosphorus nucleophiles, (5) rhodium-catalyzed 1:2 coupling of aldehydes and allenes, and finally (6) copper-catalyzed coupling of nitrones and alkynes to produce β-lactams (Kinugasa reaction). First, the methodology adopted in these studies is presented briefly. The electronic structure method in the great majority of these kinds of mechanistic investigations has for the last two decades been based on density functional theory. In the cases discussed here, mainly the B3LYP functional has been employed in conjunction with Grimme's empirical dispersion correction, which has been shown to improve the calculated energies significantly. The effect of the surrounding solvent is described by implicit solvation techniques, and the thermochemical corrections are included using the rigid-rotor harmonic oscillator approximation. The reviewed examples are chosen to illustrate the usefulness and versatility of the adopted methodology in solving complex problems and proposing new detailed reaction mechanisms that rationalize the experimental findings. For each of the considered reactions, a consistent mechanism is presented, the experimentally observed selectivities are reproduced, and their sources are identified. Reproducing selectivities requires high accuracy in computing relative transition state energies. As demonstrated by the results summarized in this Account, this accuracy is possible with the use of the presented methodology, benefiting of course from a large extent of cancellation of systematic errors. It is argued that as the employed models become larger, the number of rotamers and isomers that have to be considered for every stationary point increases and a careful assessment of their energies is therefore necessary in order to ensure that the lowest energy conformation is located. This issue constitutes a bottleneck of the investigation in some cases and is particularly important when analyzing selectivities, since small energy differences need to be reproduced.

Triazole acetyl gold(III) catalyzed Meyer–Schuster rearrangement of propargyl alcohols

A new type triazole acetyl gold(III) was prepared and found to be an effective catalyst in Meyer–Schuster rearrangement of propargyl alcohols. The reactions proceeded well under much milder conditions to afford enones bearing a wide range of functional groups, thereby opening a new avenue for gold(III) catalysis. In addition, TriaAuCl2 catalyst was also effective on promotion of a-haloenones synthesis.

Study on the synthesis of the cyclopenta[f]indole core of raputindole A.

The raputindoles from the rutaceous tree Raputia simulans share a cyclopenta[f]indole partial structure the synthesis of which is subject of this investigation. An efficient route to a series of 1,5-di(indol-6-yl)pentenones was developed via Mo/Au-catalyzed Meyer–Schuster rearrangement of tertiary propargylic alcohol precursors. However, none of the enones underwent the desired Nazarov cyclization to a cyclopenta[f]indole. More suitable were 6-hydroxyallylated indolines which gave good yields of cyclopenta[f]indolines after treatment with SnCl4, as soon as sterically demanding β-cyclocitral adducts were reacted. Most successful were Pt(II) and Au(I)-catalyzed cyclizations of N-TIPS-protected indolin-6-yl-substituted propargylacetates which provided the hydrogenated tricyclic cyclopenta[f]indole core system in high yield.

ChemInform Abstract: Gold(I)/(III)‐Catalyzed Synthesis of 2‐Substituted Piperidines; Valency‐Controlled Cyclization Modes.

AbstractDepending on the catalyst propargylic alcohols (I) undergo either Meyer—Schuster rearrangement followed by aza‐Michael addition to give piperidines (II) or undergo direct cyclization to form alkynylated piperidines (III).

DDQ-Mediated Oxidative Radical Cycloisomerization of 1,5-Diynols: Regioselective Synthesis of Benzo[b]fluorenones under Metal-Free Conditions.

A regio- and chemoselective oxidative cycloisomerization reaction of acyclic 1,5-diynols has been developed. The reaction proceeds under metal-free reaction conditions with high efficiency and broad functional group tolerance, which offers a general and straightforward access to benzo[b]fluorenones under metal-free conditions. The preliminary mechanistic studies revealed the possible involvement of a Meyer-Schuster rearrangement combined with an oxidative radical cyclization.

Cross-Coupling of Meyer-Schuster Intermediates under Dual Gold-Photoredox Catalysis.

Under dual gold/photoredox catalytic conditions, intermediates from the Meyer-Schuster rearrangement underwent an efficient cross-coupling with arene diazonium salts, leading to α-arylated enones. Diazonium salts assisted the dissociation of the propargyl hydroxyl group by forming alkoxydiazenes in the Meyer-Schuster rearrangement, and the coupling was proposed to proceed through an allenyl methyl ether.

ChemInform Abstract: Mild Approach to 2‐Acylfurans via Intercepted Meyer—Schuster Rearrangement of 6‐Hydroxyhex‐2‐en‐4‐ynals.

AbstractThe protocol includes addition of 2 nucleophiles during the Meyer—Schuster rearrangement and allows the preparation of a broad spectrum of furan structures, anellated with an alicyclic ring.

The Z-enoate assisted, Meyer-Schuster rearrangement cascade: unconventional synthesis of α-arylenone esters.

Brønsted acid promoted nucleophilation of propargylic alcohols during the Meyer-Schuster rearrangement (M-S) has been introduced. A novel concept of reverse polarization of the M-S intermediate allenyl cation has been realized by employing a cis-enoate assisted strategy. This idea is well demonstrated by the metal free synthesis of complex, highly functionalized cyclic as well as acyclic α-arylenones. The synthetic importance of the derived products was highlighted by the efficient conversion to biologically relevant molecules such as pyrazoles and 4,5-seco-abietane.

BF3·OEt2-mediated syn-selective Meyer-Schuster rearrangement of phenoxy propargyl alcohols for Z-β-aryl-α,β-unsaturated esters.

Synthesis of Z-β-aryl-α,β-unsaturated esters from readily available 1-aryl-3-phenoxy propargyl alcohols is achieved via a BF3-mediated syn-selective Meyer-Schuster rearrangement under ambient conditions. The reaction mechanism is postulated to involve an electrophilic borylation of an allene intermediate as the key step to kinetically control the stereoselectivity.

Synthesis of α,β-Unsaturated Acylsilanes via Perrhenate-Catalyzed Meyer-Schuster Rearrangement of 1-Silylalkyn-3-ols.

We report the synthesis of α,β-unsaturated acylsilanes via the perrhenate-catalyzed Meyer-Schuster rearrangement of 1-silylalkyn-3-ols. Propargylic alcohols derived from TES-acetylene and substituted benzaldehydes can be converted to acylsilanes using a combination of p-TSA·H(2)O and n-Bu(4)N·ReO(4), or Ph(3)SiOReO(3) in good yields. Some propargylic alcohols derived from ketones, as well as aliphatic and unsaturated aldehydes, can also be converted to acylsilanes; however, they were often prone to side reactions.

ChemInform Abstract: An Intramolecular, Pd‐Mediated α‐Arylation Route to 4‐Aryl‐2‐naphthols.

AbstractThe short route to the title compounds (V) involves Meyer—Schuster rearrangement of butynol (III) followed by intramolecular α‐arylation.