Switching the reaction pathways of electrochemically generated β-haloalkoxysulfonium ions – synthesis of halohydrins and epoxides

• Akihiro Shimizu,
• Ryutaro Hayashi,
• Yosuke Ashikari,
• Toshiki Nokami and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2015, 11, 242–248, doi:10.3762/bjoc.11.27

• part of the resulting sulfur ylide abstracts a proton attached to the carbon adjacent to the oxygen to give α-bromoketone 4a-Br by the Swern–Moffatt-type oxidation mechanism [23][24][25][26][27]. On the other hand, the hydroxide ion attacks the sulfur atom in 3a-Br and cleaves the S–O bond to give the

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• opening and generation of the benzimidazolium N-ylide 7 by the action of the alkoxide. The benzimidazolium N-ylide 7 reacts with the activated alkynes 3 to give the corresponding primary cycloadduct dihydropyrrolo[1,2-a]benzimidazoles 8. The formation of pyrrolo[1,2-a]quinoxalin-4-ones 4 involves the

Synthesis of 2-trifluoromethylpyrazolo[5,1-a]isoquinolines via silver triflate-catalyzed or electrophile-mediated one-pot tandem reaction

• Xiaoli Zhou,
• Meiling Liu,
• Puying Luo,
• Yingjun Lai,
• Tangtao Yang and
• Qiuping Ding

Beilstein J. Org. Chem. 2014, 10, 2286–2292, doi:10.3762/bjoc.10.238

• pyrazolo[5,1-a]isoquinoline derivative 3a instead of the isoquinoline-based azomethine ylide [28] was obtained in good yield (84%, Table 1, entry 1). Similar yields were obtained when NaHCO3 or K2CO3 were used as base (83% and 86% yield, respectively, Table 1, entries 2 and 3). Several other inorganic or

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

• substrates favored the formation of the products. Based on control experiments and aforementioned results, Barbas and co-workers proposed a plausible mechanism and suggested that the high stereoselectivity resulted from steric interactions between the bulky substituent of the phosphonium ylide from the MBH

• proposed that the major enantiomer formed through re-face attack of the ylide onto the Michael acceptor, rather than attack from the sterically hindered si-face. 2.16 Michael additions Asymmetric Michael addition is one of the most studied enantioselective processes in organic synthesis, with many

• ylide intermediate. Subsequent proton transfer and β-elimination of the phosphine catalyst results in a γ-functionalized α,β-unsaturated enoate. The reaction, known as γ-umpolung addition, was reported by Trost [100] and Lu [101] in 1994 and 1995, respectively. Trost employed butynoates, which are

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• olefination using (methylidene)triphenylphosphorane ylide and final hydrolysis of the acetonide provided the desired C5-substrate 30. The synthesis of substrates 24–28 bearing an allylic hydroxy group is pictured in Scheme 3. At first, the ester group of previously prepared intermediate E-17 was reduced using

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• diazo esters B involved an isoxazolium N-ylide intermediate C formed by an attack of the rhodium carbenoid onto the isoxazole nitrogen. Furthermore, ylide C could undergo either a 1,2-shift to directly generate oxazine E or a ring opening to 1-oxa-5-azahexa-1,3,5-triene D, followed by a 6π

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

• polyoxin C hydrochloride 105*HCl (Scheme 44) [121]. The reaction cascade involved thermal formation of the corresponding azomethine ylide from substrate 105*HCl and benzaldehyde, followed by 1,3-dipolar cycloaddition of the ylide to N-methylmaleimide. The formation of compound 107 as the only product was

• rationalized using semi-empirical calculations. In the same contribution, the cascade reactions starting from uracil polyoxin C 106 were described (Scheme 44). Decarboxylative formation of azomethine ylides from 106 and an aldehyde (or ketone), followed by reaction of the ylide with maleimide afforded mixtures

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• ] cycloadditions, the reaction with azomethine ylides has found great popularity, because it leads to versatile pyrrolidine derivatives of C60. The sources of the ylide can be iminium salts, aziridines, oxazolidines or silylated iminium compounds. In 1993, Prato and coworkers developed the protocol that is now

• used most commonly [31][32]. In the first step, an N-substituted amino acid (e.g., N-methylglycine) reacts with an aldehyde or ketone to generate an azomethine ylides in situ. Trapping of the ylide by a fullerene provides a fullerene-pyrrolidine derivative (8), as illustrated in Scheme 1. In light of

• the great electrophilicity of circumtrindene in the Bingel–Hirsch reaction, it came as no surprise that circumtrindene can act as a good dipolarophile in a [3 + 2] cycloaddition reaction as well. Accordingly, the azomethine ylide 23 generated in situ from N-methylglycine and formaldehyde adds to

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• ). The mechanism can be rationalized by formation of an ylide by 1,7-H-shift from the mesomeric betaine III, followed by ring cleavage of the indazole ring and subsequent ring-closure of the resulting 1,6-dipole to give the quinazolines 16a–d. Single crystals of 16b suitable for an X-ray analysis were

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

• electron withdrawing effect of the nitro group. As for possible routes for the formation of adducts 4 and 5, the first (Scheme 2, (a)) involves cleavage of the aziridine ring of intermediate 8 to generate azomethine ylide 10, and further “dimerization” of the latter. Examples of compounds that can be

• , benzene (PCM)), respectively, that far exceed the barriers to reactions leading to compound 3. These do not allow the possibility that azomethine ylide 10 can be a probable intermediate in the formation of adducts 4 and 5. It has been known that imines react with acylketenes, generated from furandiones

• [41][43][46]. It was found that water [37], Brønsted [44][48] and Lewis acids [40][41][43] facilitate the formation of pyrazine derivatives. 2H-Azirines undergo ring opening on electronic excitation to give nitrile ylides [50]. Nitrile ylide formation under thermal conditions even from such strained

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• ]. The intermediate, a phosphaza ylide (1, Scheme 1a) is readily formed with loss of nitrogen gas, while subsequent hydrolysis yields the corresponding amine and phosphine oxide. A variant of this reaction is the Staudinger ligation [4], a bioorthogonal reaction that has become an important tool of

• nucleophilic nitrogen of the resulting phosphaza ylide (3). After methanol loss and hydrolysis the reaction proceeds to amide bond formation with concomitant phosphine oxidation and formation of 4 in aqueous environment. The ligation proceeds via a cyclic intermediate (Scheme 1b) which has been isolated and

• -azidopropylamino)-6-deoxy]-β-CD were mixed in an NMR tube at 60 °C with dry CDCl3 and dry DMF-d7 where both reactants were completely soluble and the evolution of the 31P NMR signals was monitored with time. The formation of an intermediate, most likely a phosphaza ylide was evidenced by a signal at 19.8 ppm [7

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

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• respective methyl ester ylide 26 [25][26]. The reaction of phosphorane 24 with 11 under neutral conditions at 50 °C gave the desired diene 9a in very good 88% yield and in nearly perfect E-selectivity. The protection groups were removed from 9a under the previously established conditions to finally give

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

• diastereoisomeric 1,2-dihydroisoquinolines 40 (Scheme 22) [60]. Iminium intermediate 28, generated in situ from the aldimine 27 under silver triflate catalysis is the usual electrophilic intermediate, whereas the nucleophile, in this case, is the oxonium ylide 39. The reaction resulted in the synthesis of highly

• substituted 1,2-dihydroisoquinolines 40 characterized by the presence of an α-hydroxy/alkoxy-α-carboxylate carbon pendant. The oxonium ylide 39 was prepared by a well-known procedure involving a rhodium carbenoid intermediate, generated in situ from the corresponding diazoacetate 37 under Rh2(OAc)4 catalysis

• , aldehydes and alkenes in a three-component reaction based on the cascade imine formation, azomethine ylide generation and [3 + 2] cycloaddition reaction for the synthesis of pyrrolidines. However, the adopted method to induce chirality in the final products is rather dissimilar. Thus, in 2006 Garner’s group

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• 4-nitrobenzoic acid, respectively. The substituent effects on the regioselectivity were also investigated. Keywords: 1,3-dipolar cycloaddition; azomethine ylide; regioselectivity; spirooxindole; Introduction Spirooxindoles are important synthetic targets due to their significant biological

• -unsaturated enones. Moreover, we envisioned that the additive might effectively tune the regioselectivity of a 1,3-dipolar cycloaddition of azomethine ylide. Herein, we report a three-component 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from isatin derivatives and benzylamine, with

• benzylideneacetone derivatives in the presence of various additives. It was found that the addition of water can significantly improve the regioselectivity and yield of this reaction [45][46][47][48]. More importantly, the regioselectivity of the 1,3-dipolar cycloaddition of azomethine ylide was reversed by the

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• precursors for organic synthesis, but also act as bioisosteres for enzyme inhibitors. Among various methods for their preparation, the carbonyl olefination with difluoromethylene phosphonium ylide represents one of the most straightforward methods. Results: The combination of (chlorodifluoromethyl

• . Conclusion: Similar to many other Wittig-type gem-difluoroolefination reactions in the presence of PPh3, the reaction of TMSCF2Cl with aldehydes and activated ketones is effective. Keywords: (chlorodifluoromethyl)trimethylsilane; difluorocarbene; gem-difluoroolefin; organo-fluorine; Wittig reaction; ylide

• difluoromethylene phosphonium ylide, which can be generated in situ either by the transformation of a difluorinated phosphonium salt or by the reaction between difluorocarbene (:CF2) and a phosphine (Scheme 1) [19][20][21][22][23][24][25][26]. In 1964, Fuqua and co-workers first reported the difluoromethylenation

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• indolones. Keywords: acrylamides; aroylacrylic acids; azomethine ylide; cyclative rearrangement; cycloaddition; multicomponent; spirooxindoles; Introduction The design of new spirocyclic compounds is intriguing due to their unique non-planar structure and great potential for binding to biomolecules due to

• 22.9° and the shortest distance between carbon atoms (C6…C15) is 3.04 Å). The mechanism of the azomethine ylide formation by a decarboxylative route has been repeatedly described by a number of authors and is depicted in Scheme 1 [35][36]. The reaction between isatin and the α-amino acid affords the

• azomethine ylide, which regioselectively adds to the C=C bond of acrylamide or aroylacrylic acid. Since the stereochemistry of the cycloadducts 4a and 6a was clarified by a single-crystal X-ray analysis, the structures of the reacting systems – the azomethine ylide and dipolarophiles (acrylamide and

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• Abstract The total synthesis of the endogenous inflammation resolving eicosanoid resolvin D2 (1) is described. The key steps involved a Wittig reaction between aldehyde 5 and the ylide derived from phosphonium salt 6 to give enyne 17 and condensation of the same ylide with aldehyde 7 to afford enyne 11

• using the common linchpin phosphorus ylide derived from phosphonium salt 6 [21][22] and each of the homochiral aldehydes 5 and 7 [9]. Synthesis of vinyl iodide 4 The synthesis of fragment 4 began with the production of the aldehyde 7 as shown in Scheme 2. A Wittig reaction between hemiacetal 8 [23] and

• the ylide derived from 9 provided the alkene 10 [9] with excellent stereoselectivity. Oxidation of 10 with Dess–Martin periodinane then afforded aldehyde 7. The phosphonium salt 6 [21][22] was produced from propargyl bromide via silylation of the derived sodium salt with TIPSCl followed by reaction

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones – First evidence for the 1,3-oxathiole–thiocarbonyl ylide interconversion

• Valerij A. Nikolaev,
• Alexey V. Ivanov,
• Ludmila L. Rodina and
• Grzegorz Mlostoń

Beilstein J. Org. Chem. 2013, 9, 2751–2761, doi:10.3762/bjoc.9.309

• react at room temperature with cycloaliphatic thioketones, e.g. 2,2,4,4-tetramethyl-3-thioxocyclobutanе-1-one and adamantanethione, via a cascade process in which the key step is a 1,5-electrocyclization of the intermediate thiocarbonyl ylide leading to tetrasubstituted spirocyclic 1,3-oxathioles. The

• temperature dependence of the main reaction product type obtained from dimethyl diazomalonate and 2,2,4,4-tetramethyl-3-thioxocyclobutanе-1-one as well as to verify reversibility of the thiocarbonyl ylide and 1,3-oxathiole interconversion, the calculations of the energy profile for the transformation of 1,3

• [1][2][3][4] and easily eliminates N2 forming the reactive thiocarbonyl ylide 6. This intermediate, after subsequent 1,5- or 1,3-electrocyclization produces 1,3-oxathioles 3,7 or thiiranes 5 and 8, respectively (Scheme 2, path A) [4][5][6][22]. In some instances, substituted thiiranes undergo

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• one-pot oxidation/Wittig procedure was implemented from 37a; treatment with the Dess–Martin periodinane [41] in the presence of the stabilised ylide afforded a 4:1 E:Z mixture of the product alkene 39a in good (74%) yield. A second purification by column chromatography isolated the E-alkene

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

• racemization could be overcome by performing the olefination with AlMe3–Zn–CH2I2 in benzene under non-basic conditions. While looking for non-racemizing conditions for the same reaction, Beaulieu et al. found that the ylide formed from methyltriphenylphosphonium bromide and n-BuLi in THF gave 62 in 69% ee, but

• in low yield (27%) [102]. With a different unstabilized ylide 65, the enantiopurity of the Wittig product increased to >95% ee. The erosion of enantiopurity was attributed to the ylide (Ph3P=CH2) being too basic. It is well known that phosphonium ylides form stable complexes with alkali metals during

• reversed to >10:1 favouring adduct 68 [105]. α,β-Unsaturated esters can be synthesized from stabilized ylides. Reaction of 1 with ylide 69 is E-selective. Depending on the solvent, the E/Z-ratio can vary from 3:1 (in MeOH) [106] to 100:0 (THF [107] or benzene [108]). Since stabilized ylides are less

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• the 4e− Pauli repulsion between the reactives in TSNPMdown compared to TSNPMup, and thus an increase of the activation barrier. Moreover, lower energy to deform the initial ylide (strain energy) is required in the latter TS. With that energetic diference, the computed ee is about 99%, in good

• unexpected regioselectivity of the 1,3-DC depicted in Scheme 6, calculations within the DFT framework were performed. In the accepted mechanism of the metal catalyzed 1,3-DC of azomethine ylides and acrylates, the α-carbon atom of the azomethine ylide (C2 in Figure 5) reacts with the β-carbon of the acrylate

• higher in the carbon in α-position to the carboxy group (C2). Initially, a model azomethine ylide derived from oxazolone 10 was considered (Figure 5). Moreover, an acyclic w-shaped ylide analogue (Ylide-II) was also studied as a reference. We chose this latter 1,3-dipole because it is known that with

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• cycloaddition is shown in Scheme 13. The reaction commences with oxidation of tetrahydroisoquinoline 41 to amine radical cation 48 by the photoexcited state of Ru2+. Subsequently, abstraction of a hydrogen atom α to the nitrogen atom of 48 yields iminium ion 49, which is then converted to azomethine ylide 50 by

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• variety of reactions e.g. cyclopropanation, X–H insertion, cycloaddition and ylide formation [13][15], and more recently, in the synthesis of valuable compound classes such as β-keto esters [16] and β-hydroxy-α-diazocarbonyl compounds [17], we aimed to develop an inherently safe continuous-flow EDA