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The enantioselective total synthesis of (–)-stemoamide using Overman/Claisen rearrangement of an allylic 1,2-diol is reported. The enantiopure allylic 1,2-diol was efficiently prepared from naturally occurring dimethyl tartrate. The chirality transfer reactions through two consecutive [3,3]-sigmatropic rearrangements proceeded with complete diastereoselectivity in a one-pot process.

A new method to synthesize γ,δ-unsaturated α-nitrogenated aldehydes in very good yields is described herein. This method involves a copper-coupling reaction between β-iodoenamide derivatives and allylic alcohols to generate β-allyloxyenamide derivatives. The latter, when heated, undergo a Claisen rearrangement and form γ,δ-unsaturated α-nitrogenated aldehydes.

A simple alternative method to 2,3-diallyl-1,4-quinone derivatives via a one-pot double claisen rearrangement and retro Diels—Alder reaction sequence involving readily available starting materials is reported.

The synthesis of 2-allenyl-2-substituted-3,3-difluoroindolines has been accomplished, taking advantage of the reaction between N-allenyl-indoles and Selectfluor under iron catalysis.

Described herein is the use of copper triflate to efficiently catalyze a [3+2] annulation of propargylic acetates with N-alkylanilines in the presence of trimethylsilyl chloride (Me3SiCl) to produce 2,3-disubstituted indole derivatives. Also, the copper(II) catalyst efficiently promoted an aza-Claisen rearrangement of N-arylated propargylic amines involving a 3-aza-1,5-enyne skeleton.

A novel protocol has been successfully established for the efficient synthesis of benzothiazole-tethered chromanone/coumarin scaffolds via Claisen rearrangement using a solid state melt reaction in a one-pot manner. Benzothiazole formation and Claisen rearrangement involve the cleavage of S–S and C–O bonds and formation of C–S, C═N, and C–C bonds in a single operation without using a catalyst or solvent.

The amide enolate-induced aza-Claisen rearrangement of the vinylazacycles furnishes 11- to 13-membered macrolactams with an internal (E)-olefinic bond, not accessible by conventional methods.

An efficient reductive Claisen rearrangement, catalyzed by in situ generated copper hydride and stoichiometric in diethoxymethylsilane, has been developed. Yields of up to 95 % with good to excellent diastereoselectivities were observed in this reaction. Mechanistic studies showed that the stereospecific rearrangement proceeded via a chair transition state of (E)-silyl ketene acetals as intermediates and not via the copper enolates.

The asymmetric propargyl Claisen rearrangement provides a convenient entry to chiral allene motifs. Herein, we describe the development of a kinetic resolution and asymmetric rearrangement of racemic propargyl vinyl ethers. This transformation afforded chiral allene products along with the enantiomerically enriched substrate in good yields with excellent diastereo- and enantioselectivity. The complete chirality transfer and facially selective rearrangement enabled the simultaneous construction of an axially chiral allenic unit and a quaternary carbon stereocenter.

A convenient protocol for the synthesis of natural isoprenoid-derived carboxylic esters via reaction of allylic terpenols with triethyl orthoacetate (propionate) in the presence of 1-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF6] (10 mol%), has been developed. The desired terpene derivatives were prepared in moderate to high yield. The ionic liquid (IL) can be easily separated from the products and repeatedly used up to ten times without reduction in the product yield. Experimental data evidence that HF, generated in situ from the IL, most likely acts as a true catalyst in the Johnson–Claisen rearrangement.

Allyl, dimethylallyl, crotyl, and prenyl ethers of various aromatic ortho-hydroxy carbonyl compounds undergo a tandem sequence of Claisen rearrangement, carbonyl olefination, and cyclization upon microwave irradiation in the presence of a stabilized ylide. The products are multiply substituted 6- or 8-allylated or prenylated coumarins (2H-chromen-2-ones).

The microwave-assisted imidazole-catalyzed transformation of propargyl vinyl ethers (PVEs) into multisubstituted salicylaldehydes is described. The reaction is instrumentally simple, scalable, and tolerates a diverse degree of substitution at the propargylic position of the starting PVE. The generated salicylaldehyde motifs incorporate a broad range of topologies, spanning from simple aromatic monocycles to complex fused polycyclic systems. The reaction is highly regioselective and takes place under symmetry-breaking conditions. The preparative power of this reaction was demonstrated in the first total synthesis of morintrifolin B, a benzophenone metabolite isolated from the small tree Morinda citrifolia L. A DFT study of the reaction was performed with full agreement between calculated values and experimental results. The theoretically calculated values support a domino mechanism comprising a propargyl Claisen rearrangement, a [1,3]-H shift, a [1,7]-H shift (enolization), a 6π electrocyclization, and an aromatization reaction.

The synthesis of vinyl boronates and vinyl silanes was achieved by employing a Ru-catalyzed alkene-alkyne coupling reaction of allyl boronates or allyl silanes with various alkynes. The double bond geometry in the generated vinyl boronates can be remotely controlled by the juxtaposing boron- and silicon groups on the alkyne substrate. The synthetic utility of the coupling products has been demonstrated in a variety of synthetic transformations, including iterative cross-coupling reactions, and a Chan-Lam-type allyloxylation followed by a Claisen rearrangement. A sequential one-pot alkene-alkyne-coupling/allylation-sequence with an aldehyde to deliver a highly complex α-silyl-β-hydroxy olefin with a handle for further functionalization was also realized.

The decomposition of diazo compounds in the presence of N-allylanilines and rare-earth metal triflates involves a [3,3]-sigmatropic rearrangement of the intermediate ylide with migration of the allyl substituent to an ortho position of the aromatic ring, whereas thermal decomposition without using rare-earth metal triflates occurs through a [2,3]-sigmatropic rearrangement with migration of the allyl moiety to the ylide centre (VIII).

Allyl, dimethylallyl, and prenyl ethers of ortho-acylphenols react upon microwave irradiation to form C-allylated or -prenylated chromones.

Quaternary centers are rapidly and selectively installed in a series of seven-membered and bridged cyclic oxonitriles through conjugate addition of an alkoxide to chloroalkenenitriles, followed by a Claisen rearrangement. Using this strategy, the stereogenic information of the carbinol in secondary allylic alcohols is transferred to the newly generated quaternary center. Experimentally, the sequence rapidly gives alkyl cyanocycloheptanones and bicycloalkanonecarbonitriles in good yield and with high selectivity, in a single synthetic operation.

An NBS-promoted allyloxyl addition–Claisen rearrangement–dehydrobromination cascade reaction has been developed. More than 20 substituted alkynylsulfonamides were reacted with allyl alcohols to generate (2Z)-2,4-dienamides in moderate to high yields. A mechanistic model has been proposed to account for the overall reaction sequence including the stereochemical outcome. Theoretical calculations suggested that a [3,3] sigmatropic rearrangement be the rate-limiting step.

A convenient and simple method for the synthesis of novel 3,4-dihydrofuran-annulated coumarins, 3-(hydroxymethyl)-2H-furo[3,2-c]chromen-4(3H)-ones 5a, 5b, 5c, 5d, 5e, 5f, 5g, by combined Claisen rearrangement and intramolecular regioselective oxidative cyclization of 4-O-allyl coumarin intermediates 3a, 3b, 3c, 3d, 3e, 3f, 3g using inexpensive oxidizing agent m-CPBA is described. The reaction proceeds smoothly by tandem epoxidation/regioselective 5-exo-tet-intramolecular ring opening. The structures of synthesized compounds are established on the basis of spectral data including IR, 1H NMR, and mass and elemental analyses.

An enantioselective alkoxylation/Claisen rearrangement reaction was achieved by a strategic desymmetrization of 1,4-dienes under the catalysis of (S)-DTBM-Segphos(AuCl)2/AgBF4. This reaction system was highly selective for the formation of 3,3-rearrangement products, providing cycloheptenes with various substitutions in good yield and good to excellent enantioselectivity. This transformation was further extended to bicyclic ring substrates, providing the opportunity to easily assemble 5,6- and 6,7-fused ring systems.

A short and efficient synthesis of (+)-subersic acid in 6 steps with an overall yield of 8.6% from (−)-Sclareol was presented using Mitsunobu reaction and Claisen rearrangement as critical steps. This elegant protocol gave a convenient access to gram scales of (+)-subersic acid, which could be a precursor for its structural analogues and for further bioactivity researches.

Chromone-3-ylmethyl aryl ethers (I) undergo a novel domino [1,3]-[1,3]-rearrangement to give 4′-hydroxyhomoisoflavones (II) under thermal conditions whereas, the para-substituted ethers (IV) lead to 2′-hydroxyhomoisoflavones instead of the expected Claisen rearrangement.

The Claisen rearrangement is an ideal candidate for mechanistic and transition-state analysis. Recently, physical-chemistry investigations, in particular relying on quantum mechanics and modern fs-pulse (‘short-time') laser spectroscopy, have given totally new insights here. At the same time, flow chemistry has emerged, offering considerable processing advances over batch processing. It is also known to be much powerful with inline flow sensing techniques. Yet, both key innovations have not been bridged so far and thus there is an eminent knowledge gap in mechanistic analysis of reactions. This two-review compilation is a first step to close this gap. Part 1 focuses on the insight which quantum-mechanical calculations can add to the existing knowledge based on heuristic, handy interpretation of reaction experiments in the light of electrodensity distributions. Quantum-mechanical calculation can provide geometric key data and short-time laser spectroscopy can verify this and deepen it in the sense of a comprehensive vibration analysis. In this way, prior structural assumptions can be confirmed or turned to be falsified and there is potential to resolve the uncertainty.

Diversity-directed synthesis based on the cascade allylation chemistry of indigo, with its embedded 2,2’-diindolic core, has resulted in rapid access to new examples of the hydroxy-8a,13-dihydroazepino[1,2-a:3,4-b']diindol-14(8H)-one skeleton in up to 51% yield. Additionally a derivative of the novel bridged heterocycle 7,8-dihydro-6H-6,8a-epoxyazepino[1,2-a:3,4-b']diindol-14(13H)-one was produced when the olefin of the allylic substrate was terminally disubstituted. Further optimisation also produced viable one-pot syntheses of derivatives of the spiro(indoline-2,9'-pyrido[1,2-a]indol)-3-one (65%) and pyrido[1,2,3-s,t]indolo[1,2-a]azepino[3,4-b]indol-17-one (72%) heterocyclic systems. Ring-closing metathesis of the N,O-diallylic spiro structure and subsequent Claisen rearrangement gave rise to the new (1R,8aS,17aS)-rel-1,2-dihydro-1-vinyl-8H,17H,9H-benz[2',3']pyrrolizino[1',7a':2,3]pyrido[1,2-a]indole-8,17-(2H,9H)-dione heterocyclic system.

A new protocol based on sequential applications of three atom-economic processes viz. Claisen rearrangement, olefin isomerisation, and ring-closing diene metathesis has been developed to access a range of linear and angularly fused pyranocoumarin derivatives. Incorporation of enyne (in place of diene) metathesis and Diels–Alder reaction in the sequence has allowed the corresponding benzannulated derivatives to be prepared in good yields.

Allyl phenyl ethers with a pendant enone substituent undergo, upon microwave irradiation, a domino sequence of Claisen rearrangement and 6-endo-trig-cyclization to furnish functionalized chroman-4-ones. The natural products tabchromones A and B were synthesized via this method.

The generation of highly substituted furans from propargyl vinyl ethers bearing a free hydroxy group was investigated. In the presence of catalytic amounts of AgBF4, a formal [3,3] sigmatropic rearrangement takes place in the first stage of the sequence. The resulting allenyl carbonyl intermediates then undergo cyclocondensation, which upon double-bond isomerization leads directly to the five-membered heterocyclic products. This domino reaction allows the synthesis of various tri- and tetrasubstituted furan products; an example leading to pyrroles in an analogous way is also described.

A facile double allylation/ring-closing metathesis/Claisen rearrangement route for preparing vinylcyclopropanes 6 is developed. The efficient synthesis includes O-allylation of α-allyl-α-sulfonylketones 8 with allylic bromides, ring-closing metathesis of diallyl compounds 9 and sequential Claisen rearrangement of the resulting oxepines.

This is a highly efficient Ni(II)-catalyzed Claisen rearrangement of a variety of both propargyl and allyl vinyl ethers using a chiral N,N-dioxide as ligand.

Homoallylic ketones combine arguably two of the most synthetically useful functional groups in organic chemistry and are, therefore, very valuable synthetic intermediates. General methods for the synthesis of these intermediates include the allylation of carbonyl compounds via π-allyl palladium(II) complexes,[1] the 1,4-addition of vinylmetal nucleophiles onto α,β-unsaturated compounds,[2] and the Claisen rearrangement of allyl vinyl ethers (Scheme 1).[3] The control of the regioselectivity in the latter procedure can be achieved by a domino process consisting of a copper-catalyzed C–O bond coupling of alkenyl iodides with allylic alcohols, followed by sigmatropic rearrangement.[4] Scheme 1 General methods for the synthesis of homoallylic ketones. NPhth=Phthalimide. The synthetic equivalence of acetylenes with carbonyl compounds was first recognized in this context by the group of Trost who found that homoallylic ketones could be obtained by the RuII-catalyzed addition of allyl alcohols to terminal alkynes, in a process that probably took place by means of the cycloaddition of both unsaturated substrates to form a ruthenacyclopentene intermediate.[5] In the last decade, cationic gold(I) complexes have emerged as the most reactive catalysts for the activation of alkynes towards the nucleophilic addition of a wide range of hetero- and carbonucleophiles.[6] Although the first synthetically useful applications of homogeneous gold catalysis in organic synthesis involved the attack of alcohols onto alkynes,[7] it was not until 2013 that a method for the preparation of allyl vinyl ethers based on this process was developed. This process was achieved by the group of Aponick, who developed a tandem intermolecular hydroalkoxylation/Claisen rearrangement (Scheme 2).[8] This new cascade reaction led to the direct formation of γ,δ-unsaturated ketones from simple starting materials in a single step and with excellent stereoselectivity in most cases. This transformation was performed by using 5 mol % of both neutral gold(I) complex [Au(Cl)(IPr)] (IPr=1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) and AgBF4, which was required to generate the gold(I) cationic species in situ. Scheme 2 Gold(I)-catalyzed synthesis of homoallylic ketones by hydroalkoxylation/Claisen rearrangement. In a step towards the development of a highly efficient synthesis of homoallylic ketones, the group of Nolan has pushed this method towards its limits by reducing the amount of gold(I) catalyst by an order of magnitude and by conducting the reaction in the absence of solvent, using a 1:3 alkyne to allyl alcohol ratio.[9] Importantly, by using [Au(NTf2)(IPrCl)] (Tf=triflate; IPrCl=4,5-dichloro-1,3-bis(2,6-diisopropylphenyl)-1H-imidazol-2-ylidene) as the catalyst, which proved to be robust enough to withstand the relatively harsh reaction conditions, the addition of a hygroscopic and light-sensitive silver salt was no longer necessary. By reducing the catalyst loading to 0.2–0.5 mol %, the new process took place with turnover numbers (TON) from 96 to 465 and turnover frequencies (TOF) from 6 to 1396 h−1. The regioselectivity of this process was largely controlled by the electronic nature of the alkyne substituents (Scheme 2).[8] Thus, the most electron-rich alkyne substituent (Scheme 2, blue) ended up at the ketone terminus, whereas the least electron-rich group (Scheme 2, green) became the α-substituent of the final ketone product. This result can be explained by the initial attack of the alcohol onto the alkyne gold(I) complex in a Markovnikov manner, hence by attack at the carbon bearing the most electron-rich group. The overall mechanistic scenario is reasonably well-understood and follows well-known principles in homogeneous gold(I) catalysis (Scheme 3).[8, 10] However, even with the assistance of high-level computations, no unambiguous conclusion could be drawn on whether the final step proceeded by simple thermal [3,3]-sigmatropic rearrangement, or if it was promoted by gold(I) through lowering of the activation energy by coordination to the enol ether oxygen. A direct [3,3]-sigmatropic rearrangement could also take place from the allyloxy vinylgold(I) intermediate to form a C–gold(I) ketone enolate, which would undergo protonolysis to give the final compounds. Regarding the observed diastereoselectivity, the major products resulted from a Claisen rearrangement proceeding through chair transition states.[8] Scheme 3 Catalytic cycle for the gold(I)-catalyzed synthesis of homoallylic ketones by hydroalkoxylation/Claisen rearrangement. One may legitimately wonder whether this process constitutes a significant improvement and if it is the most efficient synthesis of homoallylic ketones. From the point of view of catalytic efficiency and simplicity, the reaction discovered by Aponick is the best method for the synthesis of a wide variety of homoallylic ketones from inexpensive and commercially available materials. The further refinement by the group of Nolan is also an excellent example of green chemistry in chemical synthesis.[10] In particular, the demonstration that this process can be carried out efficiently under solvent-free conditions should encourage other groups to develop even more challenging processes, including cascade transformations, in the absence of solvent and with lower catalyst loadings than those usually employed in most gold(I)-catalyzed transformations. However, there are still some challenges to be met. Firstly, although in a number of examples the diastereoselectivity was good, lower diastereoselectivities were achieved with lower catalyst loadings. In addition, terminal alkynes were relatively poor substrates in this reaction, requiring 0.5 mol % catalyst and furnishing lower yields (48–77 %, five examples) even under optimized conditions.[9] Moreover, and assuming gold(I) catalyzes the final sigmatropic rearrangement, the development of an enantioselective synthesis of homoallylic ketones employing this method would present a formidable challenge. In this scenario, the gold(I) catalyst should act as a chiral Lewis acid in the enantio-discriminating Claisen rearrangement, and this would require overcoming the intrinsic limitation posed by the linear dicoordination of gold(I) complexes, which tends to place the chiral ligand far away from the reactive center.

Total syntheses of the spiro-epimeric natural products (–)-heliespirone A and (+)-heliespirone C are described. The successful strategy involved an aromatic Claisen rearrangement, a diastereoselective Sharpless asymmetric dihydroxylation (AD) reaction, and an intramolecular oxa-Michael addition.

The novel cascade reaction of amino enynes with azides allows the synthesis of a wide range of α-allylic amidines in high yields.

We herein report a mild method for the preparation of dihydrobenzofurans through hydrothermal catalytic tandem Claisen rearrangement–intramolecular hydroaryloxylation of allyl phenyl ethers. This reaction provides a new method for constructing dihydrobenzofurans, a process that is potentially applicable to natural product synthesis. SBA-15, TS-1, HZSM-5 were chosen as catalysts in a hydrothermal reaction medium between 200 and 320 °C. HZSM-5 catalyst showed the highest catalytic activity, and the effects of molar ratio of allyl phenyl ether–water, time, pressure, temperature and catalyst on the Claisen hydroaryloxylation in hydrothermal condition were investigated. The latter two process variables had the greatest influence on the product yields and distribution. A series of allyl phenyl ether derivatives were also treated in hydrothermal condition with HZSM-5 catalyst to offer high yield of corresponding dihydrobenzofurans.

Among numerous reactions to prepare cyclophane derivatives, Claisen rearrangement reaction is very useful. We have prepared cyclophanes containing ethylene oxy bridge by double Claisen rearrangement reaction and ring-closing metathesis reaction as key steps.

The asymmetric synthesis of (-)-dihydrosporothriolide (1), a biologically active bis-γ-butyrolactone, is described, that proceeds through a D-proline-catalyzed asymmetric aminooxylation, indium-mediated Reformatsky-Claisen rearrangement of an α,α-dibromoacetate derivative, and diastereoselective dihydroxylation. The route requires no protective group manipulation and allows the concise seven-step synthesis of 1 from n-octanal.

The role of commercially available Ammonium chloride in organic synthesis can not be understated. This review summarizes the versatile synthetic applications of Ammonium chloride in different chemical transformations. Reactions include Claisen rearrangement, Ullmann coupling, thia-Michael addition, three- component synthesis of dihydropyrimidinones, imidazo(1,2-a)pyridines, tetrahydrobenzo(a)xanthene-11-ones, benzoxazines, iminooxazolines, imidazo(1,2-a)pyrimidines, spirochromenes, spiroacridines, four-component synthesis of dipeptides, pyrrolo(3,4-b)pyridine-5-ones, crossed-aldol condensation, condensation of carbonyl compounds and indoles, synthesis of quinoxalines, arylbenzothiazoles, bisbenzothiazoles, reduction, and oxidation. Application of this catalyst allows mild and highly selective transformation and synthesis in a facile and environmentally friendly manner. Moreover, Ammonium chloride is an inexpensive and easily available catalyst, which acts under neutral conditons.

A stereoselective approach for the formation of 2,8-dioxabicyclo[3.3.1]nonane/nonene frameworks through the formation of 3-C-branched glycals encompassing the Claisen rearrangement of the carbohydrate-derived allyl-vinyl ethers and TMSOTf-catalyzed acetalization reactions as key steps is revealed. A novel acetalization of 3-C-branched glycals with a tentative mechanism is proposed. The expedient protocol is evaluated by synthesizing a number of 2,8-dioxabicyclo[3.3.1]nonane/nonene architectures.

The orthoester Johnson–Claisen rearrangement, an important C–C bond forming reaction, has been used enormously in the past four decades in the synthesis of bioactive molecules, natural products, synthetic intermediates, analogues, and useful building blocks. The method has also featured in chemical modification of materials. This review covers developments in this rearrangement since 2003. Unlike many other forms of Claisen rearrangement, this reaction is generally a one-pot, one-step process. It is compatible with numerous functional groups, despite its use of acid catalysis, and offers chirality transfer to produce stereoselective products. The method also offers opportunities for rapid modifications to various functionalized compounds and building blocks for further synthetic exploration.

It is demonstrated that terminal cyano-substituted 5-alkyn-1-ol systems serve as versatile precursors to a variety of cyclooctenone derivatives via one-pot base-catalyzed oxyanionic 6-exo dig cyclization/Claisen rearrangement sequence under microwave irradiation.

An efficient and scalable total synthesis of the architecturally challenging sesquiterpenoid (±)-penifulvin A has been accomplished via a 12-step sequence with an overall yield of 16%. For the construction of this structurally complex tetracyclic molecule, the key steps used included 1,4-conjugate addition, a Pd(0) catalyzed cross-coupling reaction between an enol phosphate and trimethyl aluminum, Claisen rearrangement using the Johnson orthoester protocol, Ti(III)-mediated reductive epoxide opening–cyclization, Lewis acid catalyzed epoxy-aldehyde rearrangement, and finally a substrate controlled oxidative cascade lactonization process.

A highly stereocontrolled, convergent total synthesis of kendomycin [(-)-TAN2162], an ansa-macrocyclic antibiotic, is reported. The key of the strategy is an unprecedented Tsuji-Trost macrocyclic etherification, followed by a transannular Claisen rearrangement to construct the 18-membered carbocyclic framework. The oxa-six- and five-membered rings were also stereoselectively constructed respectively by a cascade oxidative cyclization at an unfunctionalized benzylic position and using a one-pot epoxidation/5-exo-tet epoxide opening.

The enantioselective synthesis of (−)-9,10-dihydroecklonialactone B is described. The catalytic asymmetric Claisen rearrangement of a Gosteli-type allyl vinyl ether was utilized to afford an acyclic α-keto ester building block endowed with functionality amenable to the preparation of the carbocyclic target molecule by suitable postrearrangement transformations: A highly diastereoselective Corey–Bakshi–Shibata reduction of a β-chiral α-keto ester and a reductive homologation of an α-hydroxy ester. A transprotection tactic by a chemoselective intramolecular 6-exo-trig iodoetherification enabled regioselective ring-closing alkene metatheses to afford the 5- as well as the 14-membered ring, however, with mixed success in terms of E/Z selectivity.

Claisen rearrangement of bis-O-allylbiphenyl provides mixtures of honokiol (II) and isohonokiol (III) under both conventional and microwave heating conditions.

The precursors (I), (V), and (VIII) are prepared from the corresponding phenols by Claisen rearrangement.