Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• active electrophilic trap in the reaction mixture. 3-Diazoacetylacetone under Rh(II)-catalysis gives, along with a Rh(II) carbenoid, a highly electrophilic acetyl(methyl)ketene (12) via Wolff rearrangement (Scheme 3). The nucleophilic attack of the azirenooxazole 10j nitrogen on the ketene sp-carbon

• , entry 9). It is known that the Rh(II)-catalyzed reaction of 3-aryl-2H-azirines with ethyl diazoacetoacetate (2d) gives rise to 2H-1,4-oxazines as a single product [15]. The absence of products like 6 or 7 may be caused by a decreased propensity of the carbenoid derived from 2d to undergo a Wolff

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

• -electrocyclization to give oxazine E (Scheme 1). At the same time, the third mechanism of the reaction, involving a one-step formation of 1-oxa-5-azahexa-1,3,5-triene D, cannot be excluded. The reaction of a carbenoid with isoxazoles is the only known one-step intermolecular reaction which can in principle produce

• and kinetic stabilities of isoxazolium N-ylides, probable intermediates in a carbenoid- or carbene-mediated one-atom isoxazole ring expansion. Preliminary calculations at the DFT B3LYP/6-31G(d) level with the PCM solvation model for dichloromethane were performed for the model reaction of isoxazoles A

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

• ). Azetidinone 72 was then formed through a rhodium-catalyzed intramolecular carbenoid insertion into the N–H bond as the first pivotal step of the synthesis. The next key step was to introduce the exocyclic double bond with control of the stereochemistry of the double bond. For that purpose, a variety of

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

• 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

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

• the solvent at ≥100 °C through an initial chlorine particle transfer to give a Cl,K-carbenoid. This short-lived intermediate disclosed its occurrence through a reversible proton transfer which competed with an oxygen transfer from DMSO that created dimethyl sulfide. The presumably resultant transitory

• afforded 1,1,3,3-tetramethylindan-2,2-dicarboxylic acid. Brominative deoxygenation of the ketones furnished two one-sidedly overcrowded bromoalkenes. Some presently relevant properties of the above Cl,K-carbenoid are provided in Supporting Information File 1. Keywords: brominative deoxygenation; carbenoid

• groups. Instead, the substitution products 7 were obtained from 6 in THF via the cyclic Li,Cl-carbenoid 8 at room temperature (rt) by the carbenoid chain mechanism [3], as indicated in the bottom line of Scheme 1. These SNV reactions proceed properly because 8 has a reduced (albeit not vanishing

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

• alkynyl substituted α-diazo ketones. Transition metal-catalyzed diazo-decomposition of compound 240 (see Scheme 30) resulted in the formation of metallacyclobutene 241, followed by rapid metallacycloreversion to give carbenoid species 242. Intramolecular cyclopropanation furnished divinylcyclopropane 243

• give intermediate vinyl-allenecyclopropane 249, followed by a DVCPR to furnish cycloheptadiene 250. 1,2-Shift and vinyl-carbenoid formation sequences Two major pathways to generate divinylcyclopropanes using transition metal catalysis have been developed. Uemura and coworkers [204] were the first to

• apply the transition metal catalyzed 1,2-acyl shift with subsequent vinyl carbenoid formation. Propargylic acetate 251 (see Scheme 33) has been shown to undergo 5-exo-dig cyclization via 252 to give zwitterionic intermediate 253. A concomitant fragmentation reaction yielded vinyl-carbenoid 254. Uemura

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

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• a nucleophilic intramolecular attack of the carboxy moiety on the activated alkyne. 1,2-Migration of the ester affording a gold–carbene of type A is usually preferred when a terminal alkyne is used [38][39][40]. Based on this concept, several groups have shown that the resulting carbenoid

• bisgold complex suggests that only one Au–Cl bond remains intact in the gold catalyst (Scheme 16). From a mechanistic point of view, the authors proposed that the intermediate species can be viewed as either a cyclopropylgold carbenoid XII or as a zwitterionic alkenylgold derivative XII’, the latter being

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• represented as two resonance structures highlighting both the carbocation or carbenoid nature of this intermediate (Scheme 2). Results and Discussion As established in Scheme 2, we were intrigued by the possibility that o-(alkynyl)-(3-methylbut-2-enyl)benzenes 1 could undergo a 6-endo-dig cyclization in the

• the allylic position. To account for the stereoselectivity of these reactions we proposed the generation of a stabilized gold–carbenoid intermediate such as A that undergoes stereoselective attack by water (Scheme 6). Furthermore, we have also carried out the methoxycyclization of selected 1,6-enynes

• -exo cyclization could not be separated in the case of 6a and 6h. Finally, to support the proposed intermediacy of gold–carbenoid intermediate 4 or 4’ (Scheme 4), we treated enyne 1b with D2O instead of water and under the same catalytic conditions we observed the exclusive formation of the deuterated

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• enantiomer. With eleven synthetic operations and a longest linear sequence of only seven steps, this route is highly convergent and employs a novel Rh-carbenoid-mediated formation of 30 as its key step. The synthesis of the natural enantiomer of (+)-K252a [(+)-27] was carried out in an analogous fashion

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

• Marie Hoffmann,
• Solène Miaskiewicz,
• Jean-Marc Weibel,
• Patrick Pale and
• Aurélien Blanc

Beilstein J. Org. Chem. 2013, 9, 1774–1780, doi:10.3762/bjoc.9.206

• ]. Intermediate B, which could also be generated by carbophilic gold activation followed by nucleophilic addition of the acyloxy part, could evolve into the gold carbenoid species D [31]. Intermediate C, possessing the correct stereochemistry, and D might then cyclize by an attack of the carbonyl function on the

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• reflux: a reaction that plausibly occurs with a free halocarbonylcarbene or a mercury carbenoid as intermediate [45][55][56]. In the case of the α-bromo-β-lactam 5b, the authors reported an exo-diastereoselectivity of 5.25:1. In order to compare the reactivity of other halides in the α-position, we

• surprisingly low yield obtained may be due to decomposition during the chromatographic step, as indicated by a change in colour from red to purple, possibly owing to the formation of I2. In a broader context, related examples of carbene/carbenoid C–H insertions to form β-lactams exist in the literature, in

• correlation between the electron-donating ability of the dirhodium(II) catalyst and the obtained yield of the β-lactam 5d (see Table 5.2 in Supporting Information File 1). In our hands, the more stabilised carbenoid afforded the best result, suggesting that the intramolecular C–H insertion reaction was

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• phenoxyl radical with PbO2 in toluene [36]. Synthesis from diazomethylenebisphosphonates The feasibility of synthesizing trisphosphonate esters under mild conditions via metal-carbenoid-mediated P–H insertion reactions was demonstrated by Gross et al. [25]. In particular, the reaction between tetraethyl

• quinone methides 17 and 19. Unexpected phosphonylation of the aromatic nucleus in reactions of quinone methides 19 and 21. Multistep synthesis of trisphosphonate 18 starting from quinone methide 25. Synthesis of hexaethyl methylidynetrisphosphonate (6) via metal-carbenoid-mediated P–H insertion reaction

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• 1,4-addition/carbozincation of dialkylzincs or alkyl iodides based on zinc atom radical transfer, in the presence of dimethylzinc with β-(propargyloxy)enoates having pendant iodo- and bromoalkynes, is disclosed. Formation of the carbenoid intermediate is fully stereoselective at −30 °C and arises from

• a formal anti-selective carbozincation reaction. Upon warming, the zinc carbenoid is stereochemically labile and isomerizes to its more stable form. Keywords: carbenoids; carbometallation; carbozincation; radicals; tandem reaction; Introduction The last few years have witnessed a gaining interest

• intermediate formation of an alkylidene zinc carbenoid as deuterated 4aa-D was produced (Table 1, entry 2). As previously noted in the case of similar 1,4-addition/carbozincation sequences [37][38], deuterium incorporation was nearly quantitative for the Z isomer, and much lower for the E one. More

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

• 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

• diastereomers (the NCHR epimers) in approximately equal ratio [18]. The DMAD adduct 19 was also formed as a 2:1 mixture of two diastereomers; unfortunately, the highly viscous oil obtained could not be purified completely. Rhodium-catalysed carbenoid reactions of other mercapto-functionalised diazoesters With

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

• carbenoid tethered to an imine group (Scheme 10). A subsequent attack of this imine to the carbenoid generates the reactive azomethine ylide intermediate XIV, which undergoes a (3 + 2) dipolar cycloaddition with an intramolecularly tethered alkene or alkyne. Thus, interesting azabicyclo[3.2.1]octane

• carboxyl unit on the metal-activated alkyne complex XXI. When a terminal alkyne is used (Figure 1, R = H), the 1,2-migration of the acetate moiety is preferred, affording an alkenyl–gold carbenoid species of type XXIII. In contrast, internal alkynes typically experience a 1,3-acyloxy migration rendering

• propargylic benzoates with α,β-unsaturated imines to give azepine products 35 with excellent yields [77]. The formal (4 + 3) cycloaddition takes place in three basic stages: 1) Generation of the gold carbenoid by a 1,2-acyloxy migration, 2) attack of the imine on these electrophilic species to give an allyl

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

• examples of sp3 C–H bond insertion via a cationic gold(I)–carbenoid intermediate. 4.3 Cycloadditions Intramolecular [M + N]-type cycloaddition reactions are powerful tools for accessing complex molecular frameworks [98]. Several gold-catalyzed [3 + 2] [99], [4 + 2] [100][101][102][103][104][105], and [4

• triggered a new reaction mode of furan–yne cyclization and delivered a new class of tetracyclic system 263 rather than a phenol (Scheme 46) [141]. Insertion of a C–H bond into a metal–carbenoid is a highly useful method for forming a new carbon–carbon bond. An atypical gold–carbenoid induced cleavage of a

• sp3-hybridized C–H bond can be achieved by undergoing 1,3-addition to a vinyl–carbenoid intermediate [142]. The bicyclo[3.2.1]oct-6-en-2-ones 265 and 267 could be synthesized stereoselectively by this method. Deuterium labeling experiments indicated the cyclization involved an unprecedented 1,3

When gold can do what iodine cannot do: A critical comparison

• Sara Hummel and
• Stefan F. Kirsch

Beilstein J. Org. Chem. 2011, 7, 847–859, doi:10.3762/bjoc.7.97

• presence of electrophilic iodine. The reader will also realize how gold-catalyzed processes, which mechanistically benefit from the carbenoid character [55][56][57][58] of the reactive intermediates, cannot be matched by electrophilic processes. As highlighted in the discussion, a starting substrate can be

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

• 10.3762/bjoc.7.90 Abstract Efforts to trap early intermediates of the gold-catalyzed phenol synthesis failed. Neither inter- nor intramolecularly offered vinyl groups, ketones or alcohols were able to intercept the gold carbenoid species. This indicates that the competing steps of the gold-catalyzed

• ][24][25]. Moreover, interesting new pathways were opened when ynamides and alkynyl ether substrates were employed: Here A is also a possible intermediate along these pathways [25]. Since direct experimental evidence existed only for C and D, we intended to intercept the postulated carbenoid

• Intermolecular olefinic trapping reagents We started with the simplest experiments, namely the intermolecular trapping of the gold carbenoid intermediates. When 3 was reacted in the presence of an activated olefin, such as norbornene or styrene, phenol 4 was formed exclusively in essentially quantitative yield

Solvent- and ligand-induced switch of selectivity in gold(I)-catalyzed tandem reactions of 3-propargylindoles

• Estela Álvarez,
• Delia Miguel,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez,
• Félix Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 786–793, doi:10.3762/bjoc.7.89

• esters have been extensively investigated. In these processes the gold-carbenoid species generated are able to undergo a wide variety of further transformations [8][9][10][11]. In addition, propargylic sulfides have also been reported as useful substrates for this type of process, participating in

• reactions of propargylic systems. Thus, 3-propargylindoles 1 give rise to α,β-unsaturated gold-carbenoid intermediates 2 that evolve through different pathways depending on the substituents at the propargylic and terminal positions of the alkyne moiety (Scheme 1). If (hetero)aromatic substituents are

• setting of the reaction conditions (modulation of the electronic properties of the ligands, counter ion, solvent, substitution pattern of the substrates, etc.). Herein, we report our efforts to control the two competing pathways in the evolution of gold-carbenoid intermediates generated by an initial 1,2

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

• , intermediates characterize these competitive processes, i.e., 1,2-migration via metal "carbenoid" 81 formation and [3,3]-sigmatropic rearrangement via allenyl acetate 82 as an intermediate (Scheme 24) [5][56][57]. In 2008, Toste and co-workers reported a gold(I)-catalyzed cycloisomerization of cis-pivaloyloxy

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

• undergo subsequent ring-opening to produce an organogold species that can be viewed as a hybrid between a gold-stabilized allylic carbocation B and a gold carbene C. The organogold carbenoid species generated by the ring-opening of cyclopropenes can participate in a variety of reaction types such as

• ) carbenoid complexes, Toste et al. highlighted the importance of the substitution pattern and the ligands (Scheme 4). Interestingly, DFT calculations were carried out for organogold species that can actually be generated by ring-opening of cyclopropenes, and therefore the authors examined experimentally the

• reflux [33][38]. These reactions appear to constitute the first examples of intramolecular olefin cyclopropanation promoted by a silver carbenoid generated by ring-opening of a cyclopropene. We envisioned that the gold carbene resulting from the ring-opening of appropriately substituted cyclopropenes

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

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

• insertion The laboratory of G.A. Sulikowski proposed a synthesis of 1,2-aziridinomitosenes [106][107] using as key transformations a Buchwald–Hartwig cross-coupling [108][109][110] and a chemoselective intramolecular carbon-hydrogen metal-carbenoid insertion reaction (Scheme 39). The chiral pyrolidine 136

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

• carbenoid-based reagents. Introduction Allenylsilanes are versatile intermediates for organic synthesis.[1][2] They have two main modes of reactivity: firstly, as propargyl anion equivalents in thermal [3][4] or Lewis acid-mediated [5][6] addition to carbonyls, acetals and imines, and secondly as three

• problem, it gave us the encouragement to screen other titanium carbenoid-based methylenating reagents. The Petasis reagent (dimethyltitanocene) [31][32] was our next choice, and we were pleased to find that it afforded modest to excellent yields of the allenylsilanes in reaction with most of the ketene