Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• of a reducing agent (NaBH(OAc)3). The preferential formation of 11 relative to imine reduction, even in the presence of an excess of reducing agent, suggests a rapid intramolecular rearrangement of an iminium derivative 12 to the highly activated ortho-position of the aromatic ring. The possible

Solvent-free sonochemistry: Sonochemical organic synthesis in the absence of a liquid medium

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 1850–1856, doi:10.3762/bjoc.13.179

• minutes of ultrasonic irradiation a bright orange free flowing solid was produced indicating that a reaction had occurred. 1H NMR spectroscopy showed that indeed a reaction had taken place to form the desired imine; however, a conversion to product of only 69% was determined. The experiment was repeated

• sonicated for 60 minutes to produce a dark red solid (similar to that obtained from solution). 1H NMR spectroscopy indicated that the reagents had almost all been consumed; however, it was noted that the 1H NMR spectrum was more complicated than expected with two peaks representing imine protons. It was

• ). Powder X-ray diffraction (PXRD) analysis shows that the powder patterns of both the sonochemical product and the solution product are the same and IR spectroscopy confirmed that an imine bond was present in the product, with no indication of an aldehyde functionality being present (see Supporting

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• SET mechanism to generate a radical cation B, followed by fragmentation to afford 12 (Scheme 3b). Either of these processes provided the imine moiety, along with o-iodosobenzoic acid (IBA, Scheme 3). In general, IBX-mediated oxidative dehydrogenation is conducted at high temperatures (>50 °C

• substituted 2-aminophenol (Scheme 38). Accordingly the reaction is believed to have initiated by the formation of imine intermediate V. The 4-methoxy-TEMPO radical interacted with V and subsequent H-absorption from the phenol moiety afforded phenoxy radical W and 4-methoxy-TEMPOH which gets re-oxidized to the

• 4-methoxy-TEMPO radical by oxygen. W gets stabilized by the imine moiety to form the corresponding amine radical X′′. The second hydrogen abstraction between X′′ and 4-methoxy TEMPO/oxygen facilitates the aromatization to afford the desired compounds (Scheme 38). In another example 4-hydroxy-TEMPO

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• substantial degree of steric encumbrance has been prepared via a novel variant of the Castagnoli–Cushman reaction of homophthalic anhydride (HPA) and various indolenines. The employment of a special kind of a cyclic imine component reaction allowed, for the first time, isolating a Mannich-type adduct between

• HPA and an imine component which has been postulated but never obtained in similar reactions. Keywords: Castagnoli–Cushman reaction; diastereoselectivity; homophthalic anhydride; indolenines; lactam synthesis; multicomponent reactions; Introduction The reaction of imines (prepared in a separate step

• ) N-acylation of the imine component followed by intramolecular Mannich reaction or (b) Mannich-type addition of the HPA enolate to a protonated imine component followed by intramolecular aminolysis of the cyclic anhydride moiety in Mannich adduct 13 (Scheme 3) [1]. Investigation of the CCR leading to

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• products 22 and 23 [24] (Scheme 3). The proposed mechanism was based on the isolation of the 4-nitrodiaminobenzene imine intermediate which possessed reduced reactivity for intramolecular cyclisation. This type of reaction was exploited in the literature several times for the synthesis of quinoxalin-2(1H

• standardized conditions: DMF, rt, 3 days (General procedure A). In all cases, the most nucleophilic amine from diamine 11 predominantly reacts with the most reactive α-carbonyl group from ester 12a to form an imine/enamine bond followed by amidic intramolecular cyclization to yield the main regioisomer of 3,4

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• practical synthetic methods for the selective synthesis of precursor dialkynes bearing different substituents (alkyl, aryl) at the triple bonds, based on ketals or an imine as protecting groups. We show for isomeric dialkynes that the reaction cascade induced by Pt(II) includes ring annulation, sulphur

• shift in compound 15, where the alkynyl substituent is nearby. As an alternative to the introduction of an acetal, an imine was tested for its suitability as a protecting group for the carbonyl moiety, as shown in Scheme 6. 3-Oxocamphorsulfonylimine 3 was converted into the imine 19 by reaction with 2

• ]. When two equivalents of the acetylide are used, the reaction still produces 20 only, and no reaction at the 3-position in the imine was observed. The high selectivity of this reaction can be explained by the large difference between the electron-deficient sulfonylimine and the electron-rich imine. The

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• reaction towards the imine product [20]. Attempts to conduct this reaction on acidic conditions failed as in other glycamines synthesis [19]. Experiment outlined in Table 1, entry 1, using ammonium hydroxide as ammonia source resulted in a complex mixture with no evidence of amine 3 formation. Reaction

• see Supporting Information File 1. We could access pure 8 by reacting 7 and formaldehyde under reductive conditions. The reaction product 8 kept the original configuration of its parenting analogue, amine 7, because the reaction between such primary amine 7 and formaldehyde occurs via an imine

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• corresponding aldehyde by passing it through a packed column containing tetra-N-alkylammonium perruthenate (10 equiv) at room temperature to achieve quantitative yield. Further, these two products are reacted with each other to get the imine intermediate. The catch and flow technique is used with polymer

• -supported phosphine (20 equiv) as the trapping agent. The imine is further hydrogenated at 25 °C and 20 bar pressure by using an H-cube reactor with 10% Pd/C as a catalyst [72]. Trifluoroacetylation of the amine intermediate is then carried out in a chip reactor with trifluoroacetic anhydride (in DCM) as a

• packed bed reactor control strategy will remain identical for all reagent packed reactors. The azide and the aldehyde intermediate can be mixed and preheated at the reaction temperature and passed through a phosphine-functionalized polymer packed bed reactor to obtain the imine intermediate. This imine

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• resonating at 5.28 ppm showed strong correlations with the imine carbon atom, the ipso-carbon atom and two α-carbon atoms of the pyrrole ring, clearly indicating that the methylene group is incorporated into the seven-membered ring. All this information shows that the methylene group is located between the

• pyrrole ring and the imine double bond. With these encouraging results in hand, we embarked on the evaluation of the substrate scope for this useful transformation. The compounds 7a, 7b, and 7d were submitted to a cyclization reaction under the same reaction conditions applied to compound 7c. As shown in

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• through a GBB reaction/cyclization strategy (Scheme 1). The intermediate GBB product 4a could be constructed starting from 2-ethynylbenzaldehyde (2a) through an imine formation/formal [4 + 1] cycloaddition/[1,3]-H shift. The so obtained GBB product imidazo[1,2-a]pyridine 4a bearing an amino group and an

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• formation [12][13][14], Diels–Alder reaction [15][16] or the imine/oxime condensation [17][18]. These reactions tend to produce strong covalent interactions between the surface and the molecules in solution which ensure a stable immobilization. One limitation of the covalent strategy lies in the

• functionalization or the ability to tune the properties of SAMs by controlled spatial functionalization. A scant number of examples have reported reversible covalent reactions on SAMs on gold surfaces; for instance, Ravoo and Reinhoudt have described the formation of imine SAMs prepared by reaction of an amino

• for the formation of aromatic mixed self-assembled monolayers containing both imine functionalities and protonated anilines on the surface [20]. In order to bring a new class of reusable surfaces, we describe herein the use of sulfamide chemistry for the generation of reversible patterns of sulfur

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• . The homoallylic amine 1 with syn-configuration was obtained by the reaction of the corresponding imine with allylmagnesium bromide as previously described [15]. The amine 1 was reacted with the Schwartz reagent in CH2Cl2 at room temperature to afford the hydrozirconated intermediate, which was

• 52% overall yield starting from homoallylic amine 3 having anti-configuration, which was obtained by reaction of the corresponding BF3·OEt2 pre-complexed imine with allylmagnesium bromide as previously described [15] (Scheme 2). It is worth mentioning that the starting homoallylic amines 1 and 3 can

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• mentioned above, a two-step protocol – conversion of 1 into N,N’,N’’-tris(benzylideneamino)guanidinium chloride followed by catalytic hydrogenation of the imine groups – was developed. The fluorophenyl-substituted salt 5 was prepared analogously. Depending on the reaction conditions, the guanidinium salts 4

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• ], mercury [26], cobalt [27], iridium [28], ruthenium [29], indium [30] etc. Other methods towards the synthesis of propargylamine include: alkynylation of imine [31][32][33], enamine [34], and Csp³–H bonds adjacent to N-atoms [35][36]. In the A3 coupling, the role of the metal catalyst is believed to

• . Furthermore, reactions with primary amines like cyclohexylamine and benzylamine produce only the imine and no A3-coupled product, signifying that imines are less efficient than iminium species to initiate further reaction with terminal alkyne. Conclusion In conclusion, the present study demonstrates an

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• , this compound polymerizes rapidly even at low temperatures, such as −50 °C. Therefore, until 1989 abicoviromycin (168) has not been successfully synthesized. The unit which probably determines the reactivity and unstability of abicoviromycin (168) is the diene-imine fragment. Due this fact, the authors

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• corresponding free amines. Such desulfonylation of sulfonamides has been less utilized to make an unsaturated bond, for example, imine. Hence, attention has been paid to find suitable conditions for the formation of pyrazinones directly from piperazine-2,6-diones via cyclization followed by dehydrosulfonylation

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• ][16][17][18][19]. The coupling of alcohols and amines is made possible by the catalysts ability to take two H atoms from the alcohol, oxidising it to an aldehyde. The aldehyde then reacts with the amine affording an imine, which is subsequently reduced by transferring two H atoms back from the

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• to analyze NMR (via Labview software) data and optimize the reaction conditions. They performed a range of reactions including imine formation (Figure 14), electrophilic fluorinations and Diels–Alder reactions. This system was employed to perform kinetic studies, in-line structural characterization

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• hydride donors (Scheme 6). Alternatively, secondary amines could involve an elimination of HCN and reduction of the formed imine. NaBH4 [45][46][47][48][49][50][51] or NaBH3CN [47][52][53][54][55][56][57][58][59] are widely used hydride donors and, less frequently, BH3 [60][61], AgBF4/Zn(BH4)2 [62][63][64

• NaBH4. The resulting imine 21 is reduced by BH3 with the help of the cyanoborohydride anion. The formed anion 22 abstracts a proton from complex 20 to produce 23 or 24 and regenerate 21 and BH3CN−. A set of experiments supports this proposal. Notably, borane is the major hydride source for the reduction

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• reaction mechanism involves a nucleophilic attack on the ester carbonyl, which leads to the formation of an amide intermediate. This means that the amidine does not attack the (more reactive) ketone carbonyl as expected, which would lead to an intermediate imine. Since the more reactive center of the

• of the site. Knowing that the formation of imine and amide intermediates in this reaction proceeds through the elimination of one water and one ethanol molecule as cleavage products, direct energetic comparisons were performed between each intermediate/cleavage product pair. The DFT-B3LYP calculation

• method showed that the amide/ethanol pair are by −8.33 kcal·mol−1 and −6.79 kcal·mol−1 more stable than the imine/water pair for the ethylenediamine and acetamidine derivatives, respectively (Table 10). These results, which are in agreement with the experimental results obtained for the reaction between

Spectral and DFT studies of anion bound organic receptors: Time dependent studies and logic gate applications

• Srikala Pangannaya,
• Neethu Padinchare Purayil,
• Shweta Dabhi,
• Venu Mankad,
• Prafulla K. Jha,
• Satyam Shinde and
• Darshak R. Trivedi

Beilstein J. Org. Chem. 2017, 13, 222–238, doi:10.3762/bjoc.13.25

• position of the imine linkage connecting the conjugated naphthyl group. The pyridine ring possessing –CN and –NO2 functionalities in R1 and R2 reflect their identity as a signaling unit/chromophore. In total, the nature and position of binding site and signaling unit play the key role in the chromogenic

• the imine nitrogen [41][42][43]. The proton corresponding to the OH group centered at 14.8 ppm (R1) and 14.78 ppm (R2) exhibited a strong hydrogen bond with AcO− ion indicated by the signal broadening upon successive addition of 0.5 and 1 equiv of the anion. In the presence of 2 equiv AcO− ion, the

• proton signal diminished indicating deprotonation. The imine proton did not exhibit an upfield or downfield shift, yet the signal intensity decreased upon successive addition indicative of its involvement in the bifurcated hydrogen bond interaction with the AcO− ion. The aromatic protons in R1 and R2

Highly bulky and stable geometry-constrained iminopyridines: Synthesis, structure and application in Pd-catalyzed Suzuki coupling of aryl chlorides

• Yi Lai,
• Zhijian Zong,
• Yujie Tang,
• Weimin Mo,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen,
• Liqun Jin,
• Wen-hua Sun and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 213–221, doi:10.3762/bjoc.13.24

• reactions with the advantage of convenient synthetic methods, easy functional group modifications and better stability [37][38][39][40][41][42][43]. Pyridine, azole and imine-based N(sp2) ligands received considerable attention, especially bidentate N,N-ligands. In general, most bidentate N,N(sp2) ligands

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• preparation of new derivatives. Results and Discussion Synthesis of α-aryl-α-aminophosphonates and α-aminophosphine oxides At first, the imine starting materials 1 were prepared by the condensation of benzaldehyde and its chloro-substituted derivatives with primary amines, such as butyl-, cyclohexylamine or

• (Table 1). The products were α-aminophosphonates 2a–d and α-aminophosphine oxide 2e. The addition of 1 equivalent of dimethyl phosphite (DMP) to imine 1a at 80 °C was almost complete after 30 min, and dimethyl ((butylamino)(phenyl)methyl)phosphonate (2a) could be isolated in a yield of 73% (Table 1

• conditions, the reaction of dibenzyl phosphite (DBnP) was also clear-cut and afforded dibenzyl ((butylamino)(phenyl)methyl)phosphonate (2d) in 69% yield (Table 1, entry 10). Finally, diphenylphosphine oxide (DPPO) was added to imine 1a. After 10 min irradiation at 100 °C, complete conversion was observed and

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• one of the first examples of utilizing tetralkylammonium salts as hydrogen bond donor catalysts, the authors provided no mechanistic proposal for the catalytic activity of L7–L10, and the activation of the imine by the formation of a C–H···N hydrogen bond was proposed later by Maruoka and Shirakawa

• directionality that might make these interactions of a great value to the field of organocatalysis [71][72][73]. Molecular iodine has been used for many decades as a mild catalyst or promoter of various organic transformations such as conjugate addition, imine formation or aldolate dehydration reactions [74][75

• bond-donor activation of α,β-unsaturated carbonyl compounds in the [2 + 4] cycloaddition reaction of MVK and cyclopentadiene [88]. Halogen bond donor activation of imines in the [2 + 4] cycloaddition reaction of imine and Danishefsky’s diene [90]. Transfer hydrogenation catalyzed by a chiral halogen

Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• focus of this review [5][6][7][8]. Additionally, analogous catalytic aza-Wittig reactions, in which carbon–nitrogen double bonds of imine groups are formed, will also be discussed in the second section of this review. Review Catalytic Wittig reactions A key requirement for versions of the Wittig

• reactions in that they also involve the reaction of a phosphonium ylide, in this case an iminophosphorane (or phosphinimide) such as 39, with a carbonyl group containing compound to form the carbon–nitrogen double bond of an imine along with a byproduct phosphine oxide such as 2 (Scheme 12). The difference