The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group introduced via the allene component is also variable and hence the subsequent transformation of this substituent into a hydroxy group can be performed under different conditions

• pattern of the allene – a remarkable variety of reactions and product types are known using the three-carbon backbone of these reactive compounds [10]. During the exploration of alkoxyallene chemistry [11][12][13][14][15][16][17][18][19][20] we accidently discovered a new three-component reaction leading

• corresponding Z-isomers occurs. It should be noted here that the protonation to the allenyl iminium species B implies an “umpolung of reactivity” of the alkoxyallene subunit converting the central allene carbon to an electrophilic center whereas this carbon is a nucleophilic center in the neutral compound. The

Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov,
• Olesya V. Khoroshilova and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2018, 14, 2897–2906, doi:10.3762/bjoc.14.268

• followed by acetylene–allene rearrangement was used to prepare (arylsulfinyl)allenes 1 according to the literature procedure [24][25]. The latter were in situ oxidized to (arylsulfonyl)allenes 2 (see X-ray structure of 2h in Figure 1). Allenes 1a,b were specially isolated to compare their reactivity with

• high positive charge on it. Another pathway may be an electrophilic cyclization at the ortho-carbon in the S-phenyl ring. Then, the preparative reactions of allene 2a under the action of different electrophilic reagents were conducted. Transformations of 2a using an excess of various Brønsted acids

• reaction solution with a low nucleophilic medium (frozen aqueous HCl at −60 °C) gave almost quantitatively butadiene Z-3a with a small admixture of its E-isomer (Table 3, entry 4). Weaker acids, CF3CO2H or aqueous HCl, did not activate allene 2a, no reactions took place (Table 3, entries 5 and 6). Apart

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• reaction of a (trimethylsilyl)allene and a suitable cyclic α,β-unsaturated ketone [30][31]. Despite the applicability of the reaction to construct five-membered rings, it has not been extensively examined [32] for the synthesis of complex natural products. As depicted in Scheme 2, the hydrindane core ring

• . Gratifyingly, treatment of 4 with TiCl4 in the presence of commercially available 1-methyl-1-(trimethylsilyl)allene at −78 °C for 1 h afforded the desired cis-6,5-bicylic core 5 in 63% yield as a single diastereomer. The desilylated product 6 was also obtained as a mixture of diastereomers. The high

• stereoselectivity of the ring-formation step can be explained by the suprafacial addition of the allene to the double bond of the α,β-unsaturated compound 4, the diastereoselectivity being sterically controlled by the methyl group on the β-face. The transformation of the vinylsilane moiety in 5 into the

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• carbinols afforded novel allene systems. Our study may be of help towards the total synthesis of solenopodin or klysimplexin derivatives. Keywords: conformational analysis; low valent titanium; marine natural products; pinacol coupling; ten-membered rings; Introduction Eunicellane-type diterpenoids share

• )-isomer of 24, compound 31, via Sonogashira coupling with the (E)-isomer [11] of 12. Chlorinated allene 32 was formed from 31 as the only product on treatment with SOCl2/pyridine, presumably after chlorosulfonation, followed by chlorine transfer and loss of SO2 (Scheme 5). There is precedence that

• elimination towards the cyclohexene can be a competing process [26]. The configuration of the allene moieties could not be elucidated. Interestingly, treatment of 31 with Tf2O/pyridine afforded allenyl triflone 34, with 13C NMR signals of the allene center and the triflyl-substituted carbon at δ 203.7 and

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• succinimides 50 in good yields (Scheme 31a) [87]. Likewise, oximes 51 [88] were also efficient participated in the hydroarylation of maleimides (Scheme 31b). 3. Hydroarylation of allenes An allene is an exceptional functional group in organic synthesis due to its cumulative double bonds [89][90]. In this

• , a plausible mechanism was proposed. The reaction starts with the generation of the active cobalt(III) species G1 from [Cp*CoI2(CO)], AgSbF6, and arene 53. Subsequently, C–H metallation of G1 by ligand-to-ligand hydrogen transfer provides cobaltacycle G2 and an allene insertion gives intermediate G3

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• the coupling (Table 1, entries 3–5). Thus, the removal of CrCl3 resulted in the formation of a trace amount of 4a with the complete consumption of allene 2a, whereas most of iodoarene 1a and aldehyde 3a remained unreacted after the reaction was completed (Table 1, entry 3). Using a Zn reductant

• reaction conditions mainly afforded the anti-configured homoallylic alcohols 7–10 in 46–65% yield. A similar reversed diastereoselectivity was observed in the coupling reaction of silyloxy allene 6, leading to 11 in 46% yield (anti/syn = 73:27). A stoichiometric reaction using phenylchromium(II or III

• ) reagents, generated from the reaction of CrCl2 or CrCl3(thf)2 with phenyllithium [19][20], in the presence of allene 2a and aldehyde 3c provided diarylmethanes in 78–85% yields without the visible consumption of allene 2a (Scheme 10, reaction 1). Furthermore, in the absence of the CrCl3 catalyst, allene 2a

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• -triene (78), and triplet 2-naphthylcarbene (79). Formation of allene 83 as an alternative carbene rearrangement product was not detected under the studied photolysis conditions (Scheme 14). Kitahara’s group reported the one-step synthesis of heptafulvalenes and benzoheptafulvalenes from monocyclic

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• . Experimental evidence suggests that a radical mechanism is involved. Keywords: allene; chlorination; hypervalent iodine; synthetic methods; vinyl chloride; Introduction Organochlorine compounds are vital as polymer precursors [1], as pharmaceuticals [2][3] and agrochemicals [4][5][6] and as functional

• (4). Results and Discussion We began our investigation of allene chlorination using p-tolylallene (2a), prepared from 4-methylstyrene through Doering–Moore–Skattebøl reaction [46], and iodane 1a. The reaction was carried out using a slight excess of 1a in acetonitrile, at both room temperature and at

• reflux, and upon consumption of the allene an inseparable mixture of chlorination products 3a and 3a’ were obtained. While the overall yield of the chlorinated products increased when under reflux conditions, very little change in chemoselectivity was observed (Scheme 2) [31]. As these results were

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• deprotonation of a benzyl proton in intermediate C giving the allenic product D. At high temperature, deprotonation of allene D prefers to form anion E in the presence of KF, which is converted to anion F through a resonance effect. Protonation of intermediate F would then furnish the propargyl

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• fluoride leads to deprotonation in the Cα-position of 6i, 6k and 6j, inducing an alkyne rearrangement to form an allene, which rearranges further to provide an α,β-unsaturated imine (Figure 8) [97]. One target application of propargylamines 7 is the Sonogashira cross-coupling with halogenated benzoates

• turned brightly yellow when treated with bases like piperidine. The X-ray crystal structures of 11i and 12i confirm unequivocally the structure of the products and thus the postulated two-step rearrangement. Both, the rearrangement of the alkyne to the allene and the subsequent tautomerism to the α,β

• approach. Electron-withdrawing substituents in the Cα-position induced an irreversible alkyne–allene-α,β-unsaturated imine rearrangement under mild basic conditions, which makes an alkaline racemization of propargylamines improbable. Altogether, a large set of propargylamines with various amino acid

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• ][14][15]. For example, the preparation of C3-borylated benzothiophene by BCl3-induced borylative cyclization of arylalkynes was recently demonstrated by Ingleson [16]. Allene-mediated cyclization reactions are advantageous due to the convenient preparation of starting materials instead of the use of

• unstable or reactive polyfunctionalized allene substrates [17][18][19][20][21][22][23][24][25][26][27]. Although transition metal (e.g., Au, Pd)-catalysed propargyl–allenyl isomerization and cyclization reactions have been established [28][29], such transformations promoted by a base to construct

• -pot process. Based on our understanding of organosulfur chemistry [20][21][22], we report herein a simple, metal-free method for the formation of benzothiophenes using an intramolecular addition of a sulfur atom (originated from a sulfide) to the electron-deficient allene moiety generated in situ by a

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• formed propargyl group is isomerized to an allene moiety, obviously due to the excess of the strongly basic lithium salt [35]. This unexpected monosubstitution remains unexplained and is not applicable as basis for a general selective synthesis of monoalkynylcamphor derivatives. Alkynes can also be

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• formation of 12d. Since the central carbon atom of an allene unit is more electropositive, the carbon atom can undergo an attack by the amide nitrogen atom to form a six-membered ring. In the case of 7a–c, the formation of allenic intermediates is out of question [15]. Based on our experimental results, we

• and methylene protons in 13c and 16 with the relevant carbon atoms (from the HMBC spectrum). Single-crystal X-ray structure of 12c shown with 40% probability displacement ellipsoids. The structure of allene 17 formed during the reaction of 7d with a base. Single-crystal X-ray structure of 19c shown

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• colleagues showed that similar reactions can be extended to compounds with triple bonds and allene fragments [14]. Recently we have shown that the catalytic decomposition of diazomalonates and other diazoesters using Rh(II)- and Cu(II)-complexes in the presence of α,β-unsaturated δ-(N-aryl)amino esters 1

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• imines, carbonyls or allene homologs. The resulting homologated nucleophile 8 may then be trapped in an intramolecular fashion by a π-allyl complex, which may concomitantly form from 6 through activation of the homoallylic functionality with a suitable transition metal catalyst. According to this concept

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• corresponding products were found to have improved diastereoselectivities. Phenols with electron-withdrawing groups failed to afford the expected products under the same conditions. Mechanistically, Ga(OTf)3 may activate the allene and phenol substrates simultaneously via the bidentate model. In contrast, the

• spirocyclic 2,5-dihydrofuran was obtained in 98% yield when the π acid AuCl3 (5 mol %) was used. AuCl3 may coordinate one of the allene double bonds via a monodentate model. The phenol substrate did not participate in this reaction. In 2013, Ji and co-workers described the I2-catalyzed construction of pyrrolo

Solving the puzzling competition of the thermal C²–C⁶ vs Myers–Saito cyclization of enyne-carbodiimides

• Anup Rana,
• Mehmet Emin Cinar,
• Debabrata Samanta and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 43–49, doi:10.3762/bjoc.12.6

• approach for the diradical species and the transition states (TSs) connecting them while the restricted method was used for closed shell species. The BLYP functional was chosen for computation because the benchmark studies done by Schreiner showed good applicability of BLYP for the enyne-allene system [3

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• /allene cycloaddition, discovered by Himbert and Henn were found to undergo a RRM in a facile manner in the presence of catalyst 6 to produce complex polycyclic lactams. In this regard, the required building block 319 was obtained from compound 318 by cycloaddition reaction. A variety of complex molecular

Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH₄SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition

• A. Srinivas Reddy and
• Kenneth K. Laali

Beilstein J. Org. Chem. 2015, 11, 1641–1648, doi:10.3762/bjoc.11.180

• additions in halofunctionalization with TMSX/Selectfluor and thiocyanation reactions with NH4SCN/Selectfluor. These competing pathways are influenced by the nature of the anion, allene structure, and the choice of solvent. Keywords: allene esters; oxidative electrophilic dihalogenation/conjugate addition

• order to examine a possible influence of the structure of the allenoate on the product distribution, allene esters 2–6 were synthesized (Figure 1). The reactions of ethyl allenoate (2) with TMSBr, TMSI and with NH4SCN were studied in the presence of Selectfluor in MeCN and DMF (Scheme 5). With TMSBr and

• , especially in reactions with TMSI/Selectfluor (see Scheme 10), appears consistent with stabilization of the incipient allenyl cation in the oxidative/electrophilic pathway. Allene esters synthesized for this study. Reaction of benzyl allenoate (1) with TMSBr with and without Selectfluor (E/Z designations, as

Why base-catalyzed isomerization of N-propargyl amides yields mostly allenamides rather than ynamides

• Armando Navarro-Vázquez

Beilstein J. Org. Chem. 2015, 11, 1441–1446, doi:10.3762/bjoc.11.156

• propargyl bromide (Scheme 1) [6][7]. Subsequent base-catalyzed isomerization of N-propargyl compound 2 leads to allenamide 3. Whereas in some particular cases the reaction leads to the final N-alkynyl product, in most cases, the reaction stops at the allene stage and does not further progress even when

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• may possess further functionalities in addition to the phosphorus center such as the γ-hydroxypropyl group which results from the ring opening and π-donor moieties such as aryl, allyl, propargyl and allene which originates from the Grignard reagent. Keywords: chirogenic phosphorus; Grignard reagents

• . Further heating did not provide higher conversion. Following hydrolytic work-up and flash chromatographic purification the product was identified as allene 5f, rather than acetylene 5h, due to propargyl–allene rearrangement (Scheme 5). Most characteristic are the 13C NMR chemical shift of HC=C=CR at

• formed regioselectivly. Synthesis of acetylene and allene phosphine oxides. Synthesis of γ-hydroxypropyl (±)-phosphinatesa and related compounds. Synthesis of γ-hydroxypropyl (±)-phosphine oxidesa. Supporting Information Supporting Information File 66: Experimental details, characterization data and 1H

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

• reacted with azetidine-2,3-diones 176 under eco-friendly reaction conditions to generate bis(allene) 177. Compound 177 was then converted into bis(dihydrofuran) 178 by using AuCl3. Macrocyclization of 178 was carried out by using a Ru(II) or Ru(III) catalyst to generate 179 as a mixture of E/Z isomers

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• be envisioned that this compound results from the rearrangement of an allene oxide (Scheme 5). Interestingly the dipropargylic alcohol 9 afforded the rearranged allylic ether 20 as the only isolated product (entry 6, Table 1). In order to improve the yields of these reactions and gain insight in the

Chiroptical properties of 1,3-diphenylallene-anchored tetrathiafulvalene and its polymer synthesis

• Masashi Hasegawa,
• Junta Endo,
• Seiya Iwata,
• Toshiaki Shimasaki and
• Yasuhiro Mazaki

Beilstein J. Org. Chem. 2015, 11, 972–979, doi:10.3762/bjoc.11.109

• , Chiba 275-0016, Japan 10.3762/bjoc.11.109 Abstract A novel tetrathiafulvalene dimer, bridged by a chiral 1,3-diphenylallene framework, has been prepared as an optically active compound having strong chiroptical properties. Although a chiral allene bearing strong electron-donating group(s) often

• undergoes slow photoracemization even in daylight, the present allene is totally configurationally stable under ordinary conditions. Each isomer possesses pronounced chiroptical properties in its ECD spectra reflecting the chiral allene framework. Moreover, the elongation of the chiral main chain was also

• carried out by direct C–H activation of the TTF unit, and the chiroptical properties of the resulting polymer were also investigated. Keywords: allene; axial chirality; chiroptical properties; redox; tetrathiafulvalene; Introduction Recently, there has been a growing interest in chiral π-conjugated

Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• , stepwise synthesis of a family of acene derivatives from various acyclic precursors is normally very step intensive. The prevalence of these issues in the synthesis of substituted tetracenes caused Lin [14], building on the anthracycline natural product work of Saá [15], to introduce a 1,2-bis-allene

• and the mixture allowed to come to ambient temperature. This resulted in the smooth formation of allene 14. In particular, the presence of allenic and C=O signals in the 13C NMR spectrum at 212.1 and 188.5 ppm and the absence of any alkyne C≡C resonances in the region δC 80–90 are indicative of this

• rapid access to mono sulfur-containing acenes, and is applicable to small scale library synthesis. Only low cost reagents are required and otherwise difficult to synthesise hindered 1,3,4,12-tetrasubstituted species can be made straightforwardly. Use of bis-allene intermediates 2 for rapid access to