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

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• our ongoing investigation of the role of titanium salts in mediating selective radical transformations [13][14], we have developed new, simple protocols for the synthesis of complex organic compounds through nucleophilic radical addition to imines generated in situ [15]. Several recent contributions

• approach. In fact, our procedure requires neither the preformation of imines nor anhydrous media, due to the coordinating effect of titanium salts, which promote the one-pot synthesis of amino derivatives according to a classical MCR. The basic approach consists of the simple mixing of an aniline, an

• imines through a ring opening of the ether (Scheme 2, entry c) [30]. Even though it is interesting by itself, this domino reaction limits the general approach towards the synthesis of a wider range of β-amino-alcohols and ethers. The importance of these derivatives is well-documented. They are the key

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• coupling of an activated alkene with an electrophile (usually aldehydes or imines) in the presence of a catalyst (Figure 1). The reaction is organocatalytic, atomically economical and operationally simple in nature. Most importantly, it results in the synthesis of densely functionalized molecules, also

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

• 1980s, Leardini et al. [15] have shown that under radical conditions via a homolytic aromatic substitution route diaryl-imines were suitable precursors to a number of 6-arylphenanthridine derivatives. The reaction proceeded by initial imidoyl-H atom abstraction by the electrophilic iPrO• radical, and

• rapid rearomatization with the loss of HPdSePh to give the phenanthridine. Candito et al. reported a new and highly efficient method for the synthesis of variously substituted phenanthridine derivatives employing N-unsubstituted imines or N-silylimines [33]. The method is limited to ortho-substituted

• preparation from easily available starting material (benzylamine, aryl iodide, imines, etc.) in few reaction steps, under mild reaction conditions and with yields within the 50–90% range. The great advantage of this approach is the very broad versatility in preparation of phenanthridine derivatives, poly

A novel 4-aminoantipyrine-Pd(II) complex catalyzes Suzuki–Miyaura cross-coupling reactions of aryl halides

• Claudia A. Contreras-Celedón,
• Darío Mendoza-Rayo,
• José A. Rincón-Medina and
• Luis Chacón-García

Beilstein J. Org. Chem. 2014, 10, 2821–2826, doi:10.3762/bjoc.10.299

• develop a stable and efficient Pd catalyst for these reactions. Recently, palladium complexes containing imidazole-imines [12], binary nanoclusters [13], N-heterocyclic carbenes (NHCs) [14], nanoparticles [15], palladacycles [16], and Schiff bases [17] have been developed as highly effective phosphine

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• -3,4’-pyridine] derivatives can be synthesized by employing other nitrogen-containing nucleophiles such as hydrazine and imines in the similar four-component reactions. In fact, the four-component reaction of hydrazine, acetylenedicarboxylate, isatin and malononitrile for the formation of spiro

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• and lead to a decrease in faradaic efficiency. Electrocarboxylation, the electrochemical fixation of carbon dioxide in organic chemicals, involves the electroreduction of carbon dioxide and/or an organic substrate. For olefins, alkynes, carbonyl compounds, imines and organic halides, this leads to the

• , like activated olefins, imines, carbonyl and halogen compounds, and other anions like an azide, which forms inert N2 upon oxidation [52]. Eventually the electrocarboxylation of 1,3-butadiene was also conducted with sacrificial anodes, resulting in a high selectivity for the C6 product (Table 1, entries

• , aldehydes and imines As is the case for conjugated dienes, olefins and alkynes, two possible pathways exist for electrocarboxylation of carbonyl and imine compounds. One starts with CO2 reduction; another starts with reduction of the substrate (Scheme 11). The second route is considered as the predominant

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• ) measured with C18-UPLC–ESIMS using a linear gradient of solvents A (water/acetonitrile/formic acid 98:2:0.1; v/v/v) and B (acetonitrile/0.1% formic acid; v/v) and solvent composition and masses of imines 11–14 formed in a model reaction between L-lysine and DDY (10) followed by CuAAC with the different

Oxidative phenylamination of 5-substituted 1-hydroxynaphthalenes to N-phenyl-1,4-naphthoquinone monoimines by air and light “on water”

• Julio Benites,
• Juan Meléndez,
• Cynthia Estela,
• David Ríos,
• Luis Espinoza,
• Iván Brito and
• Jaime A. Valderrama

Beilstein J. Org. Chem. 2014, 10, 2448–2452, doi:10.3762/bjoc.10.255

• unexpected but interesting result indicates that on-water oxidative amination reaction of 1,5-DHN (1) with 4-hydroxyphenylamine to produce compound 6 is more favorable than the photooxygenation reaction to give juglone (2). The N-phenylquinone imines are considered as an important class of compounds because

• substitution at the 4-position of compound 1 followed by oxidation of the aminonaphthol intermediate, yield the N-phenyl-1,4-naphthoquinone-4-imines. A mechanism involving radical cation intermediates is supported by the rather high product yields resulting from the reaction of 1,5-DHN (1) with electron-donor

Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

• Jan Szabo,
• Kerstin Karger,
• Nicolas Bucher and
• Gerhard Maas

Beilstein J. Org. Chem. 2014, 10, 2255–2262, doi:10.3762/bjoc.10.234

• was combined with benzaldehyde and hydratropic aldehyde to furnish the corresponding tris(imines), which were converted into 1,2,3-tris(benzylamino)guanidinium salts by catalytic hydrogenation in the former, and by borane reduction in the latter case. The resulting alkyl-substituted

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• phosphines possessing various chiral skeletons that have been used in asymmetric nucleophilic organocatalytic reactions, including annulations of allenes, alkynes, and Morita–Baylis–Hillman (MBH) acetates, carbonates, and ketenes with activated alkenes and imines, allylic substitutions of MBH acetates and

• developments in nucleophilic chiral phosphine-catalyzed asymmetric reactions, including annulations of allenes, ketenes, alkynes, and Morita–Baylis–Hillman (MBH) carbonates with activated alkenes and imines, allylic substitution of MBH acetates and carbonates, Michael additions, γ-umpolung additions, and

• developed, asymmetric variants exist for only a few of them. In particular, chiral phosphine-catalyzed [3 + 2] annulations of allenes, alkynes, and MBH adducts with electron-deficient olefins and imines, resulting in cyclopentenes and pyrrolidines, have been the most studied, with many successful reported

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

• synthesis of MMP-inhibitors [63], as discussed later in this review. Aziridines are also obtained as primary products in the addition of chloromethyl phosphonamide 28d to imines. The initial attack leads to a α-chloro-β-amino phosphonamide adduct as intermediate, which then undergoes intramolecular

• cyclization to form the aziridine ring after elimination of chloride. When N-substituted aromatic imines are used, the corresponding aziridines can be reduced at the benzylic carbon to give α-aminophosphonic acids [64]. Synthesis of phosphonamides There are four major methods for the synthesis of

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• cyclic dipeptide [5]. In these reactions, N-substituted imines react with HCN to yield (S)-α-aminonitriles with remarkably high enantiomeric excess (ee). One example is shown in Scheme 3. However, when benzaldehyde and NH3 instead of the N-substituted imine were employed as the substrates, the reaction

• afforded an initial product Ph-CH(NH2)-CN of configurational instability[5]. In the following, Sigman and Jacobsen used a parallel combinatorial library synthesis for the discovery and optimization of a chiral catalyst for the reaction of imines and HCN [6]. From then on, various catalytic asymmetric

• Strecker reactions have been reported to gain high enantioselectivity of the hydrocyanation reaction of imines [7][8][9][10][11][12]. However, the origin of the enantioselectivity in the asymmetric Strecker reactions has not been clarified. To our knowledge, the elementary processes of the whole Strecker

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• Braunschweig, Germany 10.3762/bjoc.10.150 Abstract A facile route towards highly functionalized 3(2H)-furanones via a sequential Mannich addition–palladium catalyzed ring closing has been elaborated. The reaction of 4-chloroacetoacetate esters with imines derived from aliphatic and aromatic aldehydes under

• closure of the primary adduct to form the furanone. In this paper, we report our investigations that extend the reaction to heteroatom-containing electrophiles such as imines and diazo esters. Results and Discussion Following the work on nitrostyrenes, Yan et al. also reported a two-step asymmetric route

• towards 4-substituted-furanones from imines [41]. Recently Fructos et al. have shown that N-p-toluenesulfonyl-protected imines were better candidates for gold catalyzed Mannich addition of acetoacetates when compared to N-Boc (tert-butoxycarbonyl) and N-PMP (p-methoxyphenyl) imines [42]. Hence, we

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

• Gadi Ranjith Kumar,
• Yalla Kiran Kumar,
• Ruchir Kant and
• Maddi Sridhar Reddy

Beilstein J. Org. Chem. 2014, 10, 1255–1260, doi:10.3762/bjoc.10.125

• groups (including the discoverers) have utilized the reaction for the synthesis of diverse chemical compounds by trapping the thus formed ketenimine inter- and intramolecularly. Various multicomponent reactions using external nucleophiles like H2O, alcohols, amines, imines, etc., have been reported while

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• contrast to that, photochemical redox activation is possible in the presence of titanium(IV) catalysts [19][20][21][22]. As shown in a series of papers by Sato and coworkers, carbonyl compounds 1 as well as imines couple with methanol to give the 1,2-diols or 1,2-amino alcohols, respectively, when

• solutions is cumbersome and it is unclear what species is catalytically active. These processes have thermal counterparts in reduced titanium-mediated chemistry, e.g., the Ti(III)/t-BuOOH-mediated hydroxymethylation of imines [23][24]. In order to evaluate the nature of the active catalytic species in the

• under lower concentration of the acceptor ketone and the probability of hydroxybenzyl radical dimerization (i.e., route II) is disfavoured under these conditions. Photohydroxymethylation of carbonyl compounds and imines. Model process: photocatalyzed acetophenone/methanol reaction. Photocatalyzed

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• -ylidenes spontaneously dimerize under ring cleavage of one of the N,N-bonds and ring closure to an indazole–indole spiro compound which possesses an exocyclic imine group. The E/Z isomers of the imines can be separated by column chromatography when methanol is used as eluent. We present results of a single

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• , benzene (PCM)), respectively, that far exceed the barriers to reactions leading to compound 3. These do not allow the possibility that azomethine ylide 10 can be a probable intermediate in the formation of adducts 4 and 5. It has been known that imines react with acylketenes, generated from furandiones

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• substrate scope for the borylation reaction, several other new N-phosphinyl imines were synthesized for examination (Scheme 3). Ti(OiPr)4 was chosen as the general condensation reagent. When aliphatic aldehydes were subjected to the condensation reaction, the main products were generated either as

• hemiaminals 7 or as a mixture of imine and hemiaminal after purification by column chromatography. The hemiaminals were slowly transferred to the corresponding N-phosphinylimine as revealed by NMR analysis. The aliphatic imines are found to be unstable even in the presence of a trace amount of moisture, and

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• synthesis of chiral bicyclic phosphinates 23a–k by domino hydrophosphinylation/Michael/Michael reaction was realized by Fourgeaud et al. (Scheme 10) [25]. Several 1-oxa-3-aza-6-phosphabicyclo[3.3.0]octanes derivatives 23a–k were obtained in yields around 70% by reacting allenes 21 with imines 22 derived

• -chloropropyl-H-phosphinate 33 with imines 34 in toluene at reflux (Scheme 14) [29]. 1,3-Azaphosphindoles and 1,3-benzazaphosphorines Several compounds in this series were synthesized by Montchamp and coworkers using two different approaches. The first one is the reaction between an imine 34 and 2-bromophenyl

• [23][36]. This versatile intermediate 59 was reacted with aldehydes, imines, olefins and aryl bromides or aryl iodides to generate a wide range of phosphinates. The same authors have also prepared another H-phosphinate intermediate 61 in 71% yield (Scheme 25) [37]. This oxazaphosphinane 61 was

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• ][39]. Recently, our groups have developed a new type of chiral phosphonyl auxiliaries for imines [40][41][42][43][44]. Compared with the reported sulfinyl auxiliaries (Figure 1a) [45][46][47][48], the phosphonyl ones exhibited advantages in the concise preparation method from readily available

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• , several cyclization strategies have been utilized in order to obtain cyclic constructs. For example, the incorporation of cyclic imines immediately gives cyclic MCR-products, whereas other strategies make use of unreactive, convertible or protected functional Ugi-substrates that can be cyclized via

• - [31], elastase- [32][33][34][35], and HIV-1 protease [36] and papain [37]. For the design of β-lactams, the Staudinger reaction involving a [2 + 2] cycloaddition of ketenes and imines is the most common method used [38]. However, Ugi reactions starting form β-amino acids are also described. In 2002

• %). In addition, the mild conditions tolerate a wide range of Ugi-substrates, resulting in a broad range of different pyrrolidine mimics 32. A more straightforward method [53] includes a single Joullié-Ugi 3CR using previously described alkyl substituted cyclic imines [54] giving the cyclic constraint

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

• -coupling products into tandem reactions. The second goal could be achieved by classifying reactions on the basis of the involved reactants, the reaction type or the role of the catalyst. Review A3-coupling-type reactions Silver catalysis The catalytic direct 1,2-addition of alkynes to imines and iminium

• related cascade multicomponent processes of interest, which involve gold acetylides and imines. Among them, a new Au(I)-catalyzed entry to cyclic carbamimidates 17 starting from acetylenes, imines and p-toluenesulfonylisocyanate (18) was reported by Toste and Campbell [43]. The reaction gave mainly the 5

• partners, but imines bearing hindered ortho substituents or too electron-rich imines were not allowed. The reaction with alkylacetylenes( i.e., 1-hexyne), resulted in low yields and selectivity (Scheme 13). The proposed mechanism is shown in Scheme 14. The coordination of acetylene to gold produces the

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

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

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• -supported benzotriazole [7] with arylmagnesium reagents, addition of phenyllithium to selenoamides [8], addition of organometallic species [9][10][11][12][13][14][15][16][17][18][19][20][21] or arylboronic acids [22][23][24][25][26][27] to imines, reaction of organolithium and Grignard reagents with

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• /imines [13][14][15] and isocyanides [16][17]. Experimental Typical procedure for the synthesis of dihydrobenzoxazepinones 10a–n. A solution of benzyl azide 2 (1 mmol) in dry THF (3 mL) was treated with trimethylphosphine (1 M solution in toluene, 1.1 mmol) and stirred for 2 h at room temperature. Then