Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• -rearrangement metathesis as key steps. Here, we used a simple starting material such as dicyclopentadiene. Keywords: allylation; Beckmann rearrangement; lactams; oximes; ring-rearrangement metathesis; Introduction The Beckmann rearrangement (BR), a well-known protocol for the conversion of ketoxime to an

• conditions gave the saturated ketone 7 [32] (Scheme 1). Later, tricyclic ketone 7 was reacted with NH2OH·HCl in the presence of NaOAc in dry MeOH at rt to give a mixture of oximes 8a and 8b and this mixture was subjected to a BR under different reaction conditions, like (a) p-TsCl, rt, 15 h, CH3CN (b) p-TsCl

• , reflux, 15 h, CH3CN (c) PPA, reflux for 20 min. Surprisingly, in all these instances no rearrangement product was observed. Interestingly, when the mixture of oximes 8a and 8b was treated with TsCl in the presence of NaOH at rt lactams 9a and 9b were obtained in 66% combined yield for two steps (9a:9b

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• the easy access to nitroolefins in large variety, the C–C bond formation with the introduction of two nitro groups in a 1,4-distance and the conversions of the nitro group by reduction to oximes and amines, the conversion into aldehydes and ketones via the Nef reaction and base catalyzed condensations

• anion to a carbonyl group followed by elimination of water from the resulting alcohol. The nitroolefin can be reduced at the nitro group, at the double bond and simultaneously at both groups. In acidic medium the nitro group is reduced between −0.25 V to −0.55 V vs SCE to mixtures of syn/anti-oximes in

• 85% to 92% yield at a mercury pool cathode and with slightly lower yields at a graphite cathode [5][6][7][8]. The current controlled reduction of alkyl- and aryl-substituted nitroalkenes in acidic medium affords mixtures of ketones and oximes in yields of 39% to 72% [9] and 55% to 91% [10

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• ] and biological chemistry [249][250][251][252]. In the past, the Jacobsen group has used chiral (salen)Al complexes [253] as catalysts for the asymmetric 1,4-addition of azide [254], cyanide [219], substituted nitriles [255] and oximes [256] to α,β-unsaturated imides. The authors used these previous

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• Carolin Edinger Jorn Kulisch Siegfried R. Waldvogel Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128 Mainz, Germany 10.3762/bjoc.11.34 Abstract The electrochemical generation of menthylamines from the corresponding menthone oximes equipped with an

• additional substituent in position 8 is described. Due to 1,3-diaxial interactions a pronounced diastereoselectivity for the menthylamines is found. Keywords: cathodic reduction; chiral amines; electrosynthesis; menthylamines; oximes; Introduction Optically active amines serve as powerful and versatile

• starting from commercially available (+)-pulegone (4, Scheme 3). An important feature of this sequence is the initial introduction of a sterically demanding moiety R in position 8 via cuprate addition. After conversion to menthone oximes 7 within the second step, R is supposed to enhance the

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• lower temperature (50 °C instead of 100 °C, as in the case of CH-reagents 22 and 23) [53]. The ortho-acetoxylation and methoxylation of O-methyl aryl oximes 31 with Pd(OAc)2 combined with such oxidants as oxone, potassium persulfate, and (diacetoxyiodo)benzene (Scheme 7, coupling products 32 and 33

• [55], and O-acetyl aryl oximes [56] in the presence of the Pd(OAc)2/PhI(OAc)2 system were described. The ruthenium-catalyzed ortho-acyloxylation of acetanilides 39 with carboxylic acids in the presence of AgSbF6 and ammonium persulfate afforded products 40 (Scheme 8) [57]. This method can be used for

• of iodine(III) oxidants (50–130 °C, Scheme 19 and Scheme 20). Under similar conditions methyl groups of N-(quinolin-8-yl)amides were acetoxylated using the Cu(OAc)2 catalyst (50 mol %) and AgOAc (3 equiv) as acetoxylating agent. The acetoxylation of alkyl groups of O-acetyl oximes 102 taking place in

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• rather expensive; therefore efforts were made to replace them with cheaper analogues. One successful approach included iron(III) acetylacetonate in acetic acid as catalytic agent (Scheme 16) [37], whereby O-acetyl oximes obtained from 2′-arylacetophenones underwent N–O bond cleavage and intramolecular N

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• case due to the Thorpe–Ingold effect [46]. Recently, Zeng, Little and co-workers reported a new electrochemical method for the preparation of 3,5-disubstituted isoxazoles from chalcone oximes 20 (Scheme 8) [47]. The electrolysis of 20 is carried out in an undivided cell under galvanostatic conditions

• ester 12. Preparation of pyrrolidines and tetrahydrofurans via Kolbe-type electrolysis of unsaturated carboxylic acids 16. Anodic cyclization of chalcone oximes 19. Generation of N-acyliminium (23) and alkoxycarbenium species (24) from amides and ethers with and without the use of electroauxiliaries

N–O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines

• Jaipal R. Nagireddy,
• Geoffrey K. Tranmer,
• Emily Carlson and
• William Tam

Beilstein J. Org. Chem. 2014, 10, 2200–2205, doi:10.3762/bjoc.10.227

• -hydroxyimines 3, β-hydroxynitriles 4, β-aminoketones 5, γ-aminoalcohols 6 and oximes 7 can all be readily attained through ring cleavage of 2-isoxazolines using suitable reagents for each transformation (Scheme 1) [1][2][3][4][5][6][7]. In recent years, there has been considerable interest in applying this

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• demonstrated the isolation and synthetic utility of a nucleoside phosphonium salt [28]. Thus, to us the reaction of oximes with BOP was an intriguing result, leading us to query whether a benzotriazolyl intermediate, rather than a phosphonium ion, was formed en route to the cyanide. This line of reasoning

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

• acids 55 (Scheme 7) [59]. The synthesis of an mGluR agonist was achieved using chloromethyl phosphonamide 28d [60][61], as discussed later in this review. Replacing Michael acceptors with oximes in the reaction with chloroallyl phosphonamide 47a leads to the stereoselective formation of cis-aziridines

• 57 (Scheme 8) [62]. Thus, addition of the anion of phosphonamide 47a to tert-butyl glyoxylate O-protected oximes affords the corresponding aziridine adducts 57 in excellent diastereoselectivity in a Darzens-type reaction via intermediate 56. This aziridination methodology was then used in the

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• . Oximes derived from (intermediate) 5-alkynyl-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carbaldehydes were transformed into the corresponding 1H-pyrazolo[4,3-c]pyridine 5-oxides by silver triflate-catalyzed cyclization. Detailed NMR spectroscopic investigations (1H, 13C, 15N and 19F) were undertaken with

• reaction of the thus obtained 5-alkynyl-1H-pyrazole-4-carbaldehydes in the presence of tert-butylamine [17]. Furthermore, we showed that the oximes derived from the before mentioned 5-alkynylpyrazole-4-carbaldehydes can be transformed into the corresponding 1-phenylpyrazolo[4,3-c]pyridine 5-oxides [17

• gain access to the corresponding N-oxides of type 7, aldehydes 4a–c were transformed into the corresponding oximes 6a–c by reaction with hydroxylamine hydrochloride in ethanol in the presence of sodium acetate (Scheme 1). Subsequent treatment of the oximes with AgOTf in dichloromethane [29] finally

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• the dehydration of oximes 12 to form nitriles 13. Capitalizing on the fact that 1 is formed as a byproduct from 3a,b in each of these reactions, Denton and co-workers have recently combined the Masaki–Fukui reaction with many of the functional group transformation outlined in Scheme 2, in one-pot

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• led to nearly quantitative hydrolysis of the dioxolane affording diol oxime 20 as 95:5 mixture of E- and Z-isomers. However, if solid NaOH was added to the reaction mixture and heated for several hours, the dioxolane survived, affording a 1:1 mixture of E/Z-oximes, which were tosylated after short

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

• ozonolysis of alkenes, the cross-ozonolysis of alkenes with carbonyl compounds, and the cross-ozonolysis of О-alkylated oximes in the presence of carbonyl compounds (Griesbaum coozonolysis). 2.1. Ozonolysis of alkenes According to the mechanism proposed by R. Criegee [268][269] the ozonolysis of alkenes 163

•  44) [256]. 2.3. Cross-ozonolysis of O-alkyl oximes in the presence of carbonyl compounds (Griesbaum co-ozonolysis) In 1995, K. Griesbaum and co-workers reported a new type of cross-ozonolysis [295]. This method enables the synthesis of tetrasubstituted ozonides 176 by an ozone-mediated reaction of О

• -alkyl oximes 174 with ketones 175 (Scheme 45, Table 13). The selective synthesis of ozonides has attracted great interest because it allows the preparation of compounds exhibiting high antiparasitic activity. The Griesbaum method is widely applicable and allows the selective synthesis of symmetrical and

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• (Table 1, entry 10), without traces of the corresponding α-aminoamide. Different types of activated substrates displaying C=N bonds (N-sulfinylimines, oximes and hydrazones) were studied, but none of them reacted productively with isocyanides under the described conditions. Finally, the reaction with

Gallium-containing polymer brush film as efficient supported Lewis acid catalyst in a glass microreactor

• Rajesh Munirathinam,
• Roberto Ricciardi,
• Richard J. M. Egberink,
• Jurriaan Huskens,
• Michael Holtkamp,
• Herbert Wormeester,
• Uwe Karst and
• Willem Verboom

Beilstein J. Org. Chem. 2013, 9, 1698–1704, doi:10.3762/bjoc.9.194

• X-ray photoelectron spectroscopy (XPS). XPS revealed the presence of one gallium per 2–3 styrene sulfonate groups of the polymer brushes. The catalytic activity of the Lewis acid-functionalized brushes in a microreactor was demonstrated for the dehydration of oximes, using cinnamaldehyde oxime as a

• model substrate, and for the formation of oxazoles by ring closure of ortho-hydroxy oximes. The catalytic activity of the microreactor could be maintained by periodic reactivation by treatment with GaCl3. Keywords: dehydration of oximes; flow chemistry; gallium; microreactors; Lewis acid catalysis

• substrate scope of the dehydration of oximes was extended using the same reaction conditions as above (Table 2). 4-Nitrobenzaldehyde oxime (3, Table 2, entry 1) resulted in a conversion of 62% within 13 min reaction time, while for the batch reaction, using gallium(III) triflate as a catalyst, 16 h at 120

Re₂O₇-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

• Wantanee Sittiwong,
• Michael W. Richardson,
• Charles E. Schiaffo,
• Thomas J. Fisher and
• Patrick H. Dussault

Beilstein J. Org. Chem. 2013, 9, 1526–1532, doi:10.3762/bjoc.9.174

• lack of reactivity of ozonolysis-derived 1-methoxyhydroperoxides towards methanolic acid may mask a rapid degenerate exchange [27]. The failure of the perrhenate to catalyze formation of N,O-acetals was initially perplexing. However, reported perrhenate-promoted dehydrations of amides and oximes

Interplay of ortho- with spiro-cyclisation during iminyl radical closures onto arenes and heteroarenes

• Roy T. McBurney and
• John C. Walton

Beilstein J. Org. Chem. 2013, 9, 1083–1092, doi:10.3762/bjoc.9.120

• Roy T. McBurney John C. Walton EaStCHEM School of Chemistry, University of St. Andrews, St. Andrews, Fife, KY16 9ST, UK 10.3762/bjoc.9.120 Abstract Sensitised photolyses of ethoxycarbonyl oximes of aromatic and heteroaromatic ketones yielded iminyl radicals, which were characterised by EPR

• derivatives of oximes with various aromatic and heteroaromatic architectures (Figure 1). Compounds 1a–f contain comparatively rigid arms and their aromatic acceptors range from electron-withdrawing to electron-releasing in character. In compounds 2a,b and 3 heteroarenes replace the benzene rings and in 4 the

• affecting this are weighed up. Results and Discussion The arene and heteroarene-based oxime carbonates 1 and 2 were prepared as described previously by reaction of the corresponding aromatic ethanone oximes with ethyl chloroformate [26]. Precursors 3 and 4 were made in a similar way from the oximes of 2

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• that benzoates of hydroxamic acids, oximes and related derivatives reacted nicely with stannyl radicals to furnish the corresponding nitrogen radicals under mild conditions [7]. These could be readily incorporated into various radical sequences leading to complex nitrogen-containing scaffolds. One

Synthesis of SF₅-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes

• Petr Beier and
• Tereza Pastýříková

Beilstein J. Org. Chem. 2013, 9, 411–416, doi:10.3762/bjoc.9.43

• found to be problematic [9]. The reactions of nitrobenzene with arylacetonitriles gave oximes 2 (Figure 1) [11]. Pentafluorosulfanyl-containing compounds (first synthesized by Sheppard in 1960 [12][13]) are relatively rare, and their chemistry is underdeveloped. These derivatives are promising for

• access to new SF5-substituted aromatic and nitrogen-containing heteroaromatic compounds. Substitution products 1, oximes 2 and nitro-(pentafluorosulfanyl)benzenes 3 and 4. Proposed mechanism of the Davis reaction giving benzisoxazoles. Synthesis of SF5-substituted quinolines and mefloquine analogues by

N-Heterocyclic carbene-catalyzed direct cross-aza-benzoin reaction: Efficient synthesis of α-amino-β-keto esters

• Takuya Uno,
• Yusuke Kobayashi and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2012, 8, 1499–1504, doi:10.3762/bjoc.8.169

• migration of the N-acyl glycine derivatives [18]. The other consists of C–N bond-forming reactions, such as (c) a rhodium-catalyzed N–H insertion reaction with α-diazo-β-keto esters [19][20][21], and (d) α-oxidation of β-keto esters to the corresponding oximes and the subsequent hydrogenation [22]. However

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• Sosale Chandrasekhar V. Mohana Rao Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India 10.3762/bjoc.8.161 Abstract The titled approaches were effected with various 2-substituted benzoylacetic acid oximes 3 (Beckmann) and 2-substituted malonamic acids 9 (Hofmann

• complicated by competing deacylation, hydroxamic acid formation, etc. We are only aware of two reports [8][9] of the Beckmann rearrangement of β-keto ester oximes. A particular problem was the formation of isoxazolone byproducts, which apparently limited the synthesis to α,α-disubstituted derivatives

• preparation of 1 is also presented herein). Ketone 1 was α-alkylated in high yields to various 2 via sodium hydride deprotonation and reaction of the resulting enolate with a variety of alkyl bromides or iodides. Alkyl derivatives 2 may be converted conventionally to the corresponding oximes 3. The Beckmann

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• , phosphinites, phosphonates, imines, diimines, oximes, oxime ethers and diketones were selected for the screening (Figure 2). Several of these compounds have been employed in diaryl ether syntheses before [22][23][24]. As a starting point, N,N-dimethylglycine (L1) introduced by Ma et al. [22][25] in combination

• screening, as can be seen by comparison of L28, L32, and L33. Furthermore, oxime ethers, which, to the best of our knowledge, represent a new class of ligands for Ullmann-type couplings, were also screened in the model reaction. All tested oxime ethers and oximes showed catalytic activity, although the

• substrate conversion was lower compared to the amino acid-derived ligands. The catalytic activities of the oximes did not, however, differ from those of the oxime ethers. On the other hand, the salicyl aldehyde-derived oxime ether and oxime ligands [31] showed only poor substrate conversions in comparison

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• substituents represents a promising approach for the development of scavengers able to detoxify highly toxic nerve agents. Keywords: acetylcholinesterase; cyclodextrins; cyclosarin; neurotoxic organophosphonates; oximes; Introduction Cyclodextrins, cyclic oligosaccharides composed of α-1,4-linked D-glucose

• reactive unit and allowing it to mediate another reaction. Here, we describe our first results in this project, involving a series of β-cyclodextrin derivatives with substituents on the primary face of the cyclodextrin ring, containing oximes as nucleophilic groups. Oximes are well-known antidotes for the

• treatment of OP poisonings. Their mode of action involves reactivation of the OP-inhibited acetylcholinesterase [29], yet previous work has also indicated that certain oximes are able to cleave OPs directly [30]. We show that some of our cyclodextrin derivatives efficiently reduce GF concentrations in

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

• Imines and oximes are versatile synthetic intermediates for the preparation of dyes, pharmaceuticals, and agricultural chemicals. Sun et al. have reported a multi-task Au/hydroxyapatite reagent for the heterogeneous catalyzed oxidation of alcohols and amines to imines or oximes [56]. N-alkylation of

• . In addition to intermolecular addition, Mukherjee and Widenhoefer recently reported a gold(I)-catalyzed intramolecular amination of allylic alcohols 130 with alkylamines (Scheme 23) [61]. 3.2 Imines as nucleophiles Gold-catalyzed cyclizations of O-propioloyl oximes via C–N bond formation followed by