Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• as particularly efficient for maximizing structural diversity [3]. Previous work in the Brummond laboratory has demonstrated that an allene-containing β-carboline provided a good starting point for synthesizing six novel types of hetero-frameworks, all skeletally unique [4]. Moreover, scope and

• the mixtures could not be readily separated by column chromatography, diastereomeric ratios were determined by 1H NMR and were advanced without further purification. Reaction of allene 6 under the silver-nitrate-mediated cyclization conditions afforded the desired fused pyrrolines 1. However, in the

• -phosponium hexafluorophosphate (PyBroP), provided the requisite allene-yne substrates 9{1,2}–9{1,8}. For the coupling reaction of the ynoic acids with an aryl group on the terminus of the alkyne 8{5–8}, the desired allene-ynes 9{1,5}–9{1,8} were afforded along with the [2 + 2] cycloadducts 2{1,5}–2{1,8

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• chiral NHC–Au(I) complexes (4–6) with a binaphthyl or biphenyl framework [13][14]. These Au(I) complexes were applied to catalyze the asymmetric cyclization of 1,6-enynes or allene in up to 70% ee, and the asymmetric intramolecular hydroamination of allene in up to 44% ee. We previously reported a novel

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• quenched with water. Then, warming to room temperature was followed by extraction with Et2O (3 × 25 mL), and the combined organic layers were stirred overnight with the drying agent (MgSO4). When cyclisation of the primarily formed allene adducts was complete (TLC monitoring, hexane/ethyl acetate 4:1, p

Synthesis of fluoranthenes by hydroarylation of alkynes catalyzed by gold(I) or gallium trichloride

• Sergio Pascual,
• Christophe Bour,
• Paula de Mendoza and
• Antonio M. Echavarren

Beilstein J. Org. Chem. 2011, 7, 1520–1525, doi:10.3762/bjoc.7.178

• (Table 2, entries 11 and 12). The reaction of 3a with Pd(OAc)2 as catalyst proceeded differently to give known (E)-9-(3-phenylallylidene)-9H-fluorene (9) [60], presumably via the formation of the corresponding allene as an intermediate (Scheme 2). Substrates 7b–j, prepared by alkylation of fluorenyl

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• partners through a Pd-mediated allylic amination The allene carbopalladation process with organic halides is known to generate a π-allylpalladium intermediate, which can be trapped by intermolecular carbo- or heteronucleophiles to produce the corresponding three-component adduct. This strategy was used by

• Ma and coworkers for the selective preparation of five-membered nitrogen heterocycles starting from allene-bearing nucleophilic centers [41]. In this context, the same authors developed a new synthesis of substituted imidazolidinones 75 through a palladium-catalyzed, three-component reaction of 2,3

• -allenylamines, organic halides and isocyanates [42]. In this process, there is first a carbopalladation of the functionalized allene with the aryl iodide, followed by reaction of the internal aza-nucleophile with the highly electrophilic isocyanate derivative, before premature trapping of the initially formed π

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• . In this review we will summarize some of the most remarkable examples, and present the mechanistic rational underlying the transformations. Keywords: alkene; alkyne; allene; catalysis; cycloaddition; gold; Introduction In modern organic synthesis, the criteria of efficiency, versatility, economy

• cases, the gold activation of the alkyne promotes a 1,3-acyloxy shift that leads to ketone allenic intermediates of type VI (Scheme 3) [42][43]. Then, an intramolecular attack of the carbonyl group on the activated allene generates a benzopyrilium intermediate (VII) which undergoes a concerted and

• related cycloaddition reactions. Indeed, the group of Toste described in 2007 a (2 + 2) intramolecular cycloaddition reaction between allenes and alkenes by gold catalysis [87]. The proposed mechanism is based on an activation of the allene to give a cationic metal species which undergoes a cyclization to

Triazole–Au(I) complex as chemoselective catalyst in promoting propargyl ester rearrangements

• Dawei Wang,
• Yanwei Zhang,
• Rong Cai and
• Xiaodong Shi

Beilstein J. Org. Chem. 2011, 7, 1014–1020, doi:10.3762/bjoc.7.115

• , which allowed the effective activation of the alkyne without affecting the reactivity of the allene ester intermediates. These results led to the investigation of the preparation of allene ester intermediates with TA–Au catalysts under anhydrous conditions. As expected, the desired 3,3-rearrangement

• . Keywords: allene; chemoselectivity; gold catalysis; ligand effect; organometallic; Introduction The past decade has seen rapid growth in the use of homogeneous gold catalysis for conducting powerful organic transformations [1][2][3][4][5][6][7][8][9]. Like many other transition metal complexes, the

• one of the most important reaction modes in the Au(I) promoted transformation [21][22][23][24][25][26][27][28][29][30][31]. Recent experimental and computational mechanistic studies revealed the 3,3-rearrangement to form the allene ester intermediate [32][33] as the key step in this transformation

Toward an integrated route to the vernonia allenes and related sesquiterpenoids

• Da Xu,
• Michael A. Drahl and
• Lawrence J. Williams

Beilstein J. Org. Chem. 2011, 7, 937–943, doi:10.3762/bjoc.7.104

• Da Xu Michael A. Drahl Lawrence J. Williams Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854, USA 10.3762/bjoc.7.104 Abstract The synthesis of a model endocyclic allene related to the vernonia allenes is described

• present sequence are also discussed. Keywords: C–C fragmentation; endocyclic allene; natural product; total synthesis; Introduction Well over 150 allene-containing natural products are known [1][2][3][4][5]. Among these, intriguing complex structures were assigned by Bohlmann and co-workers to isolates

• from the aerial parts of Vernonia species collected mainly from northern Brazil about 30 years ago (1–3, Figure 1) [6][7][8]. These bicyclic germacranolides are the only known endocyclic allene-containing natural products. Interestingly, no synthetic studies of these complex natural products have been

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• rearrangement followed by nucleophilic attack of the Boc-protected nitrogen atom. A similar method to synthesize the 2-vinylpiperidin-3-ol 158 by a highly stereoselective gold-catalyzed allene cyclization has been reported (Scheme 27) [72]. The ring expansion of cyclopropane derivatives provides a powerful

• catalytic amount of phosphite–gold(I) pre-catalyst and a silver additive. Notably, the addition is regioselective for the allene terminus, and generates (E)-allylation products 202. The direct C–H functionalization of indoles or pyrroles is an efficient method for the introduction of vinyl and aryl groups

• 222, while the stereochemistry of the reaction depends on the ring size. In some gold(I)-catalyzed cycloaddition reactions, regiochemistry of the product is controlled by the ligand [100][101]. For example, the triphenylphosphinegold(I)-catalyzed reaction of allene–diene 224 provided a 2:1 mixture of

Gold(I)-catalyzed formation of furans by a Claisen-type rearrangement of ynenyl allyl ethers

• Florin M. Istrate and
• Fabien Gagosz

Beilstein J. Org. Chem. 2011, 7, 878–885, doi:10.3762/bjoc.7.100

• new strategies that involve a metal-mediated cyclization of an allene or an alkyne derivative with an oxygen functionality have appeared in the literature [7]. Among the transition metals that are commonly employed in these transformations (viz. Cu, Ag, Pd and Au), gold has proven to be particularly

Gold-catalyzed oxidation of arylallenes: Synthesis of quinoxalines and benzimidazoles

• Dong-Mei Cui,
• Dan-Wen Zhuang,
• Ying Chen and
• Chen Zhang

Beilstein J. Org. Chem. 2011, 7, 860–865, doi:10.3762/bjoc.7.98

• to form α-diketones and aldehydes in good yields is presented. Further directed synthesis of quinoxalines and benzimidazoles, via the condensation of the resulting α-diketones and aldehydes with benzene-1,2-diamine, was achieved in high yields. Keywords: allene; benzimidazole; gold-catalysis

• -withdrawing fluoro or bromo substituent on the benzene ring also took place smoothly (Table 2, entries 5 and 6). Disubstituted allenes were also examined. Thus, the 1,3-disubstituted allene 1g, was oxidized to afford α-diketone 2g and aldehyde 3c in 35% and 32% yields, respectively (Table 2, entry 7

• of quinoxalines and benzimidazoles via the condensation of the resulting α-diketones and aldehydes with benzene-1,2-diamine was achieved in high yields. This reaction appears to proceed via oxidation/hydration and oxidative cleavage of the allene, and investigations into the mechanism of this

Homoallylic amines by reductive inter- and intramolecular coupling of allenes and nitriles

• Peter Wipf and
• Marija D. Manojlovic

Beilstein J. Org. Chem. 2011, 7, 824–830, doi:10.3762/bjoc.7.94

• chloride provides functionalized homoallylic amines. An intramolecular version of this process leads to 3-aminotetrahydrofurans and 3-aminotetrahydropyrans. Keywords: allene; 3-aminotetrahydrofurans; 3- and 4-aminotetrahydropyrans; hydrozirconation; nitrile; transmetalation; Introduction The reversible

• to that of the zinca-Claisen reaction observed by Suzuki and co-workers [38]. Analogous to the previous work in our group [15], the silyl-substituted allene 16 produced the (E)-vinylsilane 17 as the sole product in this reaction. Given the success of the one-pot intermolecular reductive coupling of

• to depend on the allene substitution. The intramolecular variant of this reaction was used to prepare 3-aminotetrahydrofurans and 3-aminotetrahydropyrans, and these addition products can subsequently be transformed into synthetically valuable β-amino acid building blocks. Coupling constant analysis

A comparative study of the Au-catalyzed cyclization of hydroxy-substituted allylic alcohols and ethers

• Berenger Biannic,
• Thomas Ghebreghiorgis and
• Aaron Aponick

Beilstein J. Org. Chem. 2011, 7, 802–807, doi:10.3762/bjoc.7.91

• architectures; for recent reviews on Au-catalysis, see [2][3][4][5][6][7][8][9][10]. Generally, only mild conditions are necessary and these processes are highly chemoselective. While the typical substrates employed in these reactions effect transformations on alkyne, allene, and alkene moieties, recent reports

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• alkene or an allene, the corresponding substrates 93 and 94 underwent a gold-catalyzed rearrangement to afford indenes 95 (80%) and 96 (78%), respectively. Interestingly, only the cyclopropene reacted by ring-opening followed by Friedel–Crafts cyclization: The alkene and the allene units were unaffected

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• which rely on the activation of the allene and alkyne component. The mechanism as well as the regio- and stereoselectivity of the cyclizations are also discussed. Keywords: alkynes; allenes; gold; heterocyclizations; β-lactams; Introduction The chemistry of alkynes and allenes has been extensively

• catalyzed by gold complexes because of their powerful soft Lewis acidic nature [10][11][12][13][14][15][16]. In particular, gold-catalyzed intramolecular addition of oxygen and nitrogen nucleophiles across an allene or a carbon–carbon triple bond is intriguing from the point of view of regioselectivity

• four-membered ring, using the chirality and functionalization of the β-lactam ring as a stereo-controlling element [29][30]. This overview focuses on gold-catalyzed heterocyclization reactions of allenic and alkynic β-lactams which rely on the activation of the allene and alkyne component. The

Complete transfer of chirality in an intramolecular, thermal [2 + 2] cycloaddition of allene-ynes to form non-racemic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2011, 7, 601–605, doi:10.3762/bjoc.7.70

• Kay M. Brummond Joshua M. Osbourn University of Pittsburgh, Department of Chemistry, Chevron Science Center, 219 Parkman Avenue, Pittsburgh, PA 15260, USA 10.3762/bjoc.7.70 Abstract A thermal [2 + 2] cycloaddition reaction of allene-ynes has been used to transform chiral non-racemic allenyl

• oxindoles into chiral non-racemic spirooxindoles containing an alkylidene cyclobutene moiety. The enantiomeric excesses were determined by chiral lanthanide shift NMR analysis and the transfer of chiral information from the allene to the spirooxindole was found to be greater than 95%. Keywords: alkylidene

• cyclobutene; allene; allenyloxindole; chiral lanthanide shift reagent; chiral transfer; Introduction The [2 + 2] cycloaddition reaction of allenes and alkynes provides rapid entry into synthetically challenging alkylidene cyclobutene ring systems. We, along with others, have demonstrated the intramolecular

Gold-catalyzed regioselective oxidation of terminal allenes: formation of α-methanesulfonyloxy methyl ketones

• Yingdong Luo,
• Guozhu Zhang,
• Erik S. Hwang,
• Thomas A. Wilcoxon and
• Liming Zhang

Beilstein J. Org. Chem. 2011, 7, 596–600, doi:10.3762/bjoc.7.69

• from terminal allenes in fair to good yields. The chemistry relies on a gold-catalyzed intermolecular oxidation of the 1,2-diene unit using 3,5-dichloropyridine N-oxide as the oxidant. The reaction tolerates a range of functional groups and shows excellent regioselectivity. Keywords: allene; catalysis

• allenes could also be oxidized by these N-oxides in the presence of gold catalysts. As shown in Scheme 1B, intermediate C, likely formed via an initial nucleophilic attack of a gold-activated allene, cannot undergo elimination in the same way as intermediate A, hence gold carbene intermediate B would not

• be formed. While C may revert back to the allene substrate, we suspect that a SN2'-type reaction by an external nucleophile could facilitate the fragmentation of the O–Y bond, ultimately leading to useful products via intermediate D. Herein we report our preliminary studies, which led to a facile

Synthesis of cross-conjugated trienes by rhodium-catalyzed dimerization of monosubstituted allenes

• Tomoya Miura,
• Tsuneaki Biyajima,
• Takeharu Toyoshima and
• Masahiro Murakami

Beilstein J. Org. Chem. 2011, 7, 578–581, doi:10.3762/bjoc.7.67

• stereoselective manner to give cross-conjugated trienes, which are different from those obtained by a palladium catalyst. Keywords: allene; cross-conjugated triene; dimerization; rhodium; stereoselective; Introduction Cross-conjugated trienes, known as [3]dendralenes [1], are attractive synthetic precursors

• of cross-conjugated trienes by the allene dimerization reactiona. Supporting Information Supporting Information File 110: Experimental details and spectroscopic data for new compounds. Acknowledgements This work was supported in part by MEXT (Grant-in-Aid for Challenging Exploratory Research, No

Synthesis of chiral mono(N-heterocyclic carbene) palladium and gold complexes with a 1,1'-biphenyl scaffold and their applications in catalysis

• Lian-jun Liu,
• Feijun Wang,
• Wenfeng Wang,
• Mei-xin Zhao and
• Min Shi

Beilstein J. Org. Chem. 2011, 7, 555–564, doi:10.3762/bjoc.7.64

• NHC–Au(I) complex (S)-6a was consequently investigated as the catalyst in the asymmetric intramolecular hydroamination of allenes. This reaction has been achieved with high enantioselectivity by a chiral phosphine–Au(I) complex [87][88][89][90][91][92][93]. Treatment of allene 11 with (S)-6a and

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• higher aromatics are more likely to undergo para cycloadditions [91], and that it is the main mode when allenes are involved [92]. A high yielding example of a para photocycloaddition with an allene has been published by Haddaway et al. (Scheme 30) [93]. If the irradiation is carried out in the presence

• photocycloaddition followed by rearrangements. Stable [2 + 2] photocycloadducts. Ortho photocycloadditions with alkynes. Intramolecular ortho photocycloaddition and rearrangement thereof. Intramolecular ortho photocycloaddition to access propellanes. Para photocycloaddition with allene. Photocycloadditions of

Synthesis of 5-(2-methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene as 2,2'-disubstituted 1,1'-binaphthyls via benzannulated enyne–allenes

• Yu-Hsuan Wang,
• Joshua F. Bailey,
• Jeffrey L. Petersen and
• Kung K. Wang

Beilstein J. Org. Chem. 2011, 7, 496–502, doi:10.3762/bjoc.7.58

• Benzannulated enyne–allenes bearing an aryl substituent at the alkynyl terminus are excellent precursors of 5-aryl-11H-benzo[b]fluorenes [1][2][3][4][5]. Several synthetic pathways to the benzannulated enyne–allene systems have been reported, including generation in situ from the corresponding benzannulated

• enediynes. Specifically, treatment of the benzannulated enediyne 1a with potassium tert-butoxide in refluxing toluene for six hours promoted a 1,3-prototropic rearrangement to produce, in situ, the benzannulated enyne–allene 2a, which in turn underwent a sequence of Schmittel cascade cyclization reactions

• -protropic rearrangement to form the corresponding benzannulated enyne–allene 10a. A Schmittel cyclization reaction [1][2][3][4] generates biradical 11a, which then undergoes an intramolecular radical–radical coupling to afford 12a. This is followed by a second prototropic rearrangement to restore the

An efficient and practical entry to 2-amido-dienes and 3-amido-trienes from allenamides through stereoselective 1,3-hydrogen shifts

• Ryuji Hayashi,
• John B. Feltenberger,
• Andrew G. Lohse,
• Mary C. Walton and
• Richard P. Hsung

Beilstein J. Org. Chem. 2011, 7, 410–420, doi:10.3762/bjoc.7.53

• -closure; 1,3-hydrogen shift; isomerization; Introduction While allene isomerization to afford conjugated dienes is a well-known and thermodynamically favourable process, it is not trivial kinetically. A concerted allene isomerization leading to a diene involves a 1,3-hydrogen shift, which constitutes a

Rh(I)-catalyzed intramolecular [2 + 2 + 1] cycloaddition of allenenes: Construction of bicyclo[4.3.0]nonenones with an angular methyl group and tricyclo[6.4.0.0^1,5]dodecenone

• Fuyuhiko Inagaki,
• Naoya Itoh,
• Yujiro Hayashi,
• Yumi Matsui and
• Chisato Mukai

Beilstein J. Org. Chem. 2011, 7, 404–409, doi:10.3762/bjoc.7.52

• tricyclo[6.4.0.01,5]dodecenone framework in a satisfactory yield. Keywords: allene; bicyclo[4.3.0] derivatives; carbonylative [2 + 2 + 1] cycloaddition; quaternary center construction; rhodium; Introduction The Co2(CO)8-mediated Pauson–Khand reaction (PKR) [1][2] is well recognized as a formal [2 + 2 + 1

• allene group in the presence of several Rh(I) catalysts ([RhCl(CO)2]2, [RhCO(dppp)2]Cl or [RhCl(CO)dppp]2). We have now examined the similar ring-closing reaction using an alternative allenene 7a with a methyl group on the allenyl group for further evaluation of these reactions. According to the

• proximal double bond of the allene might be mandatory. Removal of the allylic sulfone group in 2a was achieved by tributyltin hydride in the presence of AIBN to give 9g in 91% yield [35][36][37][38][39][40][41]. Thus, the phenylsulfonyl group of 2a can be regarded as a hydrogen surrogate and this procedure

CuCl-catalyzed aerobic oxidation of 2,3-allenols to 1,2-allenic ketones with 1:1 combination of phenanthroline and bipyridine as ligands

• Shuxu Gao,
• Yu Liu and
• Shengming Ma

Beilstein J. Org. Chem. 2011, 7, 396–403, doi:10.3762/bjoc.7.51

• coordinating ability of the allene moiety. Further study in this area is being pursued in this laboratory. Experimental General experimental methods for starting materials The starting allenols 1a–e, 1i, 1k, 1l, 1m were prepared via the reaction of propargyl bromides and corresponding aldehydes in the presence

Allene chemistry

• Kay M. Brummond

Beilstein J. Org. Chem. 2011, 7, 394–395, doi:10.3762/bjoc.7.50

• continued in my first faculty position at West Virginia University, where my colleagues Professors Bob Moore (of the Doering-Moore-Skattebøl reaction) and Kung Wang (contributor to this issue) contributed greatly to my appreciation and understanding of the allene functional group. Focusing on a particular

• , creates a limitation to our knowledge of our field. This Thematic Series entitled “Allene chemistry” in the Beilstein Journal of Organic Chemistry represents contributions from leading chemists exploring a wide range of reactions involving allenes as reactants or products. The articles within detail

• discoveries surrounding the allene group and provide knowledge that chemists need in order to make informed decisions about whether or not to include an allene in a synthetic plan. I would like to thank all the authors for their contributions to this issue. Kay Brummond Pittsburgh, April 2011