2-(1-Hydroxypropyn-2-yl)-1-vinylpyrroles: the first successful Favorsky ethynylation of pyrrolecarbaldehydes

• A. V. Ivanov,
• V. S. Shcherbakova,
• I. A. Ushakov,
• L. N. Sobenina,
• O. V. Petrova,
• A. I. Mikhaleva and
• B. A. Trofimov

Beilstein J. Org. Chem. 2015, 11, 228–232, doi:10.3762/bjoc.11.25

• acetylene–allene isomerization of the secondary acetylenic alcohols 2a–j formed. The reaction is carried out at atmospheric pressure (acetylene flow, 7–10 °C, 2–4 h). The yields of hydroxypropynylpyrroles 2a–j range from 53–94% (Table 1). The reaction was monitored by GLC and was stopped after complete

• of isolated yields is attributable not only to the difference in the reactivity of aldehydes 1a–j, but also to the propensity of the product to undergo acetylene–allene isomerization to give the polymerizable vinyl ketones [21]. As seen from Table 1, the reaction tolerates a wide scope of pyrrole-2

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• electron-deficient imines with allenes. On the other hand, the rigid bridged [2.2.1] bicyclic chiral phosphine A3 appears to be an excellent catalyst for allene/imine [3 + 2] annulation. With a chiral phosphine-catalyzed [3 + 2] annulation of an indole-derived imine and an γ-ethylallenoate as the key step

• , Lu and co-workers explored imine–allene [3 + 2] annulations catalyzed by a dipeptide-derived phosphine [68]. They identified the phosphine H12, a close analogue of H10, as the most suitable catalyst. In the presence of 5 mol % of H12, a wide range of alkylimines and various arylimines could be

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• should be routed through α-linolenic acid-derived allene oxide (Scheme 3) [16]. The addition of H2O to this intermediate gives α,β-unsaturated-γ-ketol, which accepts further oxidation at the α'-position, and macrolactonization of the resulting α',γ-ketodiol would yield 1. Similar, but rather simpler

• metabolites were found from corn [17][18]. However, they comprise a pair of enantiomers and thus should be generated non-enzymatically from α-linoleic acid-derived allene oxide. In contrast, 1 is optically active and is more likely to be produced by a sequence of enzymatic reactions. Sacrolide A (1) inhibited

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• -allene. The Lewis acid-induced rearrangement of this heterocycle provided the corresponding bicyclic 1,2-oxazine derivative that may be regarded as internally protected amino sugar analogue. After subsequent reduction of the carbonyl group, the resulting bicyclic compound was used for Suzuki cross

• ]-cyclization of D-isoascorbic acid-derived (Z)-nitrone 6 and lithiated TMSE-allene 5. Results and Discussion For our synthesis of new divalent carbohydrate mimetics we required 1,2-oxazine derivatives derived from (Z)-nitrone 6 and lithiated alkoxyallenes. The 4-bromophenyl group should allow transition metal

• observed. Due to the complexation of lithiated allene 9 to the nitrone 6 an exclusive formation of the two syn-1,2-oxazines 4 was observed. This result suggests that the configuration at C-2 of the dioxolane moiety has no influence on the stereochemical outcome of the reaction. The model suggested by

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• nucleosides 93 were also prepared by this method. 7. The carbopalladation of dienes A reaction of an aryl halide, an unsaturated alkene (diene, allene), and an amine catalyzed by Pd(0) species, referred to as carbopalladation of dienes, results in the three-component assembly of an unsaturated amine (Scheme

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• methodology, we explored the addition of hydroxypyrones to both an allene and an internal alkyne to furnish a trisubstituted enol ether. Addition of 4-hydroxy-6-methyl-2-pyrone (3a) to the terminal allene 8 under the optimised conditions proceeded smoothly to give the trans-trisubstituted enol ether 9 in 52

• desired product. The phacelocarpus 2-pyrones 1 and 2. Generalised O-functionalisation of 6-alkyl-4-hydroxy-2-pyrones 3. Synthesis of alkylated 2-pyrones 3b–e. Michael addition of 3a to allene 8 and internal alkyne 10. Synthesis of 2-pyronyl ethers 4a–l. Michael addition reaction optimisation. Synthesis of

Allenylphosphine oxides as simple scaffolds for phosphinoylindoles and phosphinoylisocoumarins

• G. Gangadhararao,
• Ramesh Kotikalapudi,
• M. Nagarjuna Reddy and
• K. C. Kumara Swamy

Beilstein J. Org. Chem. 2014, 10, 996–1005, doi:10.3762/bjoc.10.99

• the interemdiate allene [29]. Many other unusual transformations have also been reported recently [31]. In another reaction leading to phosphinoylindenone depicted in Scheme 1c, an intramolecular ene-reaction is possibly involved and in Scheme 1d the reaction led to phosphinoylisochromenes via

• deprotection of an allene intermediate under Lewis acid mediation [22]. In this context it was of interest to see, in a reaction like that shown in Scheme 1c, whether the introduction of an amide or a carboxylate ester in place of the –CHO group could lead to phosphinoyl-subtstituted indoles/isocoumarins via

• formed (Scheme 3). The presence of a doublet for PCH carbon at δ 48.3 with a 1J(P–C) value of 62.0 Hz reveals that the phosphorus moiety is attached to an sp3-hybridized carbon. On the other hand, in the reaction using the =CHMe allene 3m, two isomers in which the N–H proton moves to either the α-carbon

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• dealing with the use of BINAP–AgClO4 as a chiral catalyst in the same two-component reaction [98]. Higher enantioselectivities were rarely observed with SbF6− being the weaker coordinating counter ion. An interesting application of silver catalysis in the allene chemistry field has been recently proposed

• [2 + 2 + 1] cycloaddition of allenoates 84, dual activated olefins 85, and isocyanides 83 (Scheme 39). It is noteworthy, that only the external double bond of the allenic fragment is embedded in the final carbocyclic ring, whereas in the phosphine-catalyzed [3 + 2] cycloadditon process the allene

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• – discovered and mechanistically elucidated by Oliver Flögel – features a three-component reaction that employs alkoxyallenes, nitriles and carboxylic acids: upon treatment with n-butyllithium the allene is lithiated in α-position to the alkoxy moiety; the addition of a nitrile as electrophile to this highly

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• enantiopure nitrones and lithiated TMSE-allene we prepared three 1,2-oxazine derivatives which underwent a highly stereoselective Lewis acid-induced rearrangement to give bicyclic products in good yield. Subsequent reductive transformations delivered a library of new poly(hydroxy)aminooxepane derivatives. The

• ]. The general approach is shown in Scheme 1: the chiral pool-derived nitrones A [29][30] undergo a [3 + 3]-cyclization with lithiated [2-(trimethylsilyl)ethoxy]allene (TMSE-allene) [31] as C-3 building block [32] to form the 3,6-dihydro-2H-1,2-oxazines B; subsequent Lewis acid-promoted reactions [23

• a Dondoni protocol [29]. This route allows the synthesis of enantiopure nitrone 3 in multi-gram scale. The enantiopure (Z)-configured nitrones 6, 8 and 3 were treated with in situ lithiated TMSE-allene at −78 °C furnishing the expected 1,2-oxazines syn-7 [37], syn-9 and syn-10 in high yields and

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• adduct in a good yield. We then turned to the lithiated nucleophile 31. In THF at −78 °C high diastereoselectivity (15:1 anti/syn) was obtained. Unfortunately, direct reduction of 32 to 59 produced allene as a byproduct, which forced us to modify the synthetic route. We have also successfully used (Z

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• toward a number of complexity-oriented transformations. In this segment, gold-catalyzed addition of carbon- and heteroatom-based nucleophiles to inactivated alkenes are widely recognized as “capricious” transformations due to alkyne and allene counterparts [1][2][3][4][5]. However, over the past few

• with enantiopure substrates. The proposed mechanism proceeded through 3,3-migration of the propargylic ester to form the allenoate 87. The expected activation of the allene was probably unfavoured for steric reasons, therefore gold activation of the alkene moiety triggered attack of the more

• nucleophilic double bound of the allene, forming the intermediate 88. Finally, condensation of the alkylgold 88 onto the carbonyl group led to the bicyclic product 84 (Scheme 23). An interesting example of gold-catalyzed intramolecular cyclopropanation of olefins was recently documented by Maulide and

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• block and allowed the synthesis of both enantiomers of the natural product in a fairly short manner (seven steps starting from the allene). The 5-endo-cyclization of allenyl alcohols 12 and 13 by gold catalysis afforded a separable mixture of diastereomeric dihydrofurans 14 and 15 in good yield

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• ether; Introduction The past decade has witnessed the fast growth of homogeneous gold catalysis as one of the important branches in transition-metal chemistry [1][2][3][4][5][6][7][8][9]. The utility of cationic gold(I) complexes as π-carbophilic acids toward alkyne and allene activation renders them

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• processes. Keywords: alkyne; allene; asymmetric catalysis; cycloaddition; enantioselective; gold; gold catalysis; Introduction In the past decade, there have been extraordinary advances in the development of novel stereoselective gold(I)-catalyzed transformations [1][2][3][4][5][6][7][8][9][10]. In this

• , we will present cycloaddition processes (i) with a gold–carbene intermediate, (ii) involving an allene activation to generate a gold–allyl cationic intermediate and, (iii) in which the proposed key reactant is a vinylgold zwitterionic species. Review Cycloadditions involving gold–carbene

• enantioselectivity. Cycloadditions initiated by activation of allenes Gold(I) catalysts can efficiently activate allenes in a highly chemoselective way, triggering the formation of allenyl cationic species. Different structures have been proposed to represent these gold-activated allene complexes, including η2

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• allene synthesis by copper-mediated SN2’-substitution [51] (Table 1, see below). In order to establish suitable reaction conditions, we first examined the synthesis of the butyl-substituted model substrate 6a. Treatment of propargyl tosylate 5a with the organocopper reagent formed in situ from n-BuMgCl

• , CuBr·SMe2, and LiBr [52] afforded allene 6a with up to 74% yield (Table 1, entries 1–3). In order to achieve complete conversion, a large excess of the nucleophile is required. The yield could be raised further by using the cyanocuprate n-BuCu(CN)MgBr [53][54][55] or the heterocuprate n-BuCu(SPh)Li [56

• 5b as starting material, allene 6a was obtained in 85% yield using n-BuCu(CN)MgBr·2LiCl as nucleophile (Table 1, entry 6). In contrast, use of the heterocuprate n-BuCu(SPh)Li led to decomposition (Table 1, entry 7). Propargyl phosphate 5c is also a suitable precursor of allene 6a (Table 1, entries 8

Gold-catalyzed cyclization of allenyl acetal derivatives

• Dhananjayan Vasu,
• Samir Kundlik Pawar and
• Rai-Shung Liu

Beilstein J. Org. Chem. 2013, 9, 1751–1756, doi:10.3762/bjoc.9.202

• product 4e in 52% yield according to initial E-configured 1e. The structure of compound 4e was determined by 1H NMR NOE spectra. The reaction was still operable with 1f, bearing a 1,2-disubsituted allene, giving the desired 4f in moderate yield (49%). Its E-configuration was determined by NOE measurements

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• phosphine oxides OC-64 and OC-69 for the enantioselective desymmetrization of meso-stilbene oxide to provide the corresponding vicinal chlorohydrin 96 in up to 82% ee. More recently, Ready [86] and co-workers have synthesized a series of chiral phosphine oxides (OC-70 to OC-77) based on an allene backbone

• oxides. The variation of the substituents on the allene itself was tolerated in the desymmetrization processes, but both the yields and the enantioselectivities are sensitive to changes in the aryl rings on the phosphine oxide. It was found that the diphenyl-substituted catalyst OC-73 is a highly

• meso-epoxides. Some chiral phosphoramide and chiral phosphine oxides. The proposed mechanism of the chiral HMPA-catalyzed desymmetrization of meso-epoxides. The Chiral phosphine oxides (OC-70 to OC-77) based on an allene backbone. Chiral pyridine N-oxides used in enantioselective desymmetrization of

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• thiophosphination (Scheme 9). Detailed mechanistic studies revealed that comproportionation between PhSe–SePh and Ph2P–PPh2 occurs smoothly to generate PhSe–PPh2 as the actual reactive species. Selenophosphination of terminal allene affords (2-phenylselenyl-2-alkenyl)diphenylphosphine regioselectively (Scheme 11

Gold-catalyzed intermolecular hydroamination of allenes with sulfonamides

• Chen Zhang,
• Shao-Qiao Zhang,
• Hua-Jun Cai and
• Dong-Mei Cui

Beilstein J. Org. Chem. 2013, 9, 1045–1050, doi:10.3762/bjoc.9.117

• the intermolecular hydroamination of allenes with sulfonamides is shown. The reaction proceeded smoothly under mild conditions for differently substituted allenes giving N-allylic sulfonamides in good yields with high regioselectivity and E-selectivity. Keywords: allene; gold catalysis

• -donating or an electron-withdrawing group gave good isolated yields of the corresponding adducts (Table 3, entries 1 and 2). Whereas hydroamination of the monosubstituted heteroaromatic allene 1d also lead to the conversion into the expected addition product 3j, hydroamination of the monoalkyl-substituted

• aliphatic allene 1e formed a 71:29 mixture of linear product (3ka) and branch product (3kb) under the same conditions (Table 3, entry 4). Furthermore, disubstituted allenes also worked well. Differentially 1,1-disubstituted allene 1f reacted with sulfonamide to afford trans-adducts 3l with high selectivity

Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

• Benito Alcaide,
• Pedro Almendros,
• M. Teresa Quirós and
• Israel Fernández

Beilstein J. Org. Chem. 2013, 9, 818–826, doi:10.3762/bjoc.9.93

• ][37][38][39][40][41]. The Boc protective group has been widely used in allene chemistry, being an inert and recommended partner in gold- and palladium-catalyzed aminocyclizations of allenes [42]. On the other hand, reports of gold-catalyzed cyclizations leading to heterocycles that contain more than

• one heteroatom are rare [43][44][45][46][47][48]. Besides, it has been reported very recently that the Au(I)-catalyzed cyclization of a N-phenethyl-N-Boc-protected allenamide failed [49]. Despite the above precedents, but in continuation of our interest in heterocyclic and allene chemistry [50][51][52

• 3,4-dihydro-2H-1,3-oxazin-2-ones 4 (arising from 6-exo-dig cyclization) were achieved, with the nucleophilic oxygen attacking the central allene carbon atom in each case. This is an interesting result, because the available examples on related metal-catalyzed allene heterocyclizations usually lead 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

• –Fuchs reaction followed by quenching of the acetylide with cyclohexanone furnishes propargyl silane 136, a compound that is cleanly transformed into allene 137 upon exposure to tetrabutylammonium fluoride [54]. This approach represents perhaps the most versatile route to functional propargyl silanes

• . Synthesis of bicyclic cyclobutane motifs. Construction of the CD rings of steroids. Rapid assembly of polyquinanes. Formation of a polycyclic structure via an allene intermediate. A polycyclic structure via the alkylative Birch reduction. Synthesis of polycyclic pyrimidines and indoline structures

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• with 5J = 2.8 Hz for the remaining allenic proton in the 1H NMR spectrum and by two singlets at δ 202.5 and 202.8 ppm for the central allene carbon atoms in the 13C NMR spectrum. When the methylation is carried out after 3 equiv of n-butyllithium have been added, small amounts of a dimethyl product

• propargyl structure. The “half-rearranged” diol 24 is a slightly yellow oil at room temperature. Structure-defining are the missing allene proton and three signals for carbon atoms not connected to a hydrogen atom: the central allene carbon atom at 210.0 ppm and the two acetylene carbon atoms at δ 72.0 and

• metalated allenes has often been described in the chemical literature [17]. And the process is apparently successful for 2/4 also: the 1H NMR spectrum of the raw product, obtained in ca. 70% yield, shows the expected signals at δ 5.59 ppm (5J = 2.9 Hz) for the remaining allene proton and at 9.5 ppm (broad

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• organic synthesis for the first time. All classes of compounds containing at least two allene moieties are considered, starting from simple conjugated bisallenes and ending with allenes in which the two cumulenic units are connected by complex polycyclic ring systems, heteroatoms and/or heteroatom

• bisallene with unsubstituted allene carbon atoms [9]. And finally, also in the 1960s, Jacobs and Prempree reported on the synthesis of the first hexa-alkylated bisallene, hydrocarbon 5 [10][11]. We shall return to the preparation of these three compounds later. The upsurge in interest in allene chemistry is

• a recent phenomenon. During the 1970s (the very few) German chemists working on and with allenes used to answer inquiries about their research interests with the (German) sentence, “Ich arbeite (ueber) Allene”, with allene being Berlin dialect for “alone”, i.e., “I am working alone/on allenes”. The

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• ) catalyst to the indole nitrogen giving the Pd(II)-hydride complex XIV. Such an intermediate would be susceptible to insertion of the allene group into the Pd–H bond to generate the π-allyl-Pd(II) complex XV, which in turn would undergo the intramolecular formation of the new carbon–nitrogen bond, which