Recent advances in the electrochemical construction of heterocycles

• Robert Francke

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

• Michael addition/ring closure with in situ generated quinones (section 2.2) and sequential cyclizations involving acyliminium species and alkoxycarbenium ions (section 2.3) represent the majority of recently reported intermolecular electrochemical cyclizations. Cases which do not fall into any of these

• N-acyliminium species have been developed, resulting in the synthesis of a number of lactams and lactam-derived heterocycles [52]. One representative example is depicted in Scheme 10, where dipeptide 25 cyclizes via intramolecular nucleophilic attack of the hydroxy group on the anodically generated

• N-acyliminium unit [53]. While this reaction proved to be very useful for the cyclization of simple amino acid derivatives, major limitations were encountered when more complicated systems were oxidized [52]. As outlined before, amide groups exhibit rather high oxidation potentials in the order of

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• glycol in the presence of tetrabutylammonium hydrogen sulfate as both an acid and a phase-transfer catalyst (Scheme 28) [100]. As the authors suggested, the formation of intermediate N-acyliminium ion from aldehyde 75 and (thio)urea was the key step of the reaction. Protonation of aldehyde 75 by

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• ; cyclization; Diels–Alder; inverse electron demand; N-acyliminium ion; tert-enamide; Introduction Fused indoline, isoindoline, quinoline and isoquinoline substructures are found in many natural products and bioactive synthetic compounds (Figure 1). For example, nuevamine is a naturally-occurring isoindolo[1,2

• isoindolo[2,1-a]quinolone derivatives involves N-acyliminium ions or appropriate electron-deficient Schiff bases and subsequent [4 + 2] inverse-demand hetero-Diels–Alder cycloadditions with alkenes [11][12][13][14][15][16][17]. Vinylic systems from isoeugenol [11], cyclopentadiene [12], enones [13], vinyl

• ethers [14] and enolic 1,3-diketo compounds [15], have been reported to react with N-acyliminium ions obtained either from 2-formylbenzoic acid and anilines [11][12] or from N-acyliminium ions prepared from N-arylphthalimides [13][14][15]. Nucleophilic substitution of N-aryl-3-hydroxyisoindolinones from

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

• presence of different amounts of catalyst (from 0 to 10 mol %) and/or 2,6-lutidine hydrochloride as a suitable proton source, the authors proposed the mechanism depicted in Scheme 16. The process involves the addition of gold-acetylide I to the activated N-acyliminium salt II resulting from the reaction

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• of (−)-epimyrtine have been described to date including the intramolecular allylsilane N-acyliminium ion cyclization [6], the organocatalytic aza-Michael reaction [7], the intramolecular Mannich reaction [8], and the iminium ion cascade reaction [9][10]. More efficient, convenient and highly

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• and indoles are then added to the N-acyliminium ions 68b to provide the amidoalkylation products 69. Alternatively, the use of only persulfate at 55 °C afforded the same products. However, higher yields and better selectivities were generally observed with the photocatalytic process. Intercepted by

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• electrophilicity the imine failed to cyclize under the conditions reported earlier. A literature search revealed that the acyliminium strategy has been used to overcome this defect [25][36][37]. However, one has to cleave the N-acyl group of the product in order to generate the desired compound, and thus, an

Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates

• Julien Lefranc,
• Alberto Minassi and
• Jonathan Clayden

Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70

• carbon atom β to the nitrogen atom [1][2]. The resulting intermediate iminium or N-acyliminium ions are electrophilic, and may themselves trap a nucleophile at the position α to the nitrogen substituent. However, we [3][4] and others [5][6][7] have shown that this typical reactive polarity may be

Synthesis of a library of tricyclic azepinoisoindolinones

• Bettina Miller,
• Shuli Mao,
• Kara M. George Rosenker,
• Joshua G. Pierce and
• Peter Wipf

Beilstein J. Org. Chem. 2012, 8, 1091–1097, doi:10.3762/bjoc.8.120

• , the addition to in situ prepared N-acyliminium species, and ring-closing metathesis (RCM) were key steps in the preparation of a tricyclic isoindolinone scaffold. An unusual alkene isomerization process during the RCM was identified and studied in some detail. Chemical diversification for library

• ; epoxide aminolysis; hydrozirconation; isoindolinones; metathesis; N-acyliminium ion; Introduction Isoindolinones represent a common scaffold seen in naturally occurring compounds such as magallanesine [1], lennoxamine [2] and clitocybin A [3], or drug candidates such as pagoclone [4] (Figure 1). These

• synthetic building blocks, a variety of approaches for the preparation of these heterocycles have been explored [11][12][13][14][15][16][17][18]. Previously, we reported on the addition of organometallic reagents to in situ generated N-acyliminium ions [19]. This methodology applies to a variety of

A concise synthesis of 3-(1-alkenyl)isoindolin-1-ones and 5-(1-alkenyl)pyrrol-2-ones by the intermolecular coupling reactions of N-acyliminium ions with unactivated olefins

• Nianhong Lu,
• Lihong Wang,
• Zhanshan Li and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 192–200, doi:10.3762/bjoc.8.21

• the coupling reactions of N-acyliminium ions produced from 3-hydroxyisoindol-1-ones or 5-hydroxy-1-pyrrol-2-ones with unactivated olefins in the presence of BF3·OEt2 at room temperature. For most of the olefins, the reactions afforded the Csp3–Csp2 cross-coupling products, but for the α-methylstyrene

• and 1-hexene, the Csp3–Csp3 cross-coupling products were obtained. Keywords: 3-(1-alkenyl)isoindol-1-ones; 5-(1-alkenyl)pyrrol-2-ones; coupling reaction; 2,3-dihydro-3-hydroxyisoindol-1-one; 2,5-dihydro-5-hydroxypyrrol-2-one; N-acyliminium ions; Introduction The coupling of alcohols with alkynes

• ]. We have long been interested in the reactions of N-acyliminium ions produced easily by the Brønsted acid and Lewis acid catalyzed dehydroxylation of α-hydroxyamides [12][13][14]. The high electrophilicity of these species is very suitable for electrophilic addition to carbon–carbon multiple bonds

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• three-component process allowing the synthesis of α-substituted amides. This methodology relied on the oxidative addition of an N-acyliminium species, generated in situ from an imine and an acid chloride, to a Pd(0) complex, furnishing a stable chelated palladium adduct 1, which was isolated and fully

• , based on a similar strategy, through the assembly of four components, namely, imines, acid chloride and carbon monoxide. The process is thought to begin with formation of a münchnone 5, resulting from oxidative addition of an acyliminium species to Pd(0), followed by CO insertion and β-hydride

A practical microreactor for electrochemistry in flow

• Kevin Watts,
• William Gattrell and
• Thomas Wirth

Beilstein J. Org. Chem. 2011, 7, 1108–1114, doi:10.3762/bjoc.7.127

• trapped immediately after generation. In the "cation flow" method, a carbocation is generated continuously in a flow system by low temperature electrolysis. The generation of the cation can be monitored by a FTIR spectrometer in the flow system. The electrochemically generated N-acyliminium ions can then

• the product selectivity. Cycloadditions using the N-acyliminium ions as heterodienes with a variety of dienophiles, such as alkenes and alkynes, give the corresponding [4 + 2] cycloaddition products in high yields [10]. The same authors also reported a successful polymer synthesis using the same

• technique by adding a monomer to the initiator (N-acyliminium ions) followed by micromixing and the addition of the terminator (diisopropylamine) in a subsequent micromixer. This was considered to be a superior technique to the batch method as the molecular weight distribution of the polymer 3 decreased in

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

• Erwan Le Gall,
• Antoine Pignon and
• Thierry Martens

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates is described. This route involves the formation of an imine, which is used without isolation, followed by its activation by the carbonyl-containing electrophile and the trapping of the acyliminium by an organozinc reagent. Most

• steps are conducted concomitantly to render the procedure as practical and straightforward as possible. Therefore, the whole experimental protocol takes less than two hours. Keywords: acyliminium; amides; carbamates; multicomponent reactions; organozinc reagents; Introduction Diarylmethylamines

• addition of aromatic nucleophiles onto N-acyliminium intermediates, formed in situ by reaction of imines with carbonyl-containing electrophiles. In this latter area, several studies have shown that some electron-enriched arenes can be used as nucleophiles and add efficiently onto the iminium carbon, either

Total synthesis of the indolizidine alkaloid tashiromine

• Stephen P. Marsden and
• Alison D. McElhinney

Beilstein J. Org. Chem. 2008, 4, No. 8, doi:10.1186/1860-5397-4-8

• centres on the stereoselective construction of the indolizidine core by capture of an electrophilic acyliminium species by a pendant allylsilane. The key cyclisation precursor is constructed using olefin cross-metathesis chemistry, which has the potential to facilitate both racemic and asymmetric

• -mediated reductive imide-olefin cyclisation [10]. Our own approach [14] utilises an intramolecular addition of an allylsilane to an N-acyliminium ion to deliver the [4.3.0]-azabicyclic (indolizidine) skeleton 2 (Scheme 1), wherein the pendant vinyl group acts as a handle to install the hydroxymethyl

• sidechain found in tashiromine. The synthesis of azabicyclic assemblies by intramolecular allylsilane/N-acyliminium cyclisations was first studied by Hiemstra and Speckamp [16], who prepared their functionalised allylsilane cyclisation precursors (such as 3) by alkylation of cyclic imides with reagent 4 (X

A convenient allylsilane- N-acyliminium route toward indolizidine and quinolizidine alkaloids

• Roland Remuson

Beilstein J. Org. Chem. 2007, 3, No. 32, doi:10.1186/1860-5397-3-32

• of an allylsilane on an N-acyliminium ion. In this paper, we describe the synthesis of racemic indolizidine 167B and chiral indolizidines: (-)-indolizidines 167B, 195B, 223AB, (+)-monomorine, (-)-(3R,5S,8aS)-3-butyl-5-propylindolizidine and (-)-dendroprimine. Next, we relate the synthesis that we

• alkaloids ideal targets for total synthesis. We have developed a new method to generate bicyclic indolizidine and quinolizidine compounds based on an intramolecular cyclisation of acyliminium ions substituted by an allylsilyl side chain as an internal π-nucleophile (Scheme 1). [6] This reaction has proven

• and the important biological activities of the compound make this alkaloid an ideal target for total synthesis. [9][10][11][12][13][14][15][16] I 1.1 Intramolecular cyclisation We have found that intramolecular cyclisation of an allylsilane on an acyliminium ion constituted an excellent route to

Generation of pyridyl coordinated organosilicon cation pool by oxidative Si-Si bond dissociation

• Toshiki Nokami,
• Ryoji Soma,
• Yoshimasa Yamamoto,
• Toshiyuki Kamei,
• Kenichiro Itami and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2007, 3, No. 7, doi:10.1186/1860-5397-3-7

• " method, which involves the irreversible oxidative generation and accumulation of highly reactive cations in the absence of nucleophiles [1][2][3][4][5]. Heteroatom-stabilized carbocations, such as N-acyliminium ion pools and alkoxycarbenium ion pools have been generated based on oxidative C-H, C-Si, and