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

• structures, see Figure 16) were inert to the ylide 21 [49]. When we combined the pregenerated iminium salts 3a–e with the sulfur ylide 21, the expected cyclopropanes 23 were indeed formed in good yield, although with low diastereo- and enantioselectivity (Figure 14) [64]. Even the rate constants calculated

• by Equation 1 agreed, within the general tolerance, with the experimental values; with one exception. The iminium intermediate derived from indole-2-carboxylic acid (3g) reacted at least 105 times faster with the sulfur ylide 21 than calculated by Equation 1, which can be explained by electrostatic

• activation as initially proposed by MacMillan (Figure 15) [49]. Thus, the failure of the imidazolidinones 1a and 1b to catalyze cyclopropanations with the sulfur ylide 21 is not due to the low reactivities of sulfur ylides toward iminium ions, but is due to the high Brønsted basicity of the sulfur ylides 24

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• explanation is the formation of azomethine ylide intermediate 11 (Scheme 8) [19][20]. The carbanion of ylide 11 is then protonated by benzoic acid, and the resulting benzoate anion supports the aromatization process. In fact, Seidel and co-workers provided the experimental evidence for the existence of

• azomethine ylide intermediates in the Tunge pyrrole formation and in the formation of N-alkylindoles from indoline [19]. These reactions are considered C–H activation reactions, as during the azomethine ylide formation, the C–H bond that is cleaved is not activated by electron-withdrawing (such as ester

• indicated that the formation of acetic acid assisted azomethine ylide 13 is the most plausible pathway for the rearrangement process [21]. The first step is the nucleophilic addition of an amine to the carbonyl group to generate a carbinolamine intermediate (Scheme 8). It then becomes O-acetylated by acetic

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• 3a (Table 1, entry 6). The allylic phosphorus ylide species can be recognized in spectra c from the combination of 2d and TP (1:1) (Figure 2, also see Figure SI-1 in the Supporting Information File 1) [59]. As reported before [15][51], TP attacks MBH carbonate to afford allylic phosphorus ylide I

• , which attacked the maleimide to produce intermediate II (Scheme 2). Since there is a steric effect between the phenyl group and the benzyl group in intermediate II-B, allylic phosphorus ylide I using its Si-face to attack maleimide is favored (intermediate II-A). Undergoing Michael addition and

• wasting maleimide and catalyst (spectra d in Figure 2). Hypothetically, the activity of the in situ generated allylic phosphorous ylide I is crucial for the yield of product. If the activity of phosphorous ylide is not high enough, it may deprotonate the NH proton in TP, which will cause the catalyst to

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• regiospecifically manipulated through diazotransfer to form diazoimide 11 [27]. Rhodium(II)-catalyzed cyclization of 11 between modules 1 and 2 could generate a carbonium ylide intermediate 12. In this system, there is a dynamic conformational equilibrium of the tertiary amide, which is expected to allow divergent

• group in 73% yield (two steps). Cyclization of 24 and subsequent cycloaddition between the resulting carbonium ylide and the indole C2–C3 double bond efficiently proceeded by the treatment with 5 mol % Rh2(OAc)4 catalyst in benzene under reflux to afford hexacyclic scaffold 25 in 78% yield. The cyclized

• (Scheme 3). According to the previously reported protocol [22], Ugi reaction employing allylamine (31) and stepwise installation of a diazoimide group provided 35 in good yield. Upon treatment of 35 with Rh2(OAc)4 in benzene under reflux, 1,3-dipolar cycloaddition of the ylide intermediate with the

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• three steps. Upon rhodium-catalysed dediazoniation, two intramolecular carbenoid reactions competed, namely the formation of a cyclic sulfonium ylide and that of a six-ring carbonyl ylide. The S-methyl and S-benzyl ylides 12a and b could be isolated, while S-allyl ylide 12c underwent a [2,3]-sigmatropic

• -β-ketoesters 1, stable four- to seven-membered cyclic ylides 2 were obtained (Scheme 1); in the case of R2 = allyl, however, the ylides underwent a spontaneous [2,3]-sigmatropic rearrangement. On the other hand, the conversion of methionine-derived diazoketone 3 into the cyclic sulfonium ylide 4 was

• not accomplished through the carbenoid route, but rather by cyclisation of a diazonium ion followed by deprotonation of the resulting sulfonium ion (Scheme 2) [17]. A diazoketone such as 3 has the structural prerequisites to undergo two types of intramolecular carbenoid ylide-forming reactions

Synthesis of fused tricyclic amines unsubstituted at the ring-junction positions by a cascade condensation, cyclization, cycloaddition then decarbonylation strategy

• Iain Coldham,
• Adam J. M. Burrell,
• Hélène D. S. Guerrand,
• Luke Watson,
• Nathaniel G. Martin and
• Niall Oram

Beilstein J. Org. Chem. 2012, 8, 107–111, doi:10.3762/bjoc.8.11

• sequence involving condensation to an intermediate imine, then cyclization and formation of an intermediate azomethine ylide and then intramolecular dipolar cycloaddition. The fused tricyclic products are formed with complete or very high stereochemical control. The hydroxymethyl group was converted into

• an aldehyde – which could be removed to give the tricyclic amine products that are unsubstituted at the ring junction positions – or was converted into an alkene, which allowed the formation of the core ring system of the alkaloids scandine and meloscine. Keywords: alkaloid; azomethine ylide

• transformation [2][3][4][5][6][7][8]. We have been studying the intramolecular dipolar cycloaddition of azomethine ylides in synthesis [9][10][11][12][13][14][15][16] and were able to show that the azomethine ylide could be prepared in situ by a cyclization step [17][18]; for example, by heating the aldehyde 1

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

• type 1 and alkynes (Scheme 1) [24][25]. The mechanism proposed by the authors involves an initial 5-endo nucleophilic attack of the carbonyl moiety on the metal–alkyne complex to generate a carbonyl ylide intermediate I, which undergoes a regioselective (4 + 2) cycloaddition with the external alkyne. A

• aforementioned mechanistic pathway [26]. According to the theoretical data, the formal (4 + 2) cycloaddition would indeed comprise a two-step process consisting of a dipolar (3 + 2) cycloaddition of the carbonyl ylide I to afford a carbene species III [27][28], followed by a 1,2-alkyl migration to yield the

• enantioselective examples of these type of cycloadditions promoted by a chiral cationic platinum–diphosphine catalyst [38]. In contrast to these examples that proceed through an initial endo-dig cyclization and generate gold–carbonyl ylide species, the group of Liu recently demonstrated that it is also possible to

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

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

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• synthesis of the endo-pyrrolidine core of 5 is the key step for the preparation of these antiviral agents, and can be efficiently achieved by a 1,3-dipolar cycloaddition (1,3-DC) between the corresponding azomethine ylide and an alkyl acrylate [14][15][16][17][18] (Scheme 1). The first synthesis of racemic

• product 1, and other derivatives including compounds 2, was achieved in several steps using, as the key reaction, the silver(I) or lithium(I)-metalloazomethine ylide, under basic conditions, and tert-butyl acrylate. The enantiomeric samples were isolated by semi-preparative chiral HPLC [9][10]. The first

• of the 1,3-DC employing chiral metallic Lewis bases arises from the blockage of one of the prochiral faces [40]. In this way, our results (in terms of DFT calculations) show that there is only one energetically accessible conformation due to the high substitution of the leucine-derived ylide (Figure

Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

• Paul W. Davies,
• Nicolas Martin and
• Neil Spencer

Beilstein J. Org. Chem. 2011, 7, 839–846, doi:10.3762/bjoc.7.96

• (Scheme 4). Reduction using lithium aluminium deuteride led to the insertion of the label at the benzylic position. Oxidation to the aldehyde followed by condensation with tosylamide afforded the deuterated imine 6. Aziridination using the sulfonium ylide generated in situ from 7 proceeded smoothly to

High chemoselectivity in the phenol synthesis

• Matthias Rudolph,
• Melissa Q. McCreery,
• Wolfgang Frey and
• A. Stephen K. Hashmi

Beilstein J. Org. Chem. 2011, 7, 794–801, doi:10.3762/bjoc.7.90

• intermediates A or B. Apart from intermolecular trapping [26][27][28][29][30][31][32][33], intramolecular trapping of such carbenoids has also been reported [34]. One option would be to offer a competing carbonyl group, to produce a carbonyl ylide, which could then undergo a 1,3-dipolar cycloaddition [35]. The

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

• formation of the 1,4-furan dipole (Scheme 21). In fact, a resonance structure of 60 can be envisaged entailing a gold–carbene and a carbonyl ylide 63. Upon 1,3-dipolar cycloaddition with the alkoxy vinyl ether, bridged bicycle 64 is formed. 1,2-Alkyl migration and bridge opening produces a spiro cation 66

Intraannular photoreactions in pseudo-geminally substituted [2.2]paracyclophanes

• Henning Hopf,
• Vitaly Raev and
• Peter G. Jones

Beilstein J. Org. Chem. 2011, 7, 658–667, doi:10.3762/bjoc.7.78

• with the ylide prepared from cyclopropylcarbinyl triphenylphosphonium bromide and obtained in quantitative yield a product mixture consisting of the three possible diastereomers E,E-, E,Z- and Z,Z-22 (Scheme 8), the latter being the main product as is often observed in classical Wittig reactions

Sequential Au(I)-catalyzed reaction of water with o-acetylenyl-substituted phenyldiazoacetates

• Lei Zhou,
• Yizhou Liu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2011, 7, 631–637, doi:10.3762/bjoc.7.74

• steps. Keywords: alkyne; carbene O–H insertion; cyclization; diazo compounds; gold catalysis; 1H-isochromene; Introduction Transition metal carbene complexes are versatile intermediates and can undergo diverse transformations, including X–H (X = C, O, S, N, etc.) insertions, cyclopropanations, ylide

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• %. This step could potentially be improved by using different reaction conditions or an excess of the ylide. The hydrogenation of the corresponding olefins is straightforward and proceeds in high yield. In the case where a Pd-sensitive group is present, such as a chlorine substituent in 6e, modification

Miniemulsion polymerization as a versatile tool for the synthesis of functionalized polymers

• Daniel Crespy and
• Katharina Landfester

Beilstein J. Org. Chem. 2010, 6, 1132–1148, doi:10.3762/bjoc.6.130

• polymerized via various heterophase polymerizations, including polymerization in miniemulsion. The first report on polymerization of ethylene in miniemulsion describes the synthesis of polyethylene nanoparticles in the presence of a nickel–ylide complex [10]. The catalyst was dissolved in toluene and

• ethylene and up to 3 mol % 1-butene. Small nanoparticles (~200 nm) could be obtained by ethylene polymerization with a nickel(II) keto–ylide complex with 10% solids content in direct miniemulsion [63]. The same group copolymerized ethylene and polar and non-polar α-olefins in miniemulsion with a P,O

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

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

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• used in the total synthesis of mucocin (Scheme 21) [65]. The ylide 149, which was synthesized from the cis-THF alcohol 148a, was coupled with the butenolide aldehyde 150 via a Wittig reaction to afford the THF aldehyde 151 after further 3 steps. Then addition of the magnesium derivative of iodide 152

• Swern oxidation, and then reaction of the resulting aldehyde with CH3(CH2)13MgCl gave the bis-THF segment 250. The coupling reaction between the aldehyde prepared from 250 and the ylide prepared from 47 gave the enyne 251, which was hydrogenated. Global deprotection allowed completion of the synthesis

Expedient syntheses of the N-heterocyclic carbene precursor imidazolium salts IPr·HCl, IMes·HCl and IXy·HCl

• Lukas Hintermann

Beilstein J. Org. Chem. 2007, 3, No. 22, doi:10.1186/1860-5397-3-22

• can be induced by chloromethylethers. Loss of HCl from B (presumably to A, which is a monobasic species)[13] gives an imino-azomethin-ylide 1,5-dipole C (only one mesomeric structure shown), which will undergo 1,5-dipolar cyclization (6π electrocyclization) [18][19][20] to an oxy-imidazoline D

Synthesis of highly substituted allenylsilanes by alkylidenation of silylketenes

• Stephen P. Marsden and
• Pascal C. Ducept

Beilstein J. Org. Chem. 2005, 1, No. 5, doi:10.1186/1860-5397-1-5

• )ketenes were used as substrates.[16][17] Thus, only 3-substituted and 3,3-disubstituted allenylsilanes have thus far been accessed by alkylidenation of silylketenes, whilst no reports of the successful introduction of non-stabilised ylide equivalents have been forthcoming. A second impediment to the

• yield, Scheme 2, Table 2. As expected, reactions with the more substituted ylide 4 were significantly slower than those with the parent ylide 5 (compare reaction temperatures and times, entries 1, 3 and 5 versus entries 2, 4 and 6). Increasing the steric bulk of the ketene substituent also slows the

Reagent controlled addition of chiral sulfur ylides to chiral aldehydes

• Varinder K. Aggarwal and
• Jie Bi

Beilstein J. Org. Chem. 2005, 1, No. 4, doi:10.1186/1860-5397-1-4

• transformations.[1] Indeed, near perfect levels of asymmetric induction with high diastereocontrol have been achieved with aromatic aldehydes (Scheme 1). In such reactions, the C1 stereochemistry is controlled by ylide conformation, face selectivity, and the degree of reversibility in formation of the anti

• clearly shown by sulfide 2 could be exploited in reactions with chiral aldehydes and to what extent it might dominate over substrate control (Scheme 2).[3] Again C1 stereochemistry should be controlled by ylide conformation, face selectivity, degree of reversibility in anti betaine formation, and is not

• (dimethylamino)-phosphoranylidene]-phosphoric triamide ethylimine,) [4][5] (sulfur ylide 4) was initially investigated to establish the degree of substrate control. This furnished a mixture of 3 epoxides 7a, 7b, and 7c in a 37:14:49 ratio (Table 1, entry 1). The cis and trans isomers are easily distinguished by