Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• to 6a (possibly tautomerized from its imine isomer) [69]. Finally, the β-trifluoromethylated enamine 6a undergoes intramolecular azirination affording the corresponding β-trifluoromethylated 2H-azirine via a known pathway [56][57]. Conclusion In summary, we have reported an efficient hypervalent

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• our group. These were applied to the asymmetric alkylation reaction of benzophenone imine of glycine ester which has become one of the benchmark reactions for examining the performance of new phase-transfer catalysts [36]. Later in 2010, Shirakawa and Shimizu reported the synthesis of novel inherently

• reactions, optically active calix[4]arene-imine derivative 92 containing an L-prolinamide functionality was also tested as a catalyst for enantioselective aldol reactions between 70 and a variety of aromatic aldehydes 72. The anti-aldol adducts were obtained in high yields and ees (Scheme 26). Based on the

• skeleton, an L-prolinamide analogue was prepared as a model catalyst from p-butoxybenzenamine. Without calix[4]arene backbone, only 9% ee was obtained. It was also proposed that the observed enantioselectivity resulted from the approach of the enamine double bond to the Re face of the imine via a stable

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• nucleophiles, thus increasing the structural diversity of the resulting products. The first asymmetric catalytic versions were reported only in the 2010s despite tremendous achievements in catalytic asymmetric imine addition reactions [20][21][22]. Ever since, a number of catalytic asymmetric nucleophilic

• ]. An extensively used two-component variant of this reaction consists in using a preformed imine. Among chiral metal complexes, a wide variety of organocatalysts [26][27][28][29][30][31][32][33][34] has been used to promote asymmetric Mannich reactions. Among them, cinchona alkaloid 1 was employed in

• -donating and electron-withdrawing groups. The lowest yield (51%) was obtained in the reaction of a fluorinated isatin imine (R1 = Me, R2 = 7-F). The utility of this methodology was demonstrated by its application in the formal synthesis of the anticancer agent AG-041R. Furthermore, several of the formed

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• with benzophenone imine and subsequent hydrogenolysis. Keywords: aminoestrones; Buchwald–Hartwig amination; 13α-estrone; functionalization; microwave assisted reactions; Introduction Aminoestrones are of particular interest thanks to their diverse biological applications [1][2][3][4]. There exist

• derivative [17][18]. The C(sp2)–N cross-coupling of the triflate was achieved with benzophenone imine or benzylamine. The removal of the protecting groups resulted in 3-aminoestrone in high yields. Schön et al. developed two convenient protocols for the preparation of 3-aminoestrone using Pd(OAc)2 and Pd2

• -13α-estrone (13). The efficient C(sp2)–N coupling method elaborated above proved to be suitable for the reaction of 2-bromo-3-benzyl ether 2 and benzophenone imine as an amine precursor (Scheme 2). The deprotection was achieved by hydrogenolysis using a Pd/C catalyst. The resulting newly-synthesized 2

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• , there are certain bonds like imine, oxime, hydrazone, orthoester, acetal, vinyl ether and polyketal [103] that are known to undergo hydrolysis at acidic pH, while being extremely stable during blood circulation. Therefore, acid-labile bonds could be hydrolyzed in the slightly acidic microenvironment and

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

• -directed arene C–H alkenylation reaction with alkenyl phosphates using a different cobalt–NHC catalyst (Scheme 1b) [28]. Meanwhile, we have also demonstrated that pivaloyl N–H imine serves as a powerful directing group for cobalt-catalyzed arene C–H functionalization reactions such as the hydroarylation of

• alkenes and alkylation/arylation using organic halides [29][30]. These previous studies have prompted us to expand the scope of cobalt catalysis for the C–H alkenylation and thus to develop an ortho C–H alkenylation reaction of pivalophenone N–H imine with alkenyl phosphates using a new cobalt–NHC

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

• respect to the use of an enantiomeric cyclic imine in this type of reaction [83]. The formation of the possible naphthoxazino-quinoxalinone diastereomers 46 was investigated and studied by theoretical calculations (Scheme 5). In this and all previous cases, the conformational behaviour of the

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• in 64% and 58% yield, respectively. Substituted styrenes and 1-ethynylbenzene were also tolerated well, giving corresponding products 3ai–3aj in 45–50% yields. The formations of 3ah–3aj likely derives from an azo-Diels–Alder reaction of styrene or ethynylbenzene with an imine intermediate, in situ

• gives imine intermediate product 5, which was detected by TLC and GC–MS. Moreover, when separated synthesized 5 was subjected to react with 2a, the corresponding product 3aa was isolated in 89% yield. These control experiments indicate that 5 is a possible reaction intermediate. Based on these control

• homogeneous reaction with N-arylglycine esters, N-iodo intermediate 4 was generated. Eliminating a molecule of HI affords imine intermediate 5. In the presence of acetic acid, the protonated 5-H+ undergoes nucleophilic addition with C–H nucleophiles 2 to give the desired products 3. Conclusion In summary, an

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

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

• as ABT-737 [28]. As shown in Scheme 11, the key step of this synthesis was a highly diastereoselective zinc-mediated aza-Reformatsky reaction of methyl bromoacetate (9d) with enantiopure N-tert-butylsulfinyl imine 29. It led to the corresponding chiral β-amino ester 30 in both high yield (85%) and

• diastereoselective aza-Reformatsky-type carbethoxyallylation of (S)-N-tert-butylsulfinyl imine 25u with bromide 35 performed in isopropanol as solvent in the presence of zinc, LiCl and K2CO3, which afforded the corresponding chiral acrylic ester 36 as single diastereomer (98% de) in 82% yield (Scheme 14). However

• halofluoroacetate. When the opposite enantiomer of the ligand (1S,2R)-59 was used under the same reaction conditions, it provided the corresponding (3R,4S) product 62a in 70% yield and 90% ee starting from the corresponding imine 60a (Scheme 23). Unfortunately, the scope of this domino Reformatsky/cyclization

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• , isolated imine intermediate 30 under similar conditions provided 4-substituted pyrazolo[3,4-b]pyridine 31 in DMF (Scheme 5). This intramolecular coupling reaction provided highly efficient synthetic procedure for the design and synthesis of pyrazolo[3,4-b]pyridine-nucleus-based pharmacological agents with

• in situ intramolecular cyclization of 5-aminopyrazole-4-caroxylate 35 with β-haloaldehydes 36 via the corresponding imine derivative was carried out in presence of Pd(PPh3)2Cl2 (1.0 mol %), Cu2O (1.0 mol %), 1,10-phenanthroline (2.0 mol %), TBAI (6 mol %), by Batra et al. [50] to generate the

Synthesis and spectroscopic properties of β-meso directly linked porphyrin–corrole hybrid compounds

• Baris Temelli and
• Hilal Kalkan

Beilstein J. Org. Chem. 2018, 14, 187–193, doi:10.3762/bjoc.14.13

• -porphyrin, β-corrole-linked hybrid structure described a Suzuki–Miyaura cross-coupling reaction between a β-borylated corrole and meso-bromoporphyrins (Scheme 1D) [37]. Recently, we have successfully synthesized meso–meso and β-meso-linked imine-bridged porphyrin–corrole conjugates and investigated

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• formation of 1,3,4-thiadiazoles (Scheme 34) [69]. Again, the sulfur anion is photooxidized by Eosin Y to produce a thiyl radical intermediate. Aerobic oxidation regenerates the photocatalyst and forms a superoxide radical anion. Subsequent thiyl radical addition to the imine moiety forms the five-membered

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

• Xinyun Liu Johnny H. Phan Benjamin J. Haugeberg Shrikant S. Londhe Michael D. Clift Department of Chemistry, The University of Kansas, 2010 Malott Hall, 1251 Wescoe Hall Drive, Lawrence, KS, 66045, United States 10.3762/bjoc.13.282 Abstract A new method for imine synthesis by way of quinone

• -catalyzed oxidative deformylation of 1,2-amino alcohols is reported. A wide range of readily accessible amino alcohols and primary amines can be reacted to provide N-protected imine products. The methodology presented provides a novel organocatalytic approach for imine synthesis and demonstrates 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

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• iminyl anion 19. After protonation and hydrolysis of the imine function, the α-trifluoromethylated ketones 16 were obtained in moderate to good yields (Scheme 8) [27]. Alkenyl MIDA (N-methylimidodiacetic) boronates 20, as functionalised alkenes, were transformed into α-trifluoromethyl-α-boryl ketones 21

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• salts 27 in equilibrium with their tautomeric imine form 28 (Scheme 18). Depending on the nature of the substituent R, the enamine or the imine form predominated (Table 3) [33]. In 2004 Mazurkiewicz and Fryczkowska discovered that the same type of compounds can be obtained in good or even very good

• ylide resonance structures. Furthermore, the authors did not observe an imine tautomeric form of the synthesized compounds as described by Schweizer (1H NMR). The isotopic exchange of acidic protons using a D2O solution in CD3CN revealed that the isotopic exchange of a proton in the α-position was

• for the synthesis of 2-aminovinylphosphonium salts 30 by reaction of (formylmethyl)triphenylphosphonium chloride (29) with aromatic amines in isopropanol in yields of 47–91% (Scheme 21). The initially obtained imine form of the product underwent tautomerization to a more stable enamine form, usually

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• ). The resulting ester 33 was then reduced to the corresponding aldehyde, followed by the formation of the terminal imine and its subsequent reduction to access the N-terminal moiety of 34. The alcohol and the amine deprotections were then achieved, followed by reprotection of the amine with a

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

• catalyst, proton transfer and, finally, 1,3-shift of alkoxycarbonyl group in the intermediate imine D to produce thiophenes 3 and 5. However, this pathway seems to be less probable, since intramolecular cyclization B → C should have lower activation energy relative to intermolecular interaction of C=S

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• 14. The capability of diaminoimidazoles in their tautomeric form 4-I to react as 1,3-N,N-dinucleophiles [38] determines the possible formation of adducts 8, whose recyclization could give imidazopyrimidines 15 or imidazodiazepines 16. The amine–imine tautomeric equilibrium is characteristic of

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

• 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

• complementary formation of the diastereomers was usually observed (Table 2, entries 3–8). Aromatic imines with electron-donating groups, 2fc and 2gc, as well as the heteroaromatic imine 2ec sometimes required longer reaction times, but worked without any significant problems (Table 2, entries 9–14). As a

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

• with Ellman’s chiral sulfinamide, mediated by KHSO4 [29], Cs2CO3 [30], Ti(OEt)4 [31][32][33], or CuSO4 [34], followed by either reduction [35][36][37][38][39][40] or addition of a nucleophile to the imine [41]. In general, there are two options (Figure 3) for the synthesis of enantiomerically pure

• from aldehydes. According to approach II, a metallated terminal alkyne is added to an N-sulfinylaldimine. In approach I, the organometallic nucleophile is transferring the amino acid side chain, in approach II, the amino acid side chain comes from the aldehyde incorporated in the imine. Results and

• imine 5h) after desilylation with TBAF (Table 2). As the benzylic proton of sulfinylimine 5h is quite acidic, approach II was not pursued for the synthesis of propargylamines analogous to tyrosine, histidine, tryptophan, and aspartate. Proteinogenic amino acids do not contain substituents, which

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• reaction (Scheme 6). The increased amount of the condensation agent T3P® obviously enables further activation of the initially formed 1H-benzo[f]isoindole-1,3(2H)-dione by electrophilic attack on the sterically easier accessible carbonyl group. As a consequence the imine condensation proceeds also with

• thermodynamic control giving exclusively the formation of the E-configured product 5. Interestingly the corresponding reaction with ortho-phenylenediamine (3n) gives rise to the regioselective formation of the pentacyclic condensation product 6, where the intramolecular imine formation formally occurred at the

• sterically more biased carbonyl group (Scheme 7). In addition to NMR spectroscopic and mass spectrometric characterization the crystal structures of the imine condensation products 5 and 6 were determined (Figure 2 and Figure 3) [50]. In similarity to 4b the twist angles of the phenyl substituents (rings A

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• presented reductive alkylation consists of a reaction of amine 4 with the appropriate aldehyde, which results in the respective imine subsequently reduced with sodium cyanoborohydride to the alkylated amine. Thus, the reaction of 4 with 1.5 molar excess of acetaldehyde followed by the in situ reduction with

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• that finally led to the formation of the phosphonodiamidate 100. The reduction of the nitro function and the hydrolysis under acidic conditions of the phosphonodiamide produced the phosphonic acid 101 [211]. As a last example, lithiated diaminophosphine borane 102 was added to imine to produce the bis

• microwave heating. The final product was isolated in 63% yield [223]. The Moedritzer–Irani reaction was also applied to introduce phosphonic acid functions on polymer or dendrimers possessing reactive amine. Accordingly, phosphonic acids were introduced on polyethyleneglycol 113 [188], polyethylene imine

• polymers side chains [226]. 6.2. Reactivity of phosphorous acid (H3PO3) with imine, nitrile and carbonyl groups The phosphorous acid function reacts with imine in the absence of solvent to produce α-amino-phosphonic acid as exemplified by the synthesis of the α-amino-phosphonic acid 118 from the imine 117

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

• tautomeric equilibrium between enol-imine and keto-enamine forms. Spirocyclizations involving non-bulky ketazinones 17 and 5-alkoxycarbonyl-1H-pyrrolediones 9. Spirocyclizations involving bulky ketazinones 22 and 5-alkoxycarbonyl-1H-pyrrolediones 9. Supporting Information Supporting Information File 295: 1H