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

• ]. Treatment of 20 with the sulfur ylide derived from trimethylsulfoxonium iodide [33][34] led to recovery of starting material at room temperature, but decomposition at elevated temperatures. Instead, the enone was smoothly reduced to the allylic alcohol, and a Furukawa-modified Simmons–Smith reaction [35

• around the enone. Aliphatic enones react more sluggishly in this transformation; however, 3,4,5-trimethoxyphenylboronic acid may be used as a more efficient nucleophilic partner to circumvent this limitation. Application of this transformation to the ripostatin A epoxide fragment 5 allows installation of

• the C13 hydroxy group via conjugate addition to the δ-hydroxy-α,β-enone 49 (Figure 5). Although the diastereoselectivity of this reaction using substrates with a chiral center at the hydroxy group had not been investigated in the published study, substitution at the carbinol position was reportedly

Copper(II)-salt-promoted oxidative ring-opening reactions of bicyclic cyclopropanol derivatives via radical pathways

• Eietsu Hasegawa,
• Minami Tateyama,
• Ryosuke Nagumo,
• Eiji Tayama and
• Hajime Iwamoto

Beilstein J. Org. Chem. 2013, 9, 1397–1406, doi:10.3762/bjoc.9.156

• Scheme 3) [22][24][27]. On the other hand, the same spirocyclic ketone is obtained in the 9,10-dicyanoanthracene (DCA) and biphenyl (BP) sensitized PET reaction of probe II, while reactions of this substrate with certain oxidants afford ring-expanded ketone and enone products (right in Scheme 3) [23][25

• presence of Cu(OAc)2 [25]. Only a trace amount of ring-expanded enone 4 along with small amounts of desilylated alcohol 1b (ca. 8%) and ketone 5 were detected in the product mixture by using 1H NMR analysis. Treatment of 1a (0.19 mmol) with n-Bu4NF (2.0 equiv) in THF for 1 h followed by hydrolysis gave a

• summarized in Table 1. As expected, this process produces ketone 3 as the major product along with both 2 and ring-expanded enone 4 as minor products. Moreover, the order of addition of 1b and Cu(OAc)2 does not significantly affect the product distribution (compare Table 1, entry 1 to entry 2). An

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• Aleksey I. Gerasyuto Zhi-Xiong Ma Grant S. Buchanan Richard P. Hsung Division of Pharmaceutical Sciences, School of Pharmacy, and Department of Chemistry, University of Wisconsin, Madison, WI 53705, USA 10.3762/bjoc.9.131 Abstract A successful enone version of an intramolecular aza-[3 + 3

• expand the scope of the enone aza-[3 + 3] annulation was made in the form of propyleine synthesis as a proof of concept. While synthesis of the enone annulation precursor was successfully accomplished, the annulation proved to be challenging and was only modestly successful. Keywords: alkaloids

• ][63], and tubulosine [64]. With the appropriate choice of an R group in the synthetic design, a highly convergent and expedient strategy can come forth for constructing these alkaloids. We report herein our success in achieving intramolecular aza-[3 + 3] annulations of an enone. Results and Discussion

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• enantioselectivity and short reaction time, we decided to pursue this conversion at 40 °C where we obtained an enantiomeric excess of 90% (70% yield after 14 days). The enantiomerically enriched Hajos–Wiechert-like diketone 8 (ee > 90%) was then subjected to a selective protection of the C-6 enone motif to yield

• enone 10 (>10 grams) for further functionalization. Conversion of 10 to 9 was accomplished based on our previously reported strategy (Scheme 3) [25]. Treatment of 10 with magnesium methyl carbonate (MMC) [79][80][81] yielded the C-5 carboxylic acid that, without further purification, was esterified

• (0)-catalyzed carbomethoxylation [87][88][89][90] produced the desired C-ring lactone 20 in 61% yield. Epoxidation of the C-6/C-7 enone with NaOH/H2O2 followed by oxidative cleavage of the C-11 terminal alkene under OsO4/NaIO4 conditions [91][92] afforded the corresponding C-11 aldehyde. Exposure of

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• (1.5 equiv) in EtOH effected cyclization, but the yield of 5a was poor due to the concomitant formation of carbamate 9 (39%) and enone 10 (30%) (Table 1, entry 1). This was in marked contrast to the observation that the same reagent system, i.e., FeBr2 (0.5 equiv)/Bu4NBr (1.2 equiv), allowed the

• provided evidence that these byproducts were generated by the intramolecular cyclization of enone 10 with TMSCl in EtOH, suggesting that the FeCl2/TMSCl system also gave enone 10 in ca. 30% yield [37]. The present study on the aminohalogenation reaction of carbamate 8 has inspired mechanistic insights that

• deserve discussion (Scheme 4). We hypothesize that cyclized material 5a/5b, reduced material 9, and enone 10 are generated from an N–iron complex (i) that has free-radical character, as previously proposed in the catalytic cyclization of azidoformates [30][38][39][40]. The contrasting yields obtained from

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

• by the preparation of enone 81 from allylic alcohol 80 in Scheme 17. By varying the xanthate partner, different substitution patterns and rings may then be introduced. Two examples, 83 and 86, in Scheme 17 illustrate the formation of triquinanes via bicyclic intermediate xanthates 82 and 85. The

• ]. In the sequence displayed in Scheme 18, the addition–cyclisation of a malonyl radical to enyne 89 furnishes allenyl acetate 91 by cyclisation of propargyl radical 90 [41]. Compound 91 readily undergoes reductive dexanthylation and solvolysis into enone 92, and internal Michael addition to give

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• ester moiety to a Weinreb amide [18] followed by changing the nitrogen protecting group to a carbamate furnished the key intermediate 6, which could be further alkylated with Grignard reagents to give β’-amino protected α,β-enone 1 in good overall yield and high enantiomeric excess. As Grignard reagents

Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• the primary amino group. The most promising counter ions are expected to be from the first group of the periodic table of elements, and test reactions were carried out by employing catalyst 5 and 7 with benzylideneacetone (9) and cyclohex-2-enone (10) (Figure 2) as substrates (Table 1). It was found

• % whereas the trans-diaminocyclohexane derivatives could only reach up to 47% ee (Table 1, entry 5). There is a strong preference for 7 to produce higher ee’s if cyclic enones are used, whereas diaminocyclohexane derivatives perform better with the acyclic trans-enone 9 (Table 1, entry 4 versus Table 2

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• ) [26]. Asymmetric induction can be achieved in [2 + 2] cycloadditions through the use of a chiral auxilliary. The [2 + 2] reaction shown in Scheme 3 employed a chiral ester function to direct the facial selectivity of the addition of the enone to cyclopentene. Diastereoselectivity was found to be

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• -containing esters could be the aromatic nature of the squaramide functional group in catalyst IX, allowing additional π–π-interactions. The properties of the enone double bond of the substrate depend on the nature of the substituents in the phenyl ring. Therefore, the electronic effect of the para

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• benchmarking. As a rough indication of activity, we started out by investigating quinine (1) and supported catalyst 10a–d in the Michael addition of 3-methoxythiophenol and cyclohex-2-enone (Table 1) [17]. Although the performance of quinine in this reaction is poor with regards to selectivity (providing only

• supported thiourea catalyst 12 in the Michael addition of thiophenol and cyclohex-2-enone [17], a transformation known to be very efficiently catalysed by the free thiourea catalyst 3 (Table 3) [19][20]. The immobilized catalyst 12 proved highly active (the uncatalysed reaction is very slow), rapidly giving

• CH2Cl2 (70 mL) for 12 h, and the purified beads were left to dry at room temperature for 24 h (62% yield). Catalyst loadings were determined by CHN analysis. General procedure for asymmetric Michael addition of 3-methoxythiophenol to cyclohex-2-enone: 3-Methoxythiophenol (0.30 mL, 3.10 mmol), and

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• mutants and mutasynthetic approaches. We suggest that the formation of these derivatives is based on elimination at C-7/C-8 followed by reduction(s) of the intermediate enone. In bioactivity tests, only ansamitocin derivatives bearing an ester side chain at C-3 showed strong antiproliferative activity

• ). Indeed, the expected deoxygenated product 13b could be detected, but was also accompanied by the formation of alcohol 9b. Compound 9b may either have resulted from Michael addition of water to the suspected intermediate enone 17 (see later in Scheme 5) or from hydrolytic cleavage of the carbinolamide 12

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• central problem we wished to address was the preparation of the 3-alkyl-2-pyridone moiety of 36 by an unusual [3 + 3] construction developed in our laboratory [80]. This chemistry (Scheme 7) promotes the condensation of a cyanoacetamide 37, with an enone or enal 38, in the presence of t-BuOK in DMSO

Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, two potent new microtubule-stabilizing agents

• María Jiménez,
• Wei Zhu,
• Andreas Vogt,
• Billy W. Day and
• Dennis P. Curran

Beilstein J. Org. Chem. 2011, 7, 1372–1378, doi:10.3762/bjoc.7.161

• , we turned to the initial fragment couplings as summarized in Scheme 4. Fragments 7 and 8 were first combined by a proven sequence starting with an HWE reaction mediated by Ba(OH)2 [42] to provide enone 22 in good yield (80%). This enone was then treated with Stryker’s reagent [43] to selectively

Cyclization of 5-hexynoic acid to 3-alkoxy-2-cyclohexenones

• Anne T. Hylden,
• Eric J. Uzelac,
• Zeljko Ostojic,
• Ting-Ting Wu,
• Keely L. Sacry,
• Krista L. Sacry,
• Lin Xi and
• T. Nicholas Jones

Beilstein J. Org. Chem. 2011, 7, 1323–1326, doi:10.3762/bjoc.7.155

• can be found in Supporting Information File 1. Additional evidence for the participation of chloride ion in this reaction was given by the isolation of the known 3-chloro-2-cyclohexenone (4) [11] from reactions that involved sterically hindered alcohols such as tert-butanol (Table 2). Enone 4 was

One-pot Diels–Alder cycloaddition/gold(I)-catalyzed 6-endo-dig cyclization for the synthesis of the complex bicyclo[3.3.1]alkenone framework

• Boubacar Sow,
• Gabriel Bellavance,
• Francis Barabé and
• Louis Barriault

Beilstein J. Org. Chem. 2011, 7, 1007–1013, doi:10.3762/bjoc.7.114

• ][22]. Results and Discussion The synthesis began by a C-alkylation of enone 8 [23] using LDA and MeI to give the corresponding ketone in 90% yield (Scheme 2). A second alkylation to add the propargyl chain was carried out using LDA and propargyl bromide to afford 9 in 62% yield as an inseparable

• steps from enone 8. However, one might recognize that the low chemical yields encountered in some steps undermine the efficacy of the Au(I)-catalyzed cyclization approach. In order to solve this issue, we assumed that bicyclo[3.3.1]nonenone scaffolds can be directly obtained through an intermolecular

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• , such that a consecutive cyclopropyl ring expansion affords the bicyclic [3.2.0]heptane skeleton 68 in excellent yield and selectivity [53]. Treatment of 68 with a protic acid in water should activate the enone system triggering the nucleophilic attack of water to give hydroxy ketones 69. The synthetic

• pivalate quantitatively. In situ hydrolysis and subsequent equilibration with NaOMe/MeOH yielded thermodynamically favored ketone 97 in 68% yield and >90% ee. Since this bicyclic enone has been recently elaborated to frondosins A and B [60][61] this approach represents a streamlined formal enantioselective

A racemic formal total synthesis of clavukerin A using gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes as the key strategy

• Jae Youp Cheong and
• Young Ho Rhee

Beilstein J. Org. Chem. 2011, 7, 740–743, doi:10.3762/bjoc.7.84

• developed by us [15]. This reaction provides cycloheptane frameworks in a unique manner and illustrates the utility of the gold-catalyzed reactions [16][17][18][19][20][21][22][23]. From a retrosynthetic point of view, we envisioned two different approaches to the key enone intermediate 1 [3] to clavukerin

• A, starting from the cycloheptenone 4 (Scheme 1). In the first approach, enone 1 could be prepared by the sequential cyclization and the chemo- and stereoselective hydrogenation from cycloheptenone 4 (path A). Alternatively, enone 1 could be accessed by the hydrogenation of 4 and the subsequent

• in the formal synthesis of clavukerin A was explored. We first investigated the cyclization–hydrogenation strategy (path A in Scheme 4). Deprotection of 4 and the aldol condensation of the resulting diketone under basic conditions proceeded smoothly to give the enone 2 in good yield. However

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• conjugated enone substructure has attracted the interest of synthetic chemists for decades. Among numerous methodologies, aldol condensations and Wittig-type reactions have been widely utilized [9][10][11][12][13][14][15][16][17][18]. Recently, it was found that conjugated enones could be generated from the

• investigated in this reaction, and the corresponding enone products 2 were isolated in good yields. They employed the alkyne–carbonyl metathesis in the preparation of fused ring systems and obtained two six-membered bicyclic products. However, if the original ring was five- or eight-membered, the reaction

• intermediate, which then generates an oxetenium intermediate. After several electron transfer steps, the cyclic enone product is formed. A similar [2 + 2] pathway has also been invoked for the Brønsted acid- or Lewis acid-mediated intramolecular and intermolecular alkyne–aldehyde metatheses. If terminal

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• of the enantiomers of hindered enone 46 by addition, oxidation and elimination of a sulfenic acid under basic conditions (Scheme 18) [45]. Xiao and co-workers developed an organocatalytic process for the addition of thiols to nitroalkenes [46]. Using thiourea organocatalyst 48, conjugate addition of

• of enone 46. Organocatalytic conjugate addition to nitroalkenes 49. Preparation of β-amino acid 54. Sulfur migration within oxazolidine-2-thiones 56. Preparation of thiols 62 by self-regeneration of stereocentres. Synthesis of (5R)-thiolactomycin. Preparation of tertiary thiols and thioethers via α

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

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

• dianthryls. Photocycloaddition of enone with benzene. Intramolecular photocycloaddition affording multicyclic compounds via [4 + 2]. Photocycloaddition described by Sakamoto et al. Proposed mechanism by Sakamoto et al. Photocycloaddition described by Jones et al. Proposed mechanism for the formation of

Molecular rearrangements of superelectrophiles

• Douglas A. Klumpp

Beilstein J. Org. Chem. 2011, 7, 346–363, doi:10.3762/bjoc.7.45

• . This suggests charge–charge repulsive effects in this system. When camphor (44) is reacted with HF-SbF5, three products are isolated (Scheme 10) [22]. A mechanism is proposed for conversion of ketone 45 to enone 47. Initially, the carboxonium ion 45a is formed by protonation of the carbonyl oxygen. A

• formation of a tertiary-carbenium ion 45c which ultimately leads to the stable enone structure 47. When 2-cyclohexen-1-one (47) is reacted with HF-SbF5, a ring contraction occurs to give 3-methyl-2-cyclopenten-1-one (50, Scheme 11) [23]. This conversion involves diprotonation of 48 to give a

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, C_nH_n and closo-boranes [B_xH_x]²⁻

• Michael J. McGlinchey and
• Henning Hopf

Beilstein J. Org. Chem. 2011, 7, 222–233, doi:10.3762/bjoc.7.30

• been proposed that an intermediate in the synthesis of [5]peristylane may be a viable precursor to the still unknown D3h [43.56]nonahedrane, (13). As shown in Scheme 12, the diene-dione 63 can be readily converted to the double enone 64 which undergoes [2 + 2] photocyclization to yield the pentacyclic

Synthesis of 2a,8b-Dihydrocyclobuta[a]naphthalene-3,4-diones

• Kerstin Schmidt and
• Paul Margaretha

Beilstein J. Org. Chem. 2010, 6, No. 76, doi:10.3762/bjoc.6.76

• -diones, i.e. (formal) 1,2-naphthoquinone + alkyne [2 + 2] cycloadducts. Results Irradiation of 1 in the presence of alkynes affords the – known [3] – pentacyclic dimers and variable amounts (0–33%) of enone + alkyne cycloadducts as indicated by 1H NMR spectroscopy. The yields of mixed cycloadducts with

• (relatively) low yield of mixed cycloadduct formation from excited 1 and alkynes seems disappointing. Nevertheless, one should bear in mind that a) dimer formation on irradiation of phenyl-conjugated enones, e.g., 3-phenylcyclohex-2-enone, is not suppressed even in neat alkenes as solvent [6], as these

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33