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

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• blumiolide C was accomplished in an overall yield of 0.63%. In 2005, Hiersemann and co-workers reported an approach towards the synthesis of xeniolide F [13] employing a catalytic asymmetric Claisen rearrangement to set the crucial stereocenters at the C2 and C3 positions (Scheme 10) [54]. The synthesis

• rhodium carbenoid derived from diazophosphonoacetate 100 and alcohol 99 afforded intermediate 101 which was treated with lithium diisopropylamide and aldehyde 102 to afford alkene 103 with high E-selectivity. The following asymmetric copper(II)-catalyzed Claisen rearrangement [55], which is postulated to

• synthesized in four steps. Esterification with (R)-(+)-citronellic acid (127) yielded a single diastereomer of ester 128. Addition of lithium diisopropylamide to a mixture of 128, trimethylsilyl chloride and triethylamine initiated an Ireland–Claisen rearrangement [63] which gave carboxylic acid 129 in 85

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• cytotoxicity against a number of tumour cell lines. Keywords: modified Claisen rearrangement; sesquiterpene; chromenol; total synthesis; Introduction The panicein family is an unusual family of natural products, which generally consist of an aromatic sesquiterpene group linked to a quinone (as seen in

• its deacetylation product 20. The direct conversion of deacetylated product 20 to panicein A2 (5) through a modified Claisen rearrangement [19][20] was then attempted. Unfortunately, after heating 20 in toluene for 48 hours, no desired product 5 was obtained, with a complex mixture of compounds

• sesquiterpine panicein A2 (5) has been achieved. This synthesis hinges on key steps involving the addition of phenol 16 to carbonate 18 to provide propargyl ether 8 which was then cyclised through a modified Claisen rearrangement to ultimately give the desired cyclic structure of 5. The correlation of

Influence of bulky yet flexible N-heterocyclic carbene ligands in gold catalysis

• Alba Collado,
• Scott R. Patrick,
• Danila Gasperini,
• Sebastien Meiries and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 1809–1814, doi:10.3762/bjoc.11.196

• catalytic activity of complexes 7–9 in the synthesis of homoallylic ketones via hydroalkoxylation/Claisen rearrangement [61][62]. [Au(NHC)(NTf2)] complexes have proven to be efficient catalysts for this transformation, promoting the reaction under neat conditions and low catalyst loadings [61]. The

Spiro annulation of cage polycycles via Grignard reaction and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Mohammad Saifuddin,
• Rashid Ali and
• Gaddamedi Sreevani

Beilstein J. Org. Chem. 2015, 11, 1367–1372, doi:10.3762/bjoc.11.147

• Claisen rearrangement and RCM as key steps [21][30]. Here, we have prepared the cage dione 10 by the known route involving two atom-economic protocols such as Diels–Alder reaction and [2 + 2] photocycloaddition [42][43][44][45] (Scheme 1). Later, the hexacyclic cage dione 10 was subjected to a Grignard

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• [15]. The 11-step synthesis of icaritin, starting from 2,4,6-trihydroxyacetophenone via microwave-assisted Claisen rearrangement reaction as the key step, was succeeded with an overall yield of 23% [16]. In view of the long synthetic routes, tedious work-up and harsh reaction conditions, an

• , whose all hydroxy groups were protected for the rearrangement accompanied in the next step. It is noticeable that this compound is slightly less stable in solution, easily decomposing into 7 and 11 (Scheme 2), especially under acidic conditions. The Claisen rearrangement is commonly accepted as an

• gave an intractable product mixture, probably due to the prevalence of the 5-O-prenyl chain elimination with no rearrangement. Then we turned to try the latter method with 10 mol % Eu(fod)3 as the catalyst at 60 °C in dry CHCl3 (Table 1), in which the Claisen rearrangement of 8 indeed took place

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• -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. Keywords: allylation; cascade reactions; indigo

• ). The structure, including relative stereochemistry, was confirmed by X-ray crystallographic analysis. This compound was formed presumably after initial 9-membered ring production to give 30 in a typical ring-closing metathesis reaction, followed by an intramolecular Claisen rearrangement. Attempts to

• induce a similar Claisen rearrangement starting from the original spiro compound 12 by heating a DMF solution from 40 °C to 110 °C failed, with only decomposition being observed at the higher temperatures. This suggests that the Claisen rearrangement is being catalysed by the Ru present from the Grubbs

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• phenanthridine core starting from a simple disubstituted aniline relied on the aza-Claisen rearrangement, ring-closing enyne metathesis and Diels–Alder reaction [41] (Scheme 18). The obtained phenanthridine derivatives were polysubstituted at the phenyl side-rings, while retaining the unsubstituted central

• heterocyclic double bond. The diversity of the aza-Claisen rearrangement allows the application of this approach to other related heterocyclic systems. The preparation of a new variety of analogues, namely 6-phosphorylated phenanthridines was very recently reported, whereby central-ring cyclisation was

Design and synthesis of novel bis-annulated caged polycycles via ring-closing metathesis: pushpakenediol

• Sambasivarao Kotha and
• Mirtunjay Kumar Dipak

Beilstein J. Org. Chem. 2014, 10, 2664–2670, doi:10.3762/bjoc.10.280

• using the RCM protocol. To this end, we began with the Claisen rearrangement of bis(allyloxy)benzene 15 to deliver the two possible rearranged diallylated products 16 and 17 [29][30] in equimolar ratio. When 2,5-diallyl-1,4-hydroquinone (17) was subjected to MnO2 oxidation in acetone at room temperature

• Sambasivarao Kotha Mirtunjay Kumar Dipak Department of Chemistry, Indian Institute of Technology-Bombay, Powai, India, Fax: 022-2572 7152 10.3762/bjoc.10.280 Abstract Intricate caged molecular frameworks are assembled by an atom economical process via a Diels–Alder (DA) reaction, a Claisen

• rearrangement, a ring-closing metathesis (RCM) and an alkenyl Grignard addition. The introduction of olefinic moieties in the pentacycloundecane (PCUD) framework at appropriate positions followed by RCM led to the formation of novel heptacyclic cage systems. Keywords: Diels–Alder cycloaddition; Grignard

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson–Claisen rearrangement, asymmetric Mukaiyama aldol reaction and MNBA-mediated lactonization. Keywords: aldol reaction; astakolactin; lactonization; MNBA; terpenoids; Introduction

• constructed via an aldol reaction with ethyl acetate, followed by anti-selective methylation [32][33]. The trisubstituted alkene moiety of the prenyl chain of 3 could be stereoselectively constructed via a Johnson orthoester–Claisen rearrangement of 4 [34][35][36], which would be generated from compound 5

• group in the resulting diol 15 gave the monoprotected alcohol 16. This alcohol was then subjected to the Johnson orthoester–Claisen rearrangement, yielding only the (Z)-isomer 17 [36] in satisfactory yield. After the reduction of 17, the resulting aldehyde 18 was subjected to the aldol reaction with

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• family Dictyotaceae and from the sea hare [74][75]. Paquette and co-workers reported the first and only total synthesis of this diterpene (Figure 4) [41][42]. The cyclooctanoid core of the target was envisioned to be formed by a Claisen rearrangement of intermediate 81. The latter and most of its

• tetrahydropyran 92 as key intermediate of the synthesis. Oxidation of 92 and heating to 220 ºC resulted in a concurrent selenoxide elimination and Claisen rearrangement to give 93 via intermediate 81. Face-selective Simmons–Smith cyclopropanation, reduction of both carbonyl groups, and chemoselective oxidation of

Investigations of thiol-modified phenol derivatives for the use in thiol–ene photopolymerizations

• Sebastian Reinelt,
• Monir Tabatabai,
• Urs Karl Fischer,
• Norbert Moszner,
• Andreas Utterodt and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1733–1740, doi:10.3762/bjoc.10.180

• such as sodium hydride and allyl bromide (6), which resulted in the formation of the tetra-allyl (7a) and hexa-allyl (7b) derivatives (Scheme 1). The second route for the synthesis of the allyl-modified precursors (12a–c, 15) proceeded via Claisen rearrangement of the allylaryl ethers and subsequent

• initiated after 120 s. Synthetic route for the preparation of the thiol-functionalized bisphenols 10a and 10b. Synthetic route for the preparation of thiol-functionalized phenol derivatives 14a–c and 17 using the Claisen rearrangement and the radical addition of thioacetic acid as key steps. Chemical

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• framework of B-seco limonoid natural products by means of a [3,3]-sigmatropic rearrangement are described. Detailed model studies reveal, that an Ireland–Claisen rearrangement can be employed to construct the central C9–C10 bond thereby giving access to the B-seco limonoid scaffold. However, application of

• the developed strategy ended up failing in more complex and sterically demanding systems. Keywords: B-seco limonoids; biology oriented synthesis; Ireland–Claisen rearrangement; natural products; tetranortriterpenoids; Introduction B-seco limonoids are a family of more than 100 highly oxygenated

• : Claisen rearrangement. In planning the synthesis we were inspired by Ley’s synthesis of azadirachtin in which a Claisen rearrangement has been successfully employed as key transformation [37][38]. Thus the allyl vinyl ether rearrangement precursor 11 was thought to be obtained from an O-alkylation between

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• , reduction of the remaining double bond and subsequent Krapcho decarboxylation [132] resulted in less functionalized ketone 150. Aldol condensation with furfural followed by O-allylation and Claisen rearrangement furnished enone 151. Standard functional group interconversiones were used to access TIPS

• signature oxetane moiety. Ether cleavage [144] and Swern oxidation resulted in the formation of ketone 169. HWE-olefination followed by reduction to the allyl alcohol led to allylic ester 170 after a Johnson–Claisen rearrangement [145] upon treatment with triethyl orthoacetate. Ester 170 was saponificated

• to give pentacycle 172. Reduction of the nitro group was followed by Cbz-protection. Allylic alcohol 173 resulted from radical allylic bromination followed by displacement of bromine through water under silver-catalysis. Eschenmoser–Claisen rearrangement [148] led to the formation of the remaining

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

• Peter A. Wade,
• Alma Pipic,
• Matthias Zeller and
• Panagiota Tsetsakos

Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251

• ) to γ,δ-unsaturated nitro compounds. In the reported examples, 6-membered cyclic O-allyl nitronates were converted to 4-nitrocyclohexenes [1][2]. This rearrangement strongly resembles the classic Claisen rearrangement of allyl vinyl ethers [3][4][5][6]. The O-allyl nitronic ester rearrangement has

• methyl substituents at C(V) and C(VI) whereas other nitronic esters that do undergo rearrangement possess methyl or alkyl substituents at these positions. The absence of a methyl substituent in 4–7 at C(VI) is a likely contributing cause of failed rearrangement. In the Claisen rearrangement, a methyl

• general transition state 29. Negative charge in transition state 29 should be stabilized by a W-group at C(I). Substantial partial charge development would seem to be present from the observed results. In contrast, a W-group attached at C(I) of an allyl vinyl ether slightly decelerates a Claisen

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• reproducible yields than either the commercially available Grignard reagent or the organocerium. Johnson–Claisen rearrangement [50] of 44 proceeded smoothly to give the γ,δ-unsaturated ester 45. Conducting the reaction without added solvent in a microwave reactor at 170 °C allowed the reaction to proceed in

• olefin would interfere with dithiane coupling. However, given the suitability of the Claisen rearrangement for formation of this bond, we wished to preserve that transformation. Accordingly, an alternate route that would capitalize on the electrophilic nature of aldehyde 47 to form the bond corresponding

• changes in reductive couplings of alkynes and 3-oxygenated epoxides. Enyne reductive coupling with 1,2-epoxyoctane. Synthesis of dithiane by Claisen rearrangement. Deuterium labeling reveals that the allylic/benzylic site is most acidic. Oxy-Michael addition to δ-hydroxy-α,β-enones. Synthesis of

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• of vinylmagnesium bromide [16], provided 9. The bromoetherification of tertiary alcohol 9 by using NBS led to tetrahydrofuran 10 as a diastereomeric mixture. Next, the base-induced elimination of HBr converted 10 to diene 11, which underwent the Claisen rearrangement at 170 °C to give rise to

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• exceedingly potent Claisen rearrangement [37], with the attending advantages of stereocontrol and chirality transfer. Another powerful approach to polycyclic structures is through association with Robinson-type annelations [38]. The synthesis of the precursors also exploits the Claisen rearrangement, as shown

• diquinane intermediate 87 [38]. In all of these transformations, the chiral information residing in the starting allylic alcohol 80 is transmitted, through the Claisen rearrangement, to various other centres (the ratios in Scheme 17 and following schemes refer to ratios of diastereoisomers). Very recently

• tricyclic structure 93. In this sequence too, the chirality present in the starting material 89 is initially derived from an allylic alcohol by the Claisen rearrangement and is then transmitted to the other centres. Another powerful reaction that can be associated with the radical chemistry of xanthates is

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• ]. A wide variety of ynamides and organozinc reagents could be used for the reaction (Table 2). Yorimitsu and Oshima reported an interesting transformation of ynamides to nitriles by a carbomagnesiation/aza-Claisen rearrangement sequence (Scheme 15) [79][80]. Carbomagnesiation and carbozincation of

• aza-Claisen rearrangement. Uncatalyzed carbomagnesiation of cyclopropenes. Iron-catalyzed carbometalation of cyclopropenes. Enantioselective carbozincation of cyclopropenes. Copper-catalyzed facially selective carbomagnesiation. Arylmagnesiation of cyclopropenes. Enantioselective methylmagnesiation of

A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

• Mukund G. Kulkarni,
• Mayur P. Desai,
• Deekshaputra R. Birhade,
• Yunus B. Shaikh,
• Ajit N. Dhatrak and
• Ramesh Gannimani

Beilstein J. Org. Chem. 2012, 8, 1725–1729, doi:10.3762/bjoc.8.197

• important 3-methylquinoline-4-carbaldehydes 6a–h from o-nitrobenzaldehydes 1a–h employing a Wittig-olefination–Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a–h, which on heating under reflux in xylene

• underwent Claisen rearrangement to give 4-pentenals 3a–h. Protection of the aldehyde group of the 4-pentenals as acetals 4a–h and subsequent oxidative cleavage of the terminal olefin furnished nitroaldehydes 5a–h. Reductive cyclization of these nitroaldehydes yielded the required 3-methylquinoline-4

• -carbaldehydes 6a–h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure. Keywords: acetal; Claisen rearrangement; oxidative cleavage; ring-closure; Wittig olefination; Introduction

Alkoxide-induced ring opening of bicyclic 2-vinylcyclobutanones: A convenient synthesis of 2-vinyl-substituted 3-cycloalkene-1-carboxylic acid esters

• Xiufang Ji,
• Zhiming Li,
• Quanrui Wang and
• Andreas Goeke

Beilstein J. Org. Chem. 2012, 8, 650–657, doi:10.3762/bjoc.8.72

• or acid derivatives makes this transformation a good supplementary method for the well-established Johnson–Claisen rearrangement. Keywords: alkoxide; cyclobutanones; esters; fused ring systems; ring opening; Introduction A great variety of methods are available for the synthesis of cyclobutane

• proceeds by a two-step process, involving an initial hetero Diels–Alder cycloaddition of the diene and the ketene carbonyl group, followed by a [3,3]-sigmatropic (Claisen) rearrangement [25][26]. The most effective conditions were achieved by the employment of a slightly excessive amount of olefins 1. The

• conditions. Furthermore, the products have a general γ,δ-unsaturated carbonyl skeleton, and hence the protocol should be a good surrogate for the well-established Johnson orthoester Claisen rearrangement [28][29]. Determination of the structure of 3-phenyl-2-vinyl substituted cyclobutanone 4g. Metathetic

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• by chelated enolate Claisen rearrangement [22][23] or transition metal-catalyzed allylic alkylation of chelated enolates [24] and subsequent oxidative cleavage of the γ–δ-unsaturated amino acids obtained. Results and Discussion An alternative approach is based on regioselective ring opening of