Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• synthesis of spiro-annulated pyrrolidine-2,5-diones by catalyzed spirocyclizations involving aldehydes [11], tetrahydrofuran [12][13], and in the O–H insertion/Claisen rearrangement/intramolecular oxa-Michael addition cascade [14] (Scheme 1). Herein, we report our findings obtained, while investigating the

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• undergoes a Claisen rearrangement to afford the endo-isomer 112. Thermal isomerization of 113a by a 6π-electrocyclic ring-opening/closing cascade leads to the to the final exo-isomer 107. In 2018, the Zhang lab investigated the Ru-catalyzed ring-opening/dehydration of oxabicyclic alkenes 30 via the C–H

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• their anti-inflammatory activity (see Section 3). Reaction of compounds 166 and 167 gave the corresponding diaryl ether 168, which was converted to phenol 169 using a Baeyer–Villiger oxidation reaction followed by hydrolysis. Subsequent phenol allylation reaction followed by Claisen rearrangement led to

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• synthesis started from 3-hydroxy-2-methoxybenzaldehyde (34), which was converted into Grignard reagent 35 and added onto 3-methylbut-2-enal (Scheme 6). A sequence involving Claisen rearrangement, Roskamp homologation, diazo transfer and intramolecular cyclopropanation led to intermediate 37. The hydroxy

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• insertion of carbenes derived from diazo arylidene succinimides (DAS) into the O–H bond of phenols is described. The initial adducts underwent a thermally promoted Claisen rearrangement followed by DABCO-catalyzed intramolecular 5-exo-trig oxa-Michael addition. Keywords: Claisen rearrangement; diazo

• 50 °C for 12 h, underwent the Claisen rearrangement to give diastereomerically pure maleimide 4a in 4% yield [15]. While for our study at the time the formation of 3 and 4 were viewed as a minor side-reaction, later be started pondering the possibility of giving the observed transformation a stronger

• impetus from the synthetic point of view. Specifically, we wanted to see if Rh(II)-catalyzed insertion of DAS-derived carbenes could be performed into the O–H bond of phenols and if the resulting phenoxy-substituted succinimides 5 could also undergo a Claisen rearrangement. The products of the latter (6

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• temperature of the nanostructured particles (Figure 4B). The Claisen rearrangement of the electron-deficient aryl allyl ether 9 was chosen to compare the versatility and performance of inductive heating with conventional and microwave heating (Scheme 8A) [50]. The effectiveness of inductive heating is clearly

• at 110–160 bar to form the O-allyl phenol which was heated in a second reactor to 265 °C where the Claisen rearrangement under near-critical conditions occurred to yield 2-allyl-4,6-difluorophenol (12) in 64% yield. In this example, the two reactors made of steel were heated directly by the external

• three-component reaction (reaction 2) to propargyl amines 8 under continuous flow conditions with microwave assistance. Claisen rearrangement in flow: A. comparison between conventional heating (external oil bath), microwave irradiation, and inductive heating; and B. coupled flow-through protocol

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• Phil Servatius Uli Kazmaier Organic Chemistry, Saarland University, Campus C4.2, 66123 Saarbrücken, Germany 10.3762/bjoc.18.19 Abstract A peptide Claisen rearrangement is used as key step to generate a tetrapeptide with a C-terminal double unsaturated side chain. Activation and cyclization give

• , such as histone deacetylases. Keywords: chelated enolate; Claisen rearrangement; HDAC inhibitor; peptide; late stage modification; Introduction Among natural products, peptidic structures have entered the limelight due to their extraordinary biological activities [1]. Often found as secondary

• decided to take advantage of an asymmetric chelate enolate Claisen rearrangement, which should allow the stereoselective generation of the unusual amino acid, depending on the configuration of the chiral allylic alcohol used [41][42]. If a peptide Claisen rearrangement [43][44][45] is carried out with a

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• with diverse biological activities [17]. The key step first involved the rhodium carbenoid-mediated OH insertion/Claisen rearrangement following complexation of diazoester 56 and allylic alcohol 57 to produce intermediate 58 (Figure 13). Addition of BF3·OEt2 to the reaction mixture then catalyzed the α

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• in a 9:1 ratio. After chromatographic separation, alcohol (−)-77a, isolated in 67% yield and >99% de was subjected to a Claisen rearrangement, leading to aldehyde (−)-78 in 79% yield (96% de determined by 1H NMR). (−)-78 was treated with vinylmagnesium bromide to give a mixture of allyl alcohols

• , Spino et al. firstly made the quaternary center, followed by cyclization. Furthermore, Spino's synthesis involved key reactions such as Claisen rearrangement, olefin metathesis, and the Curtius rearrangement that allowed both natural products in good yields. Davis synthesis – 2010 Davis and Edupuganti

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• ] was followed by a 3-O-vinylation. A thermal 3,3-sigmatropic Claisen rearrangement of 62 gave the cis-2,6-disubstituted dihydropyran 63, which upon sequential Wittig olefination with 2-(triphenylphosporanylidene)propanal and then methylenetriphenylphosphorane yielded the diene 64. The removal of the di

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• Bratislava, Mlynská dolina, Ilkovičova 6, 84215 Bratislava, Slovakia 10.3762/bjoc.15.290 Abstract A range of chiral hydrogen-bond-donating organocatalysts was tested in the Ireland–Claisen rearrangement of silyl ketene acetals. None of these organocatalysts was able to impart any enantioselectivity on the

• rearrangements. Furthermore, these organocatalysts slowed down the Ireland–Claisen rearrangement in comparison to an uncatalyzed reaction. The catalyst-free reaction proceeded well in green solvents or without any solvent. DFT calculations showed that the activation barriers are higher for reactions involving

• rearrangement; silyl ketene acetals; Introduction The Ireland–Claisen rearrangement is a reaction converting allyl esters to γ,δ-unsaturated carboxylic acids. Its key step is a [3,3]-sigmatropic rearrangement of a silyl ketene acetal, which is generated in situ by deprotonation of an allyl ester using a strong

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• , which could readily be converted to triptolide and its relatives such as triptophenolid, tripdiolide, and 16-hydroxytriptolide via palladium-catalyzed cross-coupling or Claisen rearrangement reactions. Importantly, by modification of the C-2,C3 olefin and late-stage installation of the C-13 isopropyl

• the formal synthesis of triptolide (Figure 2, route N) [43]. This synthesis highlighted the palladium-catalyzed asymmetric addition of arylboronic acid 37 to 3-methylcyclohex-2-en-1-one (38) to form the C-10 quaternary chiral center, and a subsequent Claisen rearrangement and an aldol reaction to

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• . In most cases, the C2–C3 bond was formed by Ireland-, Johnson-, or Eschenmoser–Claisen rearrangement [10][11][12][13][14][15][16][17]. Alternatively, Evans methodology has been used [18][19][20]. The central C4–C5 double bond has also been constructed by Wittig reaction, cross metathesis, and ring

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• to access functionalized alkylidenecyclopropanes, with creation of a new carbon–carbon bond on the three-membered ring with the control of two contiguous stereocenters. Ireland–Claisen rearrangement of cyclopropenylcarbinyl esters The Ireland–Claisen rearrangement of silyl ketene acetals generated

• from allylic (or propargylic) esters is arguably one of the most useful variant of the Claisen rearrangement that has found countless applications in organic synthesis [59]. The feasibility of the Ireland–Claisen rearrangement of cyclopropenylcarbinyl esters was investigated in the case of glycolates

• %). That the Ireland–Claisen rearrangement of cyclopropenylcarbinyl glycolates proceeded with chirality transfer was also verified in the case of alkylidenecyclopropanes 58a and 58i which were obtained with optical purities (ee = 87% and ee = 97%, respectively) identical to those of the corresponding

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• Christiane Schultze Bernd Schmidt Universität Potsdam, Institut fuer Chemie, Karl-Liebknecht-Straße 24–25, D-14476 Potsdam-Golm, Germany 10.3762/bjoc.14.278 Abstract 8-Allylcoumarins are conveniently accessible through a microwave-promoted tandem Claisen rearrangement/Wittig olefination

• the past few years. Starting materials are allyl ethers of salicylic aldehydes or ketones 5 and the stable ylide ethyl (triphosphoranylidene)acetate (6), which upon microwave irradiation undergo a tandem Claisen rearrangement/Wittig olefination/cyclization sequence. This sequence was pioneered by the

• furnished the azepinocoumarin 21 in quantitative yield (Scheme 3). Conclusion In summary, we demonstrated that annellated coumarins become accessible from appropriately substituted benzene derivatives in few steps, using a microwave-promoted tandem Wittig olefination/Claisen rearrangement/cyclization

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• Diels–Alder reaction, Claisen rearrangement, cross-metathesis, and cross-enyne metathesis are used. The synergistic combination of these powerful reactions is found to be useful for the construction of complex targets and fulfill synthetic brevity. Keywords: Claisen rearrangement; Diels–Alder reaction

• , Claisen rearrangement (CR) of 77 under microwave irradiation (MWI) conditions on a silica gel support followed by O-allylation of the resulting CR product furnished diallyl compound 78. Treatment of diallyl compound 78 with G-I catalyst 1 delivered the expected naphthoxepine derivative 79 (96%). Next

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• congruence with the reductive iodonio-Claisen rearrangement (RICR) to show that there may be an underlying mechanism which expands the reasoning behind the previously known C–C bond-forming reaction. By rationalizing the hypervalent iodine’s metal-like properties it was concluded that a transmetallation

• -Claisen rearrangement (RICR) to describe the product selectivity they encountered [8]. More recently, exceptional progress has been made in investigating the RICR’s substrate scope (electron-donating versus electron-withdrawing substituents on PhI(OAc)2 (1a)), mechanism (deuterium labelling studies

• hypervalent iodine-guided electrophilic substitution (HIGES) reaction was discovered. The new reaction is thought to have some similarities to the reductive iodonio-Claisen rearrangement except that, with respect to the iodine, para-substituted instead of ortho-substituted products are mainly isolated. Future

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• formed as mixtures of (E)- and (Z)-isomers from SF5-substituted acetic acid esters of aliphatic terminal allylic alcohols at low temperature. At slightly elevated temperature, the latter diastereomers are transformed to γ,δ-unsaturated α-pentafluoro-λ6-sulfanyl alkanoic acids in an Ireland–Claisen

• rearrangement [31]. Under slightly modified conditions, this type of rearrangement was also successful for SF5-substituted acetic esters of cinnamyl alcohols [32]. Herein we describe our results [33] of highly syn-diastereoselective silicon Mukaiyama-type aldol reactions of SF5-acetic acid esters with different

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• was performed on 76a and monofluoroalkenes 77 were obtained in good yields and high selectivity. Claisen rearrangement and further modifications (hydrolysis of the trichloroacetoamide, Boc protection of the free amine, deprotection of the alcohol and Jones oxidation to give the carboxylic acid

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• could be functionalized by diverse alkene chemistry. We believe that a large number of molecules similar to (±)-5j can also be synthesized using diverse 2-allylphenols (which are easily accessible via the well-known Claisen rearrangement). Also, compound (±)-5l seems to have important synthetic

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• in Figure 2. At this point, we turned our attention to understand the configurational origin of the allyl groups in 2a. To understand whether compound 2a was formed by Claisen rearrangement (CR) of the corresponding O-allyl compound or by carbanion mediated C-allylation of the DA adduct 3a, we

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• construction of diverse fused ring systems. Other classical pericyclic processes that may potentially occur in fulvene fragments (electrocyclic and ene reactions, sigmatropic rearrangements and shifts) have received less attention, most probably with the only exception of the Claisen rearrangement [16

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• could be readily prepared from ortho-bromophenol (9, Scheme 2). O-Allylation of 9 followed by Lewis acid-mediated Claisen rearrangement afforded ortho-allylphenol 11, whose olefin moiety was ozonolyzed and subsequently treated with Wittig reagent 13 to provide amide 7 in 55% yield over four steps from 9