Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf)₃ catalyst in the reaction selectivity

• Natividad Herrera Cano,
• Jorge G. Uranga,
• Mónica Nardi,
• Antonio Procopio,
• Daniel A. Wunderlin and
• Ana N. Santiago

Beilstein J. Org. Chem. 2016, 12, 2410–2419, doi:10.3762/bjoc.12.235

• effective electrophilic activating agent for the formation of the bisimine and promotes the subsequent steps (intramolecular nucleophilic attack and the following 1,3-hydride shift), finally affording the 1,2-disubstituted imidazoles (b). In contrast, path ii is a non-catalyzed reaction. In path ii, when

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• , it has to be noted that the trans-THF was not directly formed in an oxidative cyclization reaction but rather through a subsequent sequential solvolysis/hydride shift/intramolecular reduction cascade. Another total synthesis of cis-sylvaticin (40) has been published by Brown and co-workers in 2008

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• effect of the ketone involved. More importantly, when a ketone is used in the reaction the formed unstable [4 + 1] cycloaddition adduct could not undergo a [1,3]-alkyl shift. On the other hand the reaction with an aldehyde allows further conversion through a [1,3]-hydride shift to form a stable and

• ] cycloaddition adduct could further proceed with a retro-aza–ene reaction via a concerted [1,5]-hydride shift. We first explored the reaction of 2-aminopyridine (2a), isatin (3a) and tert-butyl isocyanide (4a). Under the classical reaction conditions (entry 1, Table 1), the product 1a was isolated only in 4

• species from 2-aminopyridine and isatin which then undergoes a formal [4 + 1] cycloaddition with isocyanide to generate a spiro intermediate b. The spiro compound then undergoes a retro-aza–ene reaction via a [1,5]-hydride shift resulting in an aromatic imidazo[1,2-a]pyridine having an isocyanate

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• ) fragment in a bidentate fashion and undergoes a redox isomerization reaction wherein the carbinol proton performs a 1,2-hydride shift. The resulting vinylruthenium intermediate can be seen as a resonance structure of a ruthenium carbene, which coordinates to a pendant alkene, performs a [2 + 2

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• insertion reaction was more rapid than a 1,2-hydride shift or rearrangement, and the bridged product 14 was obtained in 87% yield. This compound was advanced to synthesize the natural product deoxystemodin [21][22][23][24][25]. Grainger reported an approach to synthesize the bridged core of ingenol via C–H

• (i.e., 86 to 87, Scheme 20) [89]. Surprisingly, no reaction was observed in the absence of the Rh catalyst, suggesting that it may be involved in the transformation of the hydrazone to 87. While the intermediate alkyl carbene 88 could potentially undergo a 1,2-hydride shift to give the alkene 90 in a

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• is interrupted as in the zwitterion 4. The latter would represent the intermediate if a hydride shift occurred in the imine before the decarboxylation step (Figure 7, upper row). In contrast, the zwitterions 5 and 6 readily lose CO2 upon geometry optimization, since the negative charge is efficiently

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• rings that are transformed in only one or two enzyme-promoted reactions. These reactions involve generation of a carbocation by protonation or loss of a diphosphate group followed by cyclization, alkyl shift, hydride shift and/or proton transfer reactions to generate new, more complex, carbocations

• pimar-15-en-8-yl cation are considered, then a product ratio of approximately 2:1, in favor of miltiradiene formation, is found, i.e., some trajectories actually connect to a carbocation formed by a 1,2-hydride shift of the pimar-15-en-8-yl cation (Figure 10, orange). This result suggests that

• preorganization of the substrate into a conformation that disfavors the 1,2-hydride shift actually promotes miltiradiene formation. Finally, when dynamics trajectories were initiated from the region of the 1,6-proton transfer transition state associated with proton migration to the si face of the C=C double bond

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• are conceivable for explaining these conversions. Deuterium labelling experiments exclude the [1,4]-hydride shift as the first step. A computational study scrutinized the reaction channels of these tandem conversions starting by [1,5]-, [1,7]- and [1,9]-H shifts, revealing that this first step is the

• that ortho-(1,3-dioxolan-2-yl)benzylidenemalonates 1 undergo tandem hydride shift/cyclization sequences leading to the corresponding indan-1-one-2,2-dicarboxylates 2. Remarkably, the first step of these processes consists of an uncommon [1,4]-hydride shift of the acetalic H atom following the

• ]-hydride shift of its acetalic H atom toward the exocyclic C4 carbon atom of the fulvene fragment (note the numbering in the Scheme 2). At this point it is worth noting that other possible H migrations were not ruled out at the outset of this investigation. For example, C5 and C7 may be the respective

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• group. The energy barrier of a distorted benzene ring would then be compensated by rearomatization in 23 after intramolecular Diels–Alder reaction. This mechanism would involve a 1,2-hydride shift and a nucleophilic attack of water at C-2’. The second discussed route starts with a nucleophilic attack of

• (42) and B (43) provides an interesting example (Scheme 7) [61]. The proposed mechanism starts with isomerization of farnesyl diphoshate (FPP, 35) to nerolidyl diphosphate (36) followed by 1,10-ring closure to the helminthogermacradienyl cation (37). A 1,3-hydride shift to the allylic cation 38 and

• attack of water gives the neutral intermediate germacrene D-4-ol (39). Reprotonation induces the formation of the bicyclic system 40, which can rearrange via two sequential 1,2-hydride shifts to the cation 41. The attack of the hydroxy function and either a 1,2-hydride shift or a Wagner–Meerwein

Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolecular [1,5]-hydride shift/isomerization reaction

• Chun-Huan Jiang,
• Xiantao Lei,
• Le Zhen,
• Hong-Jin Du,
• Xiaoan Wen,
• Qing-Long Xu and
• Hongbin Sun

Beilstein J. Org. Chem. 2014, 10, 2892–2896, doi:10.3762/bjoc.10.306

• Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolcular [1,5]-hydride shift/isomerization reaction has been realized, using the inherent reducing power of 3-pyrrolines. A series of N-arylpyrrole containing amines are obtained in high yields. Keywords

• : catalysis; C–H activation; hydride-shift; Lewis acid; redox reaction; Introduction The direct and selective functionalization of the inactive C(sp3)–H bond constitute an economically attractive strategy for organic syntheses [1][2][3][4][5][6][7][8][9][10]. Until now, a number of transition metals can be

• reduced to 33% even under high temperature. Notably, according to the 1H NMR spectrum of the crude product, the reaction with phenylamine using Zn(OTf)2 as the catalyst afforded only the corresponding imine product, indicating that the [1,5]-hydride shift/isomerization reaction did not occur. To our

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• Knoevenagel–[1,5]-hydride shift cyclization reaction of a 4-aryl-2-phenyl-1,4-benzoxazepine derivative obtained from flavanone. The relative configuration of products were determined by the correlation of 3JH,H coupling data with the geometry of major conformers accessed by DFT conformational analysis

• cellular injuries in human neuroblastoma SH-SY5Y cells in the range of those of positive controls. Keywords: 1,4-benzoxazepine; diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization; neuroprotective; tert-amino effect; TDDFT-ECD calculation; Introduction The 1,4-benzoxazepine structural

• neuroprotective condensed 2-phenyl-1,4-benzoxazepines rac-7a,b through the diastereoselective domino Knoevenagel–1,5-hydride shift cyclization reaction rac-5→rac-7a,b from the readily available 4-aryl-2-phenyl-1,4-benzoxazepine derivative, rac-5 (Scheme 1). Ring-closure transformations involving C(sp3)–H bond

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• case of amine additions to ynylideneindolone intermediates 11 we recently could show by experimental and computational studies that the terminal Michael addition proceeds in a stepwise fashion with the intermediacy of an allenyl enol that undergoes a rapid, irreversible 1,5-sigmatropic hydride shift

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

• ). After loss of the pyrophosphate group and double cyclization, a 1,3-hydride shift and Wagner–Meerwein rearrangement leads to the naturally occurring ent-atisir-16-ene (231). Oxidative incorporation of nitrogen, which might be derived from β-aminoethanol, generates the atisine-type skeleton 232

Gold-catalyzed cyclization of allenyl acetal derivatives

• Dhananjayan Vasu,
• Samir Kundlik Pawar and
• Rai-Shung Liu

Beilstein J. Org. Chem. 2013, 9, 1751–1756, doi:10.3762/bjoc.9.202

• deuterium labeling experiments supports a 1,4-hydride shift of the resulting allyl cationic intermediates because a complete deuterium transfer is observed. We tested the reaction on various acetal substrates bearing a propargyl acetate, giving 4-methoxy-5-alkylidenecyclopent-2-en-1-ones 4 via a degradation

• cyclopentenone 4e. The deuterium labeling experiment of the d1-1a→d1-4a transformation (Scheme 2, reaction 1) indicates that one methylene proton of 4a is derived from the original acetal group. Accordingly, we postulate a 1,4-hydride shift [21][22] for the intermediate transformation B→C. We excluded an

• diffraction study (crystallographic data are provided in Supporting Information File 1). Formation of this product is postulated to arise from the attack of the methoxy anion at the acetyl group of the corresponding allyl cation E, a process not involving a 1,4-hydride shift. This alternative pathway

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• , which contains two tertiary amines and is readily obtainable by an acid-promoted hydride shift process [52][53][54], was also exposed to oxidative conditions (Scheme 1, reaction 2). We had hypothesized that quinazolinone 32 might be formed in this reaction by the debenzylation of an intermediate iminium

Caryolene-forming carbocation rearrangements

• Quynh Nhu N. Nguyen and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2013, 9, 323–331, doi:10.3762/bjoc.9.37

• ppm) [20], it is well downfield of shifts predicted for hydrides involved in three-center two-electron bonding arrays (e.g., see Supporting Information File 1 for a model transition-state structure for a 1,2-hydride shift with a predicted chemical shift of +1.9 ppm) [49][50][51] and approximately 2

• ). The former, TS-FG, resembles a transition-state structure for a typical 1,2-hydride shift, but the predicted chemical shift of the bridging hydrogen in this structure is +4.7 ppm. The developing close contact with the C3=C15 π-bond (the H---C15 distance is only 2.32 Å in TS-FG) also brings this

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• plausible mechanism for these reactions is depicted in Scheme 3. After initial imine formation, a Brønsted acid promoted 1,5-hydride shift occurs yielding an imino-amine intermediate. Cyclization of the newly formed amine affords the desired aminal product. In 2011, Seidel and co-workers reported an indole

• -annulation cascade reaction with N,N-(dialkylamino)benzaldehydes, a process in which a 1,5-hydride shift occurs followed by larger ring formation [16]. After the evaluation of different Brønsted acid catalysts, diphenylphosphate (20 mol %) was identified as a suitable catalyst for the reaction. Toluene again

• (Scheme 4). A plausible mechanism was suggested by the authors and is shown in Scheme 5. Initially, the vinylogous iminium (azafulvenium) ion 5 is formed from the acid-catalyzed dehydration reaction of tertiary aminobenzaldehyde and indole (Scheme 5). Subsequently, 5 undergoes a 1,5-hydride shift to

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• 1,2-hydride shift to intermediate 27 followed by elimination of the metal catalyst [25] to afford the observed cyclopropane product 6. An alternative reaction pathway may be invoked for the ethyl-substituted substrate 22 leading to product 23 (Scheme 4). After initial cyclization of the enol ether

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

• migration of R3 are strictly limited to compounds that bear a quaternary center (R3 = alkyl, R2 ≠ H). As shown for the gold(I)-catalyzed reaction of 1,5-enyne 53, the formation of the bicyclo[3.1.0]hexene 54 is driven by the release of ring strain. Enynes with R3 = H undergo exclusively a hydride shift to

Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

• Paul W. Davies,
• Nicolas Martin and
• Neil Spencer

Beilstein J. Org. Chem. 2011, 7, 839–846, doi:10.3762/bjoc.7.96

• 1,2-aryl shift in preference to either proton elimination or a 1,2-hydride shift. We therefore sought to validate this proposal experimentally by isotopic labelling. Results and Discussion A deuterium labelled precursor Alkynyl aziridine 4 was selected as the initial probe for the mechanism which

Molecular rearrangements of superelectrophiles

• Douglas A. Klumpp

Beilstein J. Org. Chem. 2011, 7, 346–363, doi:10.3762/bjoc.7.45

• superelectrophile, which undergoes rearrangement via the protonated cyclopropyl derivative 49. Final reaction steps include a hydride shift and deprotonations to give 50. Jacquesy and coworkers [24] have investigated the chemistry of polycyclic ketones in HF-SbF5-CCl4, a powerful reagent combination for

• hydride migration in 70 to give dication 71. This step should be favorable because it increases the distance between charge centers. Although a hydride shift is the most direct route from 70 to 71, this isomerization may also occur through deprotonation and reprotonation steps. As noted by the authors of

• -diprotonated species 93. Migration of the methyl group leads to separation of the charge centers and the formation of dication 94. Theoretical calculations show that hydride shift for the dications (94 → 95) is energetically unfavorable, presumably due to the closer proximity of the charges. In the final steps

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans – an approach to carbohydrate mimetics

• Fabian Pfrengle and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 75, doi:10.3762/bjoc.6.75

•  10). Sodium azide presumably acts as base to initiate the reaction by deprotonation of the hydroxylamine moiety. A hydride shift from the benzylic position to the 3-position of the pyran ring produces the nitrone moiety of 21 and simultaneously displaces the axially positioned bromo substituent by an

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• intermediate which subsequently undergoes an intramolecular [1,3]- or [1,5]-hydride shift resulting in the desired diarylmethanes 9 in good yields. Electron donating and electron withdrawing functional groups of aldehyde moiety are tolerated in this reductive Friedel–Crafts alkylation procedure. However, there

• is no clear correlation between the electron deficiency of the arenecarbaldehyde and the reaction yield [4]. Further mechanistic investigations were performed with 1,3-propanediol-1,1,3,3-d4 in order to provide more information about the observed hydride shift. Indeed deuterium was incorporated into

Diastereoselective functionalisation of benzo-annulated bicyclic sultams: Application for the synthesis of cis-2,4-diarylpyrrolidines

• Susan Kelleher,
• Pierre-Yves Quesne and
• Paul Evans

Beilstein J. Org. Chem. 2009, 5, No. 69, doi:10.3762/bjoc.5.69

• carbocation rearrangement takes place faster than any nucleophilic interception of species 21 and 22. (A hydride shift from the bridging CH2 to carbocation 21 was also considered; however, based on the regioselective formation of compound 19b this mechanism was discounted.) The remarkable contrasting