Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• reaction with α-bromo ketoximes 1 (Scheme 36). The reaction requires a copper catalyst, which transforms the diazo compound 96 into a metal carbene complex 97. The latter reacts with a nitrosoalkene intermediate NSA (formed from α-bromo ketoxime 1) producing isoxazoline 93 with recovery of the catalyst

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

• Grzegorz Mlostoń,
• Paulina Pipiak,
• Róża Hamera-Fałdyga and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185

• applied [14]. Another approach, which opens access to diverse ethenes, is the ‘two-fold extrusion reaction’, which comprises the [3 + 2]-cycloaddition of a diazo compound with a thiocarbonyl dipolarophile and subsequent elimination of N2 followed by sulfur extrusion [15][16][17]. In our continuing studies

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• to maximize the formation of the diazo compound (Scheme 18) [87]. Starting from this initial investigation, Ley and co-workers developed an elegant application of this strategy for a sequential formation of up to three C–C bonds in sequence, by an iterative trapping of boronic acid species. The

• sequence starts with the reaction of diazo compound 20, generated under flow conditions, and boronic acid 19 (Scheme 19). Further sequential coupling with diazo compounds 21 and 22 led to boronates 23 or protodeboronated products 24 at the end of the sequence (Scheme 19). With the aim to exploit the

On the cause of low thermal stability of ethyl halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2016, 12, 1590–1597, doi:10.3762/bjoc.12.155

• bimolecular dimerization leading to azines; and 3) a reaction of the diazo compound with the solvent or a reactant prior to nitrogen extrusion. The fact that the decomposition rate of all halodiazoacetates showed first order kinetics and that t1/2 for 2b is independent of its concentration indicates that

• ) was included in the calculations even though the synthesis of this diazo compound has not been reported in the literature. We excluded 2c in our molecular modeling due to the need for a different basis set for iodine compared to the other halogens. We also included diethyl diazomalonate (2e, t1/2

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• prepare phosponylpyrazoles 217 in the presence of KOH in MeOH in 73–95% yields (Scheme 44) [82]. Based on their explanation, the treatment of dimethyldiazomethylphosphonate 213 with a nucleophilic base generates diazo compound 215. The subsequent [3 + 2] cycloaddition reaction of 215 with Knoevenagel

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• -cuparenone (8) through the construction of a five-membered ring prepared by an enantioselective carbenoid insertion into a C(sp3)–H bond (Scheme 3) [34]. To carry out the cyclization, the carbenoid was formed by the action of Rh2(OAc)4 on the diazo compound 6. That intermediate intramolecularly inserted into

• the interaction of the diazo compound 28 and the dirhodium complex 27. In sequence, the reaction proceeds through the transition state TS-30 to release N2, and yields the carbenoid 31. The divalent carbon attached to the rhodium atom starts to interact with the hydrogen of the C(sp3)–H bond of the

• )–H when X = Ph or H. The first reason concerns the relative stability of the carbenoids 38-Ph and 38-H. The first one, prepared from the donor/acceptor diazo compound 36-Ph, is 10.9 kcal more stable than the carbenoid 38-H obtained from the acceptor diazo compound 36-H. This observation was

Evidencing an inner-sphere mechanism for NHC-Au(I)-catalyzed carbene-transfer reactions from ethyl diazoacetate

• Manuel R. Fructos,
• Juan Urbano,
• M. Mar Díaz-Requejo and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2015, 11, 2254–2260, doi:10.3762/bjoc.11.245

• of a gold(I) source and a diazo compound. It was not until 2005 that the first example of this transformation was reported by our group [15][16], when the complex IPrAuCl (1) (IPr = 1,3-bis(diisopropylphenyl)imidazole-2-ylidene), in the presence of NaBArF4 (BArF4− = tetrakis(3,5-bis(trifluoromethyl

• two molecules of the diazo compound convert into an olefin and/or an azine (Scheme 4b), the second acting as a nucleophile attacking the metallocarbene intermediate [28]. However, our previous studies have shown that this gold-based catalytic system does not induce such non-desired carbene

• with the diazo compound and then evolution of nitrogen. However, that first step of substrate dissociation would be in disagreement with the observation of the enhancement of the reaction rate of nitrogen evolution when increasing the substrate:catalyst ratio, the dissociation of the substrate should

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• reaction with styrene, avoiding the use of hazardous diazo compound 7 [82]. Towards the end of 2013, a report by Olszewski, Skowerski and co-workers showed how a variety of commercially available catalysts (Figure 12) could be employed in air with nondegassed ACS grade green solvents. Their results were in

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

• successful procedure involving addition of Rh2(OAc)4 to a boiling 1:1.25 mixture of azirine 1a and diazo compound 2a in 1,2-dichloroethane (DCE) (procedure A) gave rise to oxazine 4a and azadiene Z-3a in 60 and 7% yields, respectively (Scheme 2, Table 1, entry 1). It was also shown that azadiene Z-3a did not

• -1,3-dienes with the C=C bond in Z-configuration have a sufficiently high activation barrier for cyclization and are usually stable up to 90–100 °C. Oxazine 4b was synthesized in a similar way from azirine 1b and diazo compound 2a (Table 1, entry 2), but in this case no traces of azadiene Z-3b were

• published procedure [25]. Diazo compound 2b slowly decomposes in the presence of Rh2(OAc)4 and 2,2-dimethyl-3-phenylazirine (1c) even at room temperature, but no conversion of the latter was observed according to 1H NMR spectroscopy. A satisfactory result was obtained, when the reaction was carried out at

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

• as well as oxazines 3a–c [10]. The corresponding ethyl 2-((E)-4-oxo-3-phenylpent-2-en-2-ylimino)acetate (E)-4j was not isolated from the reaction of azirine 5 with diazo compound 2b, probably due to its instability. Conclusion According to DFT calculations at the B3LYP/6-31G(d) level and experimental

• Cambridge Crystallographic Data Centre. Isoxazoles 1a [29], 1b [30], 1c–e [31], 1f,g [32] were prepared by the reported procedures. General procedure of reacting isoxazoles with diazo compounds. A long Schlenk tube containing a mixture of isoxazole (0.3–1.2 mmol) and diazo compound (1 equiv) in PhCF3 (1–2

• mL) was put into an oil bath preheated to 110 °C. To the vigorously stirred mixture, Rh2(OAc)4 (1–5 mol %) was added in one portion and stirred until N2 evolution has been stopped (10–15 min). An additional amount of diazo compound was added dropwise, and then the mixture was heated for an additional

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• analog that still exhibits similar inhibitory activity on hedgehog-signaling. For the sake of brevity of the overall synthetic sequence we defined carbacyclopamine analog 2 (see Figure 1) as our primary target. Results and Discussion A retrosynthetic analysis identified diazo compound 3 as a key

• was thought to establish the C-nor-D-homo steroid system, and a gold-catalyzed amination/annulation/aromatization sequence was planned to install the pyridine F-ring. Diazo compound 3 originates from diene 4 through standard transformations, the latter being accessible from commercially available and

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

• compound. Boiling an o-xylene solution of furanedione 1d and azirine 2a (1:1 ratio) gave bisadduct 18 in 34% yield (Scheme 6). This is less than when using the diazo compound as a source of acylketene, probably due to dimerization of ketene 6d under higher temperature. Compounds 3 and 17, stable at room

• . 4,5-Diphenylfuran-2,3-dione (1d) is the source of benzoylphenylketene 6d. Reaction of ketene 6d, generated from 2-diazo-1,3-diphenylpropane-1,3-dione, with azirine 2a was studied earlier [22]. Higher temperatures are needed to generate benzoylphenylketene 6d from furanedione 1d, than from the diazo

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

• formal [4 + 3] cycloaddition [82]. Starting from 4-methoxyphenol (90) Friedel–Crafts acylation and cyclization provided bicycle 91. Wittig olefination furnished benzofuran 92. Diazotransfer using p-ABSA yielded the crucial diazo compound 93, which was used in the following enantioselective

• -catalyzed cyclopropanation of silyl-enol-diazo compound 101 and Boc-protected pyrrole 147 resulted in the formation of intermediate cis-divinylcyclopropane 148, that rearranged under the reaction conditions to give the corresponding highly substituted bridged cycloheptadiene 149. Deprotection of the enolate

• coworkers [174] applied the DVCPR in the core structure synthesis of actinophyllic acid (218, see Scheme 25) [175]. Subjection of diazo compound 213 to copper catalysis yielded vinylcyclopropane 214. Deprotonation and silyl ether formation resulted in intermediate cis-divinylcyclopropane 215, which smoothly

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

• -dicarbonyl compounds with cycloaliphatic thioketones. The study was aimed at (i) the determination of the key directions of these processes in dependence of the type of diazo compound and (ii) the identification of their usefulness for the synthesis of sulfur-containing heterocycles and derived compounds

• formation of these compounds can be rationalized by pathways presented in Scheme 2 [4][22]. 1) Pathway A implies the initial 1,3-dipolar cycloaddition between the diazo compound 2 and the С=S bond of thioketone 1 giving rise to 1,3,4-thiadiazoline 10. The latter is usually an unstable intermediate species

• the thiocarbonyl ylide 6 is also possible via an alternative pathway C, that implies interaction of a dioxocarbene (formed after thermal decomposition of the diazo compound) with the sulfur atom of the C=S group [4][7][8]. The subsequent intramolecular 1,5-electrocyclization of the same intermediate 6

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

• cycloaddition, ylide formation, cyclopropanation and C–H insertion reactions [1][2][3]. A generally useful modification of diazo compounds is the substitution of the α-hydrogen for an electrophile. This substitution can be effected in the presence of a base or starting from the metalated diazo compound, and

• which the α-substituent on the carbene carbon varies (see below). The α-phenyl analogue of β-lactam 5b has previously been prepared by carbene C–H insertion. In these reports, the base-promoted decomposition of a hydrazone and subsequent thermolysis of the diazo compound in, e.g., toluene under reflux

4-Pyridylnitrene and 2-pyrazinylcarbene

• Curt Wentrup,
• Ales Reisinger and
• David Kvaskoff

Beilstein J. Org. Chem. 2013, 9, 754–760, doi:10.3762/bjoc.9.85

• liquid N2 at −196 °C, or at 2092 cm−1 upon isolation in an Ar matrix at 10 K. The diazo compound is also formed on matrix photolysis of the triazole (Figure 1). Compound 22 can exist as s-Z and s-E conformers. One conformer dominates, absorbing strongly at 2092 cm−1; the other, minor absorption is at

• 2076 cm−1 (Figure 1). Warming the neat diazo compound to ca. −30 °C causes ring closure to triazole 24. Compound 24 can be isolated in up to 20% yield in preparative pyrolysis of 23 [16]. Further FVT of either 23 or 24 at ≥450 °C/10−3 mbar results in the formation of approximately equal amounts of the

• ) or triazole 24 in an Ar matrix at 7–10 K causes efficient ring expansion to the cyclic seven-membered ring ketenimine 20 as observed by IR spectroscopy (Figure 2). In the case of triazole 24, efficient ring opening to the diazo compound 22 happens first (Figure 1), so the latter is the immediate

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

Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

• Farhan R. Bou-Hamdan,
• François Lévesque,
• Alexander G. O'Brien and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2011, 7, 1124–1129, doi:10.3762/bjoc.7.129

• expansion of 12, via 2H-azirine 3, affords didehydroazepine 4, which can be trapped by variety of nucleophiles to provide the corresponding azepine 5. Alternatively, intersystem crossing (ISC) of 12 gives rise to 32, which can dimerize to form diazo compound 6. Performing the reaction in the presence of

Gold-catalyzed naphthalene functionalization

• Pedro J. Pérez,
• M. Mar Díaz-Requejo and
• Iván Rivilla

Beilstein J. Org. Chem. 2011, 7, 653–657, doi:10.3762/bjoc.7.77

• a 1:1 mixture of IPrMCl (M = Cu, 1a; M = Au, 1b) and NaBAr'4, the diazo compound was consumed after 24 h at 60 °C (no significant reaction was observed at room temperature or at 40 °C). NMR analysis of the crude reaction product revealed that when 1a was used as the catalyst, only one compound was

• selectivity observed is similar to that reported by Müller's group with [Rh2(O2CC3F7)4] (60:22:18) [8]. However, in our case the yield of products (EDA-based) was quantitative: products derived from dimerization of the diazo compound, i.e., diethyl fumarate and maleate, were not detected. The absence of the

• % with respect to the diazo compound). Similarly to the previous results, the fused norcaradiene 3a (Scheme 5) was exclusively and quantitatively formed using the copper catalyst 1a, whilst the use of 1b afforded a mixture of three products in a 60:20:20 ratio. The major product was identified as the 3a

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

• the reaction of diazo compounds 1e and 1f with water, only 6-endo-dig cyclization products 2e and 2f were isolated as the sole product in yields of 69% and 75%, respectively. Functional groups such as bromo and hydroxy groups were tolerated under the present catalytic systems. When diazo compound 1g

• (R’ = H) was employed as the substrate, none of the cyclization product was detected and the water insertion product 4g was obtained in 81% yield. A tentative mechanism for this gold(I)-catalyzed cascade insertion/cyclization is proposed in Scheme 2. Decomposition of diazo compound 1 by (IPr)AuCl