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

• primary alcohol of the side chain was oxidized with Dess–Martin periodinane (DMP) to give aldehyde 183. The latter was subsequently reacted with trimethylsilyl ketene acetal 184 in the presence of oxazaborolidinone 185 to afford aldol product 186 and the C22-epimer as only isomers in a 1:1 mixture. Dess

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• ) the formation of the monoadducts 8a,c proceeds via the formation of zwitterionic intermediates 7a,c by nucleophilic attack of the azirine nitrogen lone pair on the C=O group of the ketene fragment of intermediate 6a. Interaction of monoadducts 8a,c with ketene 6a leads to the formation of the unstable

• zwitterionic intermediates 9a,c which further cyclize to bisadducts 3a,c. The barriers for addition of the azirine and aziridine nitrogen lone pair of 1a,c, and 8a,c to ketene 6a increase in passing from compounds 1a, 8a to compounds 1c, 8c, because of a decrease in the nucleophilicity of the latter due to the

• , to give derivatives of 1,3-oxazines [34][35][36]. Another route to compounds 4 and 5 could, therefore, involve interaction of dihydropyrazine 11 with ketene 6, leading to the monoadduct 12, which further reacts with a second molecule of 6 to give 2:2 adducts 4 and 5 (Scheme 3, (b)). To evaluate the

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -groups to olefinic acid by either asymmetric epoxidation, dihydroxylation or aminohydroxylation [10][11][12][13][14][15], (ii) the asymmetric synthesis of β-lactams by a Staudinger reaction between ketene and imine to give the corresponding amino acids [16], and (iii) the Lewis acid catalyzed

• multicomponent condensation reactions of aldehyde, an amine and ketene silyl acetal derivatives to get the vicinal hydroxylamino acids [17]. In addition, a few strategies employ a chiral pool approach. For example, Wee et al. utilized the zinc-silver-mediated reductive elimination of α-D-lyxofuranosyl

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• esters [6][7][8][9][10]. Up to now, a series of nucleophilic substrates have been reported to react with α-imino esters, such as enamine [11][12][13][14], carbamate ammonium ylide [15], 1,3-dipolar cycle [16], boronic acid [17], acetylide [18], proparygylic anion [19] and ketene silyl acetal [20]. These

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• the outcome of the sequence. The latter hypothesis of the iminium-ion stabilization obviously influences the lifetime of the zwitterion 13. Furthermore the enamine formed by deprotonation of 9 is a S,N-ketene acetal, which is significantly more nucleophilic than Fischer’s base (7). The higher

• the dipolar intermediate, which is responsible for the bifurcation as supported by computational studies, enamine nucleophiles favorably lead to 1-styryleth-2-enylideneindolones diastereomers for N-methyl-substituted anilides. The S,N-ketene acetal derived from dimethyl benzothiazolium favors the

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

• between isoquinolinium-2-ylamide 43 and keteneimine 57 [79], silver salt plays the usual role of a π-philic catalyst, whereas ketene imine 57 is generated by a well-known procedure involving a copper(I)-catalyzed azide–alkyne [3 + 2] cycloaddition (CuAAC) giving rise to 5-cuprated triazole intermediate 56

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• ketene incorporated KOH to afford the potassium salt of 1,1,3,3-tetramethylindan-2-carboxylic acid (the product of a formal hydrolysis). The lithium salt of this key acid is able to acylate aryllithium compounds, furnishing one-sidedly overcrowded ketones along with the corresponding tertiary alcohols

• expulsion of the observed Me2S. The resultant, still unknown di-tert-alkyl ketene 18 appears to have only limited options in this milieu: Taking t-Bu2C=C=O [2] as a model of the slightly less congested ketene 18, a Pummerer-type acylation of DMSO by 18 should require the assistance of a carboxylic acid [33

• with the base-induced O–S bond cleavage during the Pummerer acylation with t-Bu2C=C=O [36], a base-induced decay of 28 can be expected to generate the 2-thioniapropene 29 along with the α-chloroenolate 30 that may produce the ketene 18 (or the unknown acyl choride) and finally (as in Scheme 3) the

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

• pseudo-axial to avoid allylic A1,2-strain, the sigmatropic rearrangement occurred via a pseudo-axial attack of the silyl ketene acetal on the double bond in the cyclohexene ring. These results are in accordance with the observations of Ireland et al. [49], who examined the propensity for axial versus

• , entry 1). Intermediary, the silyl enol ether and the silyl ketene acetal are formed. However, after the rearrangement, the keto-functionality can be set free again during an acidic work-up. In terms of yield and diastereoselectivity there was no difference observed between rearrangements with

• deprotection, esterification and MOM protection. The Ireland–Claisen rearrangement proceeded smoothly and gave a ca. 1.3:1 (78:79) mixture of diastereomers with the product resulting from the pseudo-axial attack of the silyl ketene acetal being the major diastereomer. In analogy to the results above the

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

• [199] upon treatment with silver benzoate. The intermediate ketene 235 underwent stereospecific DVCPR through transition state 235' under the reaction conditions to give enone 236 in excellent yield. This constituted the first example of the direct formation of an enone through a DVCPR. Stephenson and

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• careful filtration of the desiccant, the dichloromethane solution of the imine was used in further reactions without purification or separation of unreacted amine or the enamine side product. Ketene imine cycloaddition reactions of α-SF5-substituted aldimines and ketimines Dropwise addition of the crude

• imine 5 resulted only in decomposition. Excess amine 4 that was present was acylated by benzyloxyacetyl chloride to form the corresponding amide. The utility of the ketene–imine cyclization was not limited to aldimines. The addition of SF5Br to the enol acetate of ethyl pyruvate 9 formed ethyl

• been optimized. But the significance of these findings lies not only in the difference in reactivity in comparison with trifluoropropanaldimine but also in the relative diastereoselectivity of the ketene–imine cycloaddition reaction in comparison with the other reactions of SF5-bearing aldehydes [16

Reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithiethane with N-vinyl compounds

• Viacheslav A. Petrov and
• Will Marshall

Beilstein J. Org. Chem. 2013, 9, 2615–2619, doi:10.3762/bjoc.9.295

• sulfides, cyclic dienes and styrenes [1][2], fluoride anion-catalyzed reactions of compound 1 with vinyl ethers [1][3][4], vinyl sulfides [3], ketene dimethylacetal [5], styrenes [6][7], cyclic dienes [8] and quadricyclane [9]. At this point, no data for the reaction of HFTA or HFTA dimer with vinylamines

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• rearrangement was then carried out by using silver nitrate in THF to give the intermediate ketene which was trapped with N,O-dimethylhydroxylamine to provide the corresponding Weinreb amide 1 in 84% yield over two steps. In the next step, the Weinreb amide 1 was added to a solution of O-protected 1-hexynol

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• afforded the five-membered ring product using either lithium methoxide or 2,6-lutidine as a base. Clearly, decarboxylation of the carboxylate anion was not a problem. In fact, cyclic voltammetry data suggest that the reaction originated from an oxidation of the ketene dithioacetal. The oxidation potential

• solution. The carboxylate was only partially soluble in acetonitrile. While the formation of the carboxylate significantly lowered the oxidation potential of the acid moiety, it did not lower it close to the oxidation potential measured for substrate 14a or even the oxidation potential of a ketene

• dithioacetal (ca. +1.06 V versus Ag/AgCl) [21]. Hence, the oxidation potential measured for 14a is most consistent with a fast cyclization originating from oxidation of the olefin. Fast cyclization reactions are known to significantly lower the oxidation potential of a ketene dithioacetal. For example, the

Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles: a novel approach

• Sandeep Kumar,
• Ramendra Pratap,
• Abhinav Kumar,
• Brijesh Kumar,
• Vishnu K. Tandon and
• Vishnu Ji Ram

Beilstein J. Org. Chem. 2013, 9, 809–817, doi:10.3762/bjoc.9.92

• of the weak noncovalent interactions operating in the supramolecular architectures of alkenylated indoline-2-ones and to explain the relative stability of one of the tautomers with respect to the others. Keywords: alkenylation; dibenzo[d,f][1,3]diazepin-6(7H)-one; indolin-2-one; ketene dithioacetal

• [9] activities. In addition, they also act as inhibitors of lipoxygenase and butyrylcholinesterase enzymes [10]. While alkylations and arylations of indole are well documented in the literature [11][12][13][14][15][16][17][18][19], acid-catalyzed alkenylation by α-oxo ketene dithioacetals [20] have

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

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• conjugate additions of nucleophiles [23][24][25][26][27][28]. Kinetics of the reactions of the iminium ion 3a with the silylated ketene acetal 7a [35]. Laser flash photolytic generation of iminium ions 3a. Correlations of the reactivities of the iminium ions 3a and 3b toward nucleophiles with the

• °C, silyl ketene acetal 7b in dichloromethane with c(3a-CF3CO2) = (1.7–2.5) × 10−5 M, kryptopyrrole 12a in acetonitrile with c(3a-CF3CO2) = 5.0 × 10−5 M). Comparison of calculated and experimental rate constants of electrophilic aromatic substitutions with iminium ions [56]. Aza-Michael additions of

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

• 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

• cycloadditions proceeded with complete regio- and stereoselectivity with respect to the olefin 1, but less so with respect to the ketene 3 (Table 1), such that endo-4 and exo-4 isomers were formed in variable amounts, depending on the nature of the substrates. In general, the conversions of cyclopenta-1,3-diene

• substitution patterns at both the ketene and the olefin moiety were compatible with this ring-opened method. Thus, cyclobutanones carrying both vinyl (Table 3, entries 1–14) and phenyl (Table 3, entries 15–18) substituents underwent the cleavage reaction. The monocyclic butanone 4g was also tolerated to give

Synthesis, solid-state fluorescence properties, and computational analysis of novel 2-aminobenzo[4,5]thieno[3,2-d]pyrimidine 5,5-dioxides

• Kenichirou Yokota,
• Masayori Hagimori,
• Naoko Mizuyama,
• Yasuhisa Nishimura,
• Hiroshi Fujito,
• Yasuhiro Shigemitsu and
• Yoshinori Tominaga

Beilstein J. Org. Chem. 2012, 8, 266–274, doi:10.3762/bjoc.8.28

• -dioxides (3a–g), 2-amino-4-methylsulfanylbenzo[4,5]thieno[3,2-d]pyrimidine (6), and 2-amino-4-methylsulfanyl-7-methoxybenzo[4,5]furo[3,2-d]pyrimidine (7), were synthesized in good yields from heterocyclic ketene dithioacetals (1a–c) and guanidine carbonate (2a) or (S)-methylisothiourea sulfate (2b) in

• , we prepared new pyrimidine derivatives, which have solid-state blue fluorescence, by means of a one-pot synthesis, involving the reaction of ketene dithioacetals, amines, and guanidine carbonate in pyridine [5]. We have also reported the one-pot synthesis of a new, fluorescent, fused pyrimidine

• derivative 2,4-diaminoindeno[1,2-d]pyrimidin-5-one; this pyrimidine derivative, which was synthesized by heating a ketene dithioacetal, 2-[bis(methylsulfanyl)methylidene]indan-1,3-dione, under reflux with amine and amidine derivatives in pyridine solution, showed blue-green fluorescence in the solid state [6

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

• elimination. This münchnone is in equilibrium with its ketene isomeric form 6, and a formal [2 + 2] cycloaddition with a second equivalent of imine generates the lactam (Scheme 3). The authors pointed out that the trapping of HCl by a sterically hindered base (NEtiPr2) is the key point in this methodology to

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• amino group (Scheme 24) [66]. Ketene dithioacetals 86 were utilized for the synthesis of corresponding pyrazole carbodithioates 88 by cyclization with methyl- or benzylhydrazine carbodithioate 87 in ethanolic TEA at room temperature. As before, the reaction proceeds via the nucleophilic substitution of

• corresponding 5-amino-3-arylamino-1-phenylpyrazole-4-carboxamides 90 (Scheme 25) [67]. Ketene S,S- and S,N-acetals or tetracyanoethylene 91 on reaction with 3-hydrazino-6-(p-tolyl)pyridazine afforded the 5-amino-4-cyanopyrazoles 92 (Scheme 26) [68]. Several thiazolylpyrazoles 97–100 bearing a variety of

• temperature, followed by treatment with methyl iodide afforded the novel ketene N,S-acetal 149. Reaction of 149 with hydrazine in refluxing ethanol gave the corresponding 5-aminopyrazole derivative 150. The reaction proceeds in the usual manner, i.e., loss of methylthio group by nucleophilic attack of

Heavy atom effects in the Paternò–Büchi reaction of pyrimidine derivatives with 4,4’-disubstituted benzophenones

• Feng-Feng Kong,
• Jian-Bo Wang and
• Qin-Hua Song

Beilstein J. Org. Chem. 2011, 7, 113–118, doi:10.3762/bjoc.7.16

• Paternò–Büchi reaction, spin-transition processes would be affected, and this may lead to interesting results. Abe et al. [14] investigated the effect of a sulfur atom on the stereoselective formation of oxetanes in Paternò–Büchi reaction of aromatic aldehydes with silyl O,S-ketene acetals to give trans-3

• -siloxyoxetanes and found that this was ca. 70/30 to 90/10. The trans-selectivity is explained by the sulfur atom effect in the silyl O,S-ketene acetal which controls the approach direction of the electrophilic oxygen of triplet n,π* aldehyde to the nucleophilic alkene. A fast ISC process of the triplet 1

Stereoselective synthesis of four possible isomers of streptopyrrolidine

• Debendra K. Mohapatra,
• Barla Thirupathi,
• Pragna P. Das and
• Jhillu S. Yadav

Beilstein J. Org. Chem. 2011, 7, 34–39, doi:10.3762/bjoc.7.6

• diastereomers 8a and 8b in a 3:2 ratio (as determined by NMR) (Scheme 2). Diastereomers 8a and 8b were easily separated by standard column chromatography on silica gel. The pioneering work on catalytic aldol reactions recently reported by Shibasaki [31] prompted us to investigate whether the ketene silyl acetal

• could be utilized for the aldol reaction in the presence of different Lewis acids to obtain a better selectivity particularly for (R)-tert-butyl (1-oxo-3-phenylpropan-2-yl)carbamate (6). To our surprise, when the reaction was carried out with the ketene silyl acetate at −78 °C, of the five Lewis acids

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

• products [2]. Very recently we reported the use of 1,2-dihydro-1,1-dimethoxynaphthalen-2-ones 1 as protected precursors for the synthesis of both photocyclodimers and ketene-photocycloadducts of 1,2-naphtoquinones [3][4]. Here we report the preparation of – novel – 2a,8b-dihydrocyclobuta[a]naphthalene-3,4

Acid catalyzed cyclodimerization of 2,2-bis(trifluoromethyl)-4-alkoxy-oxetanes and -thietanes. Synthesis of 2,2,6,6-tetrakis(trifluoromethyl)-4,8-dialkoxy-1,5-dioxocanes and 3,3,7,7-tetrakis(trifluoromethyl)-9-oxa-2,6-dithia-bicyclo[3.3.1]nonane

• Viacheslav A. Petrov and
• Will Marshall

Beilstein J. Org. Chem. 2010, 6, No. 46, doi:10.3762/bjoc.6.46

• bis(trifluoromethyl)ketene and ethyl vinyl ether [9][10]. In the case of oxetane 1d, the main channel of the reaction involves stabilization of intermediates A and B by H+ elimination, leading to the formation of olefins 2d and 2e, respectively. Such a distinct difference in the reactivity of 1d may

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• it into a silyl enol ether 9. Silyl enol ethers and ketene acetals are known to add effectively to pyridinium species in an intermolecular manner [42][43][44][45][46]. Thus 7 was converted to silyl enol ether 9 in excellent yield under standard conditions. A single geometrical isomer was obtained

• chloroformate to activate the pyridine without competing attack by the enolate. Next we extended the reaction to the cyclisation of a δ-nicotinyl butyrate ester 12 encouraged by the observations of Onaka [47], who demonstrated that silyl ketene acetals can be added (in an intermolecular fashion) to electron

• mixture of dienes 11 gave ester 12 after hydrogenation (Scheme 4). It proved challenging to isolate cleanly the silyl ketene acetal derived from 12, so instead we decided to form and cyclise the silyl derivative in a single pot. Thus, ester 12 was added to LDA at −78 °C, and the enolate quenched with