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

• briefly studied the thermal, non-catalytic cyclopropanation of styrenes and compared the results to the analogous Rh(II)-catalyzed reactions. Keywords: carbenes; catalysis; cyclopropanation; halo diazoacetates; half-lives; thermal stability; Introduction The chemistry of diazo compounds has fascinated

• halodiazoacetates 2a–c (Scheme 1) from 1 and studied their reactivity in Rh(II)-catalyzed reactions [11]. In the presence of Rh(II) catalysts the halodiazoacetates extrude N2 and form the corresponding Rh–carbenes which undergo typical carbenoid reactions such as cyclopropanation [11], cyclopropanation–ring

• investigated the reactivity of the carbenes generated thermally at ambient temperature in a non-catalytic fashion. As a probe, we elected the standard cyclopropanation reaction of styrenes. We found that the presence of styrene and/or methyl 4-nitrobenzoate (internal standard) did not change the rate of the

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

• carbenoid insertion into the C(sp3)–H bond (63) and the other as a result of the cyclopropanation reaction (64, Table 9). Both examples reported by Suematsu and Katsuki showed very good yields and excellent enantiomeric excesses of the products. This work is noteworthy because it is the first report in the

• metathesis (RCM) [68]. The insertion of the rhodium carbenoids derived from vinyl diazoacetate into the C(sp3)–H bonds of the alkenylcarbamates 97a–d yields two reaction products (Table 10). The major one (99a–d) was the result of the cyclopropanation reaction of the double bond present in 97a–d. The minor

• cyclopropanation product was also observed in 14% yield. Ethylbenzene (110) was used and also showed high regioselectivity favoring the carbenoid insertion into benzylic C(sp3)–H bonds (Scheme 24). The diastereoisomers 111 and 112 were obtained in 45% yield and 16%, respectively, and moderate stereoselectivity was

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• then turn to asymmetric 1,2-additions followed by conjugate additions, a cyclopropanation, (ep)oxidations, α-functionalisation processes, cycloadditions, domino processes and finally miscellaneous reactions. We ultimately aim to demonstrate through this plethora of diverse processes, that the 6’-OH

• cyclopropanation using dimethyl bromomalonate (57) and some form of Michael acceptor. In this process, the enolate resulting from the initital conjugate addition attacks the C–Br bond to form a three-membered ring. In our work in this area, we designed a new cupreine derived catalyst HCPN-59 to add dimethyl

• review are already domino reactions (e.g., MBH, and the cyclopropanation), a recent and clearer example of the use of a 6’-OH cinchona derived catalyst in such a process comes from the laboratory of Samanta and co-workers [67][68]. They have demonstrated an enantioselective domino reaction between 3

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

• functionalization; olefin cyclopropanation; Introduction The discovery of the catalytic capabilities of soluble gold(I) species toward the hydration of alkynes by Teles and co-workers [1] is considered as the rising of the golden era for the use of this metal in homogeneous catalysis [2][3]. A number of

• reaction (olefin cyclopropanation). (b) Side-reactions of carbene or diazo coupling commonly observed. The outer- and inner-sphere routes for this transformation. Acknowledgements Support for this work was provided by the MINECO (CTQ2014-52769-C3-1-R), and the Junta de Andalucía (P10-FQM-06292).

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

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

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• halodiazoacetates. The formation of the quinoline structure is probably the result of a cyclopropanation at the 2- and 3-positions of the indole followed by ring-opening of the cyclopropane and elimination of H–X. Keywords: catalysis; cyclopropanation; indole; quinoline; Rh(II); ring expansion; Introduction The

• usually directed to the C2-position [5][6][7][8]. Electron-withdrawing groups (acyl, carbamoyl) at the indole nitrogen typically lead to cyclopropanation products that can be purified and isolated. Several reaction pathways have been proposed to account for the observed reactivity, but the mechanism for

• many of the reactions between indoles and metal-bound carbenes are unclear [5][6][7][8]. We have for some time worked with halodiazoacetates and studied their reactivity in cyclopropanation reactions [17], C–H insertion and Si–H insertion reactions [18]. Halodiazoacetates can be made quantiatively and

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• carbocation (Scheme 3) [34][35][36][37][38][39][40]. Intramolecular cyclopropanation reactions are often characterized by prolonged treatment with an acid [41][42][43][44][45][46]. Stabilization of the intermediate carbocation by the lone pair of the oxygen atom is enabled by lone-pair conjugation (O-lp

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs)

• Malgorzata Adamkiewicz,
• David O’Hagan and
• Georg Hähner

Beilstein J. Org. Chem. 2014, 10, 2897–2902, doi:10.3762/bjoc.10.307

• %, with a slightly lower conversion rate in case of F, which might be due to its higher electronegativity and an associated higher repulsion between the terminal groups after cyclopropanation. Conversion rates were determined by correcting the experimental C3/(C1 + C2) ratios from Table 1 with a factor of

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

• summarized, as well as an overview of the synthesis of the employed phosphonamide reagents. Keywords: conjugate addition; cyclopropanation; olefination; organophosphorus; phosphonamide; total synthesis; Introduction Chiral non-racemic and achiral cyclic phosphonamide reagents 1–7 (Figure 1) have been

• used for limited exploratory studies. Cyclopropanation and aziridination The cyclopropanation of α,β-unsaturated esters and lactones using chiral phosphonamide reagents is a special case of the conjugate addition–enolate alkylation sequence. The application of chloroallyl phosphonamides such as (trans

• cyclopropane 50a. Starting with (cis,R,R)-47b, the isomeric exo,endo product 50b is obtained as major isomer. The cyclopropanation reaction tolerates a wide range of Michael acceptor subtrates such as enones, lactones, lactams, and acyclic α,β-unsaturated esters. The obtained products can easily be cleaved to

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• , compound 1 was subjected to carbonyl reduction which occurred with high stereoselectivity from the less hindered, convex side of the bicyclic system, resulting in alcohol 2 along with traces of its epimer. To increase the stereoselectivity of the upcoming cyclopropanation reaction it seemed appropriate to

• protect the secondary hydroxy group as TBS ether (→ 3). Indeed cyclopropanation of 3 with diethylzinc and CH2I2 proceeded stereospecifically, again from the convex side of the bicyclic system, to give 4. Subsequent nucleosidation of 4 via the Vorbrüggen procedure [31][32] with transient protection of the

Synthesis of chiral N-phosphoryl aziridines through enantioselective aziridination of alkenes with phosphoryl azide via Co(II)-based metalloradical catalysis

• Jingran Tao,
• Li-Mei Jin and
• X. Peter Zhang

Beilstein J. Org. Chem. 2014, 10, 1282–1289, doi:10.3762/bjoc.10.129

• poor yield (Table 1, entry 8). To our delight, the use of catalyst [Co(P5)] (P5 = 3,5-DitBu-QingPhyrin), which was shown to be effective in asymmetric intramolecular olefin cyclopropanation [37], led to significant further improvement in enantioselectivity to 81% ee although the yield for the

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• rotation around the C3–C4 bond present in the azetidine derivative Ia by incorporating an appropriate spiro moiety. The cyclopropyl moiety was introduced by a diastereoselective rhodium catalyzed cyclopropanation reaction. Keywords: Amino acids; carbenes; cyclopropanation; rhodium; spiro compounds

• two different synthetic strategies: a) cyclopropanation of an α,β-unsaturated ester (compound III, Z = COOR); b) metal-catalyzed cyclopropanation of the corresponding terminal olefin derivative (compound III, Z = H) with a diazoacetate derivative. After having accomplished this key step, intermediate

• [28][29][30][31][32][33] cyclopropanation reaction were attempted (highlighted in Scheme 3). Regrettably, when these reactions were performed under different reaction conditions by changing the base, the solvent, the temperature and the reaction time, only trace amounts of final product 20 were

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

• reactions and to probe the magnetic environment of the concave/convex space around the hydrocarbon bowl. For both classes of functionalization, computational results are reported to complement the experimental observations. Keywords: Bingel–Hirsch reaction; buckybowl; carbon nanomaterials; cyclopropanation

• unit. Representative synthetic reactions of fullerene C60 (2) include cyclopropanation [29][30], [3 + 2] cycloaddition [31][32], [4 + 2] cycloaddition [33], nucleophilic addition [34], and radical addition reactions [35]. Two of the earliest and most widely used reactions, the Bingel–Hirsch reaction

• behavior. Considering the similarity between the curved π-systems of circumtrindene and fullerene C60, we speculated that the Bingel–Hirsch reaction might occur with circumtrindene (6) in the same manner as it does with fullerene C60. Gratifyingly, the cyclopropanation of circumtrindene by the Bingel

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

• alcohol to yield aldehyde 34. Addition of double deprotonated methyl acetoacetate gave β-ketoester 35. Diazotransfer followed by double protection resulted in the formation of compound 36. Rh-catalyzed intramolecular cyclopropanation of this compound gave bicycle 37. Selective removal of the secondary

• 82. Diazotransfer using p-ABSA [86] yielded diazoester 83. Selective rhodium-catalyzed cyclopropanation of the cis-double bond [87][88] of diene 84 [89] furnished cis-divinylcyclopropane 85, which underwent DVCPR upon Kugelrohr distillation at 140 °C to give bicyclic 86. Selective hydrogenation of

• ). Davies and co-worker [91][92] investigated the formal synthesis of the sequiterpene-hydroquinone derivative frondosin B (99, see Scheme 12) [93] via an enantioselective cyclopropanation of trans-piperylene and subsequent divinylcyclopropane rearrangement, to further demonstrate the versatility of their

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• nucleophilic double bound of the allene, forming the intermediate 88. Finally, condensation of the alkylgold 88 onto the carbonyl group led to the bicyclic product 84 (Scheme 23). An interesting example of gold-catalyzed intramolecular cyclopropanation of olefins was recently documented by Maulide and

• -based electrophilc activation of the C=C, with consequent nucleophilic attack by the ylidic carbon onto the internal carbon of the double bond. Finally, the intermediate lactone 92 underwent cyclopropanation, delivering SPh2 as a leaving group (Scheme 24b). 5 Addition to allylic alcohols The use of

• benzoates. Intramolecular [Au(I)]-catalyzed cyclopropanation of alkenes. Stereospecificity in [Au(I)]-catalyzed hydroalkoxylation of allylic alcohols. Mechanistic investigation on the intramolecular [Au(I)]-catalyzed hydroalkoxylation of allylic alcohols. Mechanistic investigation on the intramolecular

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

• with high diastereoselectivity. Moreover, the enantioselective cyclopropanation was not limited to arylated olefins (e.g. styrenes), but allyltrimethylsilane also participated in the process, producing the corresponding silylmethyl cyclopropane as a 5:1 mixture of cis:trans isomers with a good 78% ee

• (Scheme 1). In 2009, the same group extended the utility of this asymmetric cyclopropanation reaction to an intramolecular process that allows the enantioselective synthesis of polycarbocyclic products embedding seven or eight-membered rings [42]. Curiously, the catalytic system based on DTBM-Segphos

• eleven, gold has also demonstrated to be an efficient promoter of intermolecular carbene transfer reactions from diazo compounds to unsaturated systems such as alkenes or alkynes, resulting in cyclopropanation processes [44][45]. The development of an enantioselective variant of this type of reactions

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

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

• dirhodium(II)-catalysed cyclopropanation, and C–H and Si–H insertion reactions [37][38][39]. There are, to the best of our knowledge, no reports in the literature of α-halodiazoacetamides as a substance class. Thus, we wished to expand the substrate scope of one of our published methodologies to encompass

• thermolysis of an α-bromodiazoketone was successfully employed in an intramolecular cyclopropanation reaction [62]. Historically, the thermolysis of diazocarbonyl compounds has been carried out under reflux [63][64][65][66], although examples of low temperature and ambient temperature thermolysis can be found

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• unsaturated building blocks. The approach involved the iterative attachment of a propagating and a terminating building block to a fluorous-tagged initiating building block. Metathesis cascade chemistry was used to “reprogram” the molecular scaffolds. Remarkably, in one case, a cyclopropanation reaction

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• resulted from heating 24 and 193 together [134]. Finally, as shown by Lüttke and Heinrich, the cyclopropanation of the parent system 2 with diazomethane/Cu2Cl2 provided a mixture of twelve cyclopropanation products in very good yield (ca. 90%), from the mono adduct 195 to the dispiro compound 196, i.e. the

Alkenes from β-lithiooxyphosphonium ylides generated by trapping α-lithiated terminal epoxides with triphenylphosphine

• David. M. Hodgson and
• Rosanne S. D. Persaud

Beilstein J. Org. Chem. 2012, 8, 1896–1900, doi:10.3762/bjoc.8.219

• epoxides 8 by using hindered lithium amides, such as lithium tetramethylpiperidide (9, LTMP) [20], and have shown synthetically useful carbene reactivity (e.g., cyclopropanation [21][22], dimerization [23][24][25]). The reaction of carbenes and carbenoids with heteroatom lone pairs is a popular strategy to

Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

• Kyle F. Biegasiewicz,
• Michelle L. Ingalsbe,
• Jeffrey D. St. Denis,
• James L. Gleason,
• Junming Ho,
• Michelle L. Coote,
• G. Paul Savage and
• Ronny Priefer

Beilstein J. Org. Chem. 2012, 8, 1814–1818, doi:10.3762/bjoc.8.207

• cyclopropanation and Michael addition reactions. Although there was no increase in stereocontrol, upon computational evaluation using both M06L and B3LYP calculations, it was revealed that a pseudo six-membered ring exists, through H-bonding of a cubyl hydrogen to the copper core. This decreases the steric bulk

• evaluating this cubane-based ligand with cyclopropanation reactions. When no chiral ligand was added there was a 2.6:1 ratio of trans to cis products with no ee control. We then introduced our cubane-based chiral ligand 1 to our cyclopropanation protocol with four different copper sources (Table 1). The

• in obtaining high stereoselectivity, and thus we decided to switch to Michael addition with organomagnesium and organozinc reagents. Since the copper source that produced the highest ee value with the cyclopropanation above was Cu(I) triflate tetrakisacetonitrile, we decided to initially focus on

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT₂ receptor family

• Adam Pigott,
• Stewart Frescas,
• John D. McCorvy,
• Xi-Ping Huang,
• Bryan L. Roth and
• David E. Nichols

Beilstein J. Org. Chem. 2012, 8, 1705–1709, doi:10.3762/bjoc.8.194

• than for DOI itself. Keywords: cyclopropanation; diazomethane; hallucinogen; 5-HT2A agonist; receptor probe; trans-2-phenylcyclopropylamines; Introduction Among the molecules that have proven very valuable to neuroscientists studying brain serotonin systems is the substituted phenethylamine

• sign of optical rotation [4]. The biological data are consistent with those configuration assignments. Chemistry We reasoned that a palladium-mediated cyclopropanation of the corresponding cinnamic acids would provide the required cyclopropanecarboxylic acid (Scheme 1); which could be readily converted

• chiral auxiliaries in the cyclopropanation step could directly afford the chiral cyclopropane acids [8], but time and resources did not allow us to pursue that approach. Conclusion In conclusion, our strategy to replace the ethylamine side chain of 1a (or 1b) with a cyclopropylamine moiety was successful

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

• is CH3CN unless otherwise mentioned, N values taken from [4][61]). Experimental and calculated rate constants k2 for the reactions of 17b and 17g with 3a and 3b in the presence of 2,6-lutidine in CH2Cl2 at 20 °C [61]. Comparison between experimental and calculated (Equation 1) cyclopropanation rate

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• the enantioselective cyclopropanation with supported copper–bisoxazoline (Cu–BOX) or copper-pyridineoxazoline (Cu–PyOX) complexes and related systems. The oxazoline ligands can be introduced in polystyrene–divinylbenzene (PS–DVB) matrices either by grafting, by reaction with chloromethyl groups of

• preformed resins, or by polymerization of the corresponding bisoxazolines or pyridineoxazolines containing polymerizable vinylic fragments [73][74]. The transformation of those BOX or PyOX moieties into the corresponding Cu complexes allows their use as catalysts for the enantioselective cyclopropanation of

• . Enantioselective hydroformylation of styrene. Enantioselective hydrovinylation of styrene. Enantioselective cyclopropanation of styrene catalyzed by supported Cu–BOX, Cu–PyOX and Rh–PyBOX catalysts. Continuous hydrogenation of acetophenone coupled with the kinetic resolution of the product. Kinetic resolution of