Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• alkenylation reaction of pivalophenone N–H imine with an alkenyl phosphate. The reaction tolerates various substituted pivalophenone N–H imines as well as cyclic and acyclic alkenyl phosphates. Keywords: alkenylation; C–C bond formation; C–H activation; cobalt; imine; Introduction Transition-metal-catalyzed

• catalyst, which is reported herein (Scheme 1c). The present alkenylation features a mild reaction temperature and displays applicability to a variety of substituted pivalophenone N–H imines and alkenyl phosphates. It should be emphasized that pivalophenone N–H imines and related bulky N–H imines can be

• readily prepared from the corresponding aryl nitriles and organolithium or Grignard reagents, while analogous N-substituted imines are nontrivial to synthesize because of sluggish ketone/amine condensation. As such, the present reaction would complement the N-arylimine-directed alkenylation. Results and

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• at 78 °C, [4 + 2] cycloaddition took place between the o-QM generated from the corresponding aminonaphthol as diene component and cyclic imines playing the role of heterodienophiles (Scheme 5). Fülöp and co-workers then extended their studies by applying both 2-aminoalkyl-1-naphthols and 1-aminoalkyl

• -2-naphthols [81]. These bifunctional compounds were reacted with various cyclic imines such as 4,5-dihydrobenzo[c]azepine or 6,7-dihydrothieno[3,2-c]pyridine to have new naphthoxazinobenzazepine 44 and -thienopyridine 45 derivatives [82]. Transformations at 80 °C in 1,4-dioxane as solvent were

• polyheterocycles formed was also described. The [4 + 2] cycloadditions between cyclic imines and o-QMs derived from Mannich bases could also be successfully applied in the syntheses of natural alkaloid-like compounds 47. Osyanin et al. reported the preparation of rutaecarpine and evodiamine, the 14-oxa analogues

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• fashion leading to cyclic as well as acyclic products, and includes (aza)-versions using imines instead of aldehydes or ketones as electrophilic partners. In addition, the mild reaction conditions usually employed and the use of cheap nontoxic metals has prompted the development of diastereo- and

• -β-(N-tert-butylsulfinyl) amino esters through ZnEt2-mediated aza-Reformatsky reactions of the corresponding chiral α-oxygenated sulfinyl imines 25 with ethyl bromodifluoroacetate (26) performed in the presence of RhCl(PPh3)3 as an additive in THF [27]. Starting from (S)-N-tert-butylsulfinyl imines

• 25, the reaction led to the corresponding (R,S)-products 27 as major diastereomers in low to excellent diastereoselectivities (6–90% de) and moderate yields (46–64%). The lowest diastereoselectivity (6% de) was obtained in the reaction of aliphatic sulfinyl imines (S)-25a,b (R = Et, C11H23) while

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• synthetic versatility of quinone-catalyzed oxidative C–C bond cleavage. Keywords: catalysis; deformylation; organic synthesis; organocatalysis; Introduction Imines are extremely versatile intermediates in organic chemistry [1][2][3]. Consequently, many synthetic methods have been developed for the

• preparation of imines (Scheme 1). The condensation of an amine with an aldehyde or ketone is the oldest and most commonly employed method for imine synthesis [4]. More recently, the catalytic dehydrogenation of amines mediated by metal and organic catalysts has begun to emerge as an alternative approach for

• the preparation of imines [5][6]. The majority of these methods involve cleavage of a C−H bond at the α-position of an amine substrate [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Methods that deliver imines through amine α-C−C bond cleavage are far less

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• decarboxylative addition of malonic acid mono(thio)esters to aldehydes and imines has become an increasingly popular synthetic strategy [28][30][31][32][33][34][35][36]. However, the utility of trifluoromethylketimines as electrophilic substrates in this reaction remains underinvestigated. The only published work

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• domino reactions of diazo compounds with intermediate formation of ylides [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Thus, it was for example shown that ammonium or oxonium ylides generated in the course of intermolecular processes can be easily trapped by ketones, imines, α,β-unsaturated

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• , Nakanarusawa 4-12-1, Hitachi 316-8511, Japan 10.3762/bjoc.13.244 Abstract As an extension of the boron enolate-based aldol reactions, the oxazolidinone-installed bisimide 1a from 3-(trifluoromethyl)glutaric acid was employed for Mannich reactions with tosylated imines 2 as electrophiles to successfully obtain

• article. Results and Discussion On the basis of our previous study [4], the chiral glutarimide 1a was employed as the starting material and optimization of reaction conditions with benzaldehyde-based imines 2 was performed (Table 1). Lithium enolate by the action of LDA to 1a was found to be ineffective

• as long as the imines with benzyl (2aa) or Boc (2ab) as substituents R were employed (Table 1, entries 1 and 2). However, the attachment of the stronger electron-withdrawing 4-toluenesulfonyl (Ts) moiety attained efficient activation of the imine 2ac to afford the desired Mannich product 3a in 85

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• substituents in the Cα-position facilitate a base induced rearrangement to α,β-unsaturated imines, while azide-substituted propargylamines form triazoles under surprisingly mild conditions. A panel of propargylamines bearing fluoro or chloro substituents, polar functional groups, or basic and acidic functional

• groups is accessible for the use as precursors of peptidomimetics. Keywords: amino acid analogous side chains; desilylation; Ellman’s chiral sulfinamide; intramolecular Huisgen reaction; peptidomimetics; propargylamines; rearrangement to α,β-unsaturated imines; Introduction Terminal alkynes display an

• structure of fluorinated propargylamines occurs in important drugs, like HIV protease inhibitor DPC 961 and its analogues [78][79][80][81][82][83], particular effort was put on the synthesis of N-sulfinyl propargylamine 7k. Because of the poor electrophilicity of imines 5, the nucleophilic addition of

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• spirocyclization via conversion of 1,3-diones 8 into mono-hydrazones. Indeed, while mono-imines of these ketones strongly prefer keto-enamine tautomeric form 13 over enol-imine form 14 (Scheme 4) [44][45], the corresponding hydrazones have been reported to favor enol-hydrazone tautomer 16 (Scheme 4) [46][47][48

• -catalyzed spirocyclization of enoles (vinylogous carbonates and carbamates) with 5-methoxycarbonyl-1H-pyrrolediones. Acid-catalyzed spirocyclization of enoles (vinylogous carboxylates) with 5-alkoxycarbonyl-1H-pyrrolediones. Formation of mono-imines and mono-hydrazones of 1,3-cyclohexanediones and

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• the sole products. Contrastingly, in the solution of acetonitrile imines of benzaldehyde and amines were formed preferably. Different aromatic or heteroaromatic aldehydes including thiophene carboxaldehyde, pyridine carboxaldehyde and cyclohexyl carboxaldehyde as well as various amines like morpholine

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• high selectivities was the use of a dual catalyst system consisting of G2 as the anionic PTC and amino acids I for in situ formation of a more reactive enamine intermediate which then undergoes the stereoselective α-fluorination followed by hydrolysis of the resulting imines to give targets 11 [83]. α

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• of imides with alkyl halogenides, and the results are presented in this paper. Until now, ball milling N-alkylations of ureas [15], hydrazones [16], imines [17][18], pyridines [19], pyrimidines [20], imidazoles [21], secondary amines [22], as well as allylic alkylation reactions [23] were reported in

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

• -workers in the year 2000 [26][27][28][29]. It oxidizes diverse functionalities such as amines, imines, alcohols etc. [30]. Later, it was demonstrated that IBX can also be used as a reagent for oxidative dehydrogenation of benzylic carbons in various aromatic systems via single electron transfer (SET) and

• /or ionic pathways [31][32][33][34]. It was not until 2004, that IBX was applied in the oxidative dehydrogenation of functionalized cyclic and acyclic ketones [31][32][33][34]. IBX was further harnessed in the oxidative dehydrogenation of 2°-amines, N-hydroxides, imines and oximes [31][32][33][34

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

• 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

• [10]. The use of cyclic imines (or surrogates thereof such as isoquinoline [11]) in the CCR is quite scarce in the literature [12][13][14]. As an example, 1-pyrroline (in the form of its trimer 3) has been reported by Smith and co-workers [15][16][17] to condense efficiently with HPA analogs 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

• reaction of monosubstituted o-phenylenediamines 11a,f–i with pyruvic ethyl ester (18a) or its acid 18b and postulated that an equilibrium between Z E imines 19, 20 and enamine 21 is quickly reached and the rate-determining reaction step is a subsequent intramolecular cyclization yielding the regioisomeric

• group in imines 2 shifts their tautomeric equilibrium to enamines 3. Selective synthesis of both 3,4-dihydroquinoxalin-2(1H)-one regioisomers 16e (SYN) and 17e (ANTI). The proposed mechanism for the synthesis of 3-methylquinoxalin-2(1H)-one regioisomers 22 and 23. In the case of starting 11g (Y: -H

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

• ). During this study we observed common byproducts related to the reductive amination of sugars [19] (Scheme 1). All the reaction conditions tested (Table 1) showed the presence of alditol 4 as a result of sodium cyanoborohydride lack of selectivity [20] to reduce imines in the presence of aldehydes. When

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• basic. DMF increases solubility of imines 5, while the application of strong acid (HClO4) promotes Shiff bases protonation. Phenylpyruvic acid (1') was also applied as carbonyl component in GBB-3CR to obtain imidazopyrazoles having a carboxylic group. However, the process of decarboxylation took place

• imines 5 with impurities of the starting compounds were isolated when applying DMF with HClO4. Interestingly, in case of ethyl 2-isocyanoacetate (3b) the reaction proceeded equally well regardless of the substituent in the aldehyde. This can be connected with an increased reactivity of ethyl 2

• -isocyanoacetate (3b) compared to tert-butylisocyanide (3a) due to sterical reasons thus leveling the influence of the solubility factor of imines 5. As it has been already mentioned above, in contrast to 5-amino-N-aryl-1H-pyrazole-4-carboxamides 2, 3-amino-5-methylisoxazole (7) exhibited only properties of

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• treating asthma and post-stroke patients [16]. 1,2,4-Triazolo[1,5-a]pyridines show antifungal [17], antitumor [18], and cytotoxic [19] activities. Both types of heterocyclic cores are readily available from N-aminopyridium salts and related pyridinium-N-imines via 1,3-cycloaddition reaction [20] or

• intramolecular ring closure [21][22][23][24]. The importance of these cores for medical chemistry studies suggests that isotopically labeled pyrazolo[1,5-a]pyridines and triazolo[1,5-a]pyridines could be of interest. Recently, deuterium-labeled pyridinium-N-imines were applied to mechanistic studies of the

• conversion to pyrazolo[1,5-a]pyridines [25][26]. Such labeled N-imines were obtained starting from commercially available pyridine-d5. Since substituted deuterated pyridines are less accessible new mild and simple methods of deuterium introduction into the pyridine ring are of great interest. The N

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

• -terminated SAM with an aldehyde in solution or the condensation of an aldehyde-terminated SAM with an amine in solution [19]. These surfaces were stable in water but readily erased by acid-catalyzed hydrolysis at pH 3. The propensity of imines to be hydrolyzed under acidic conditions has also been harnessed

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

• organocatalysts with a bulky substituent at C2 were synthesized from chiral imines derived from (R)-glyceraldehyde acetonide by diastereoselective allylation followed by a sequential hydrozirconation/iodination reaction. The new compounds were found to be effective organocatalysts for the Michael addition of

• tuneable catalytic motifs to be used in organocatalysis starting from the chiral pool. Highly modular chiral aminodiol derivatives were obtained by the addition of organometallic reagents to chiral imines derived from (R)-glyceraldehyde – which is easily accessible from D-mannitol – and these were

• chiral pool, we have now focused on the synthesis of new chiral pyrrolidines capable of creating a sterically demanding environment due to the presence of a bulky 2,2-disubstituted-1,3-dioxolan-4-yl moiety at C2 from chiral imines derived from (R)-glyceraldehyde. The Michael addition of aldehydes to

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

• the family of mesoionic five-membered heterocycles, of which the sydnones (1,2,3-oxadiazolium-5-olates), sydnone imines (1,2,3-oxadiazolium-5-aminides), and 1,3,4-thiadiazolium derived mesoionics are perhaps the best known members [25][26]. While not much is known about congeners of II, diverse

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

• in 85–90% isolated yields. We also conducted similar reactions with cyclohexylamine and benzylamine instead of morpholine. In both cases, we ended up with the formation of corresponding imines (Table 1, entries 12 and 13). After the successful optimization, further extension of the reaction protocol

• . 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

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• -Haloalkyllithiums are a useful class of organometallic reagents widely employed in synthetic chemistry. In fact, they allow the direct homologation of carbonyl compounds and imines leading to β-halo-alcohols and amines that are useful building blocks [29][30][31]. This work represents a remarkable example of flash

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• -membered heterocycles [2]. In addition, some cycloaliphatic thiocarbonyl S-methanides were shown to react with strongly electron-deficient cyano-substituted ethenes via zwitterionic intermediates to yield also seven-membered cyclic ketene imines, which easily undergo further conversions [3][4][5]. In the

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

• ]. Opatz et al. developed the enantioselective syntheses of various alkaloids using the rhodium catalyst developed by Noyori [88] for the asymmetric transfer hydrogenation of imines. Interestingly, imines are formed from unstable α-aminonitrile intermediates which spontaneously eliminate HCN [89][90][91