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

• asymmetric formal [3 + 2] annulation reaction between N-Boc-isatin imines 3 and 1,4-dithiane-2,5-diol (53) as equal equivalent of 2-mercaptoacetaldehyde [78]. The domino reaction catalyzed by chiral tertiary amine-squaramide catalyst 54 began with the addition of 2-mercaptoacetaldehyde to isatin imine 3

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• ), which ends up on the pyridinone ring. As alternative, a Suzuki–Miyaura coupling between 3-halogenoindoles and (2-methoxypyridyl)boronic acids followed by a deprotection of the methoxy group [7][8] or transition-metal-catalyzed annulation methods [9] have also been reported. In contrast, several

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• yield (64%, Table 2, entry 1). The annulation process did not occur without the catalyst (Table 2, entry 2). Since most of the 1,3-dipolar cycloadditions are known to work best in nonpolar solvents, toluene instead of CH2Cl2 was selected as the reaction solvent. Unfortunately, toluene was not a good

Anodic oxidation of bisamides from diaminoalkanes by constant current electrolysis

• Tatiana Golub and
• James Y. Becker

Beilstein J. Org. Chem. 2018, 14, 861–868, doi:10.3762/bjoc.14.72

• ). It has been found that anodic methoxylation of amides (and carbamates) can be utilized to form new carbon–carbon bonds [6][7] (Scheme 2). Furthermore, this anodic route could also be important from a synthetic point of view, affording ring-expansion [8][9][10] and annulation of rings [1][11][12

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• procedure for the synthesis of diene dithioacetals. A similar reaction using α-carbonyl substituted ketene dithioacetals for an addition to alkynes under iron catalysis was shown by Liu et al. before and was used for the synthesis of δ-lactams and lactones by 6-endo annulation [35]. Our approach reveals

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• -vinylphenols at 110 °C [19], the FeCl3-catalyzed areneselenyl-cyclization of aryl 2-alkynoates with ArSeSeAr at rt [20], and the Rh-catalyzed annulation of arylthiocarbamates with alkynes/AgOTf/Cu(OAc)2 at 120 °C [21]. As examples of the transition-metal-free construction of the coumarin skeleton, the Brønsted

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

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• when the σH-adducts, obtained from an allyl sulfone carbanion, were treated with a silylating agent or a Lewis acid [24]. In a similar reaction σH-adducts of benzyl carbanions of arylacetonitriles upon treatment with trialkylchlorosilanes yielded 9-cyanoacridines [25]. This [3 + 3] annulation leading

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

• carbotrifluoromethylation of N-arylacrylamides 46 with CF3SO2Na to produce oxindoles 47 [45]. Addition of the CF3 radical to such an electron-deficient alkene should be unfavourable. However, the subsequent annulation step drove the cascade process toward oxindole synthesis. The reaction utilised Langlois’ conditions with

• radical was generated from TBHP and Cu(n) via a SET process, which then, it reacted with CF3SO2Na to liberate CF3•. The subsequent addition of CF3• to the β-position of the C=C bond of the acrylamide gave the intermediate 48, which underwent an intramolecular radical annulation to produce the aryl radical

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• been found to be biologically active antagonists of adenosine receptors [82], inhibitors of cyclic-AMP-diphosphoesterase [83], and benzodiazepine receptor ligands [84][85]. Reported methods to access this structural motif include annulation between an aromatic amine and acid chloride [86] or via aza

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

• was also shown that α-cyanothioacetamides easily interact with dirhodium carboxylates to give rather stable 2:1 complexes, resulting in an evident decrease in the efficiency of the catalytic process at moderate temperatures (20–30 °C). Keywords: [4 + 1]-annulation; catalysis; diazo compounds; domino

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

• to search for new reagents for the synthesis of their imidazo[1,5-b]-annelated analogues. There are two general approaches to the construction of an imidazo[1,5-b]pyridazine scaffold: the annulation of the imidazole ring to the b-bond of the pyridazine (route A, Scheme 1) and the heterocyclization of

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• ) followed by a formal [4 + 1]-annulation reaction with ylide (tandem Michael addition/intramolecular nucleophilic substitution of dimethylsulfide by oximate anion in intermediate 94). The addition of sulfonium ylides to nitrosoalkenes can end up not only with cyclic products, but also with α,β-unsaturated

• oxidative [4 + 1]-annulation of nitrosoalkenes with 1,3-dicarbonyl compounds (Scheme 37). Optimized reaction conditions require 2 equivalents of silver carbonate as oxidizer and K2CO3 as a base to generate nitrosoalkene from a halooxime precursor 1. The plausible mechanism involves the initial conjugate

• . [4 + 1]-Annulation of nitrosoalkenes NSA with sulfonium ylides 92. Reaction of diazo compounds 96 with nitrosoalkenes NSA. Tandem Michael addition/oxidative cyclization strategy to isoxazolines 100. Acknowledgements This work was supported by Russian Foundation for Basic Research (Grants 17-03

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

• facilitate a variety of quinazolinones 44 (Scheme 12) [47]. N-Alkyl benzamides 44´ were also synthesized with this protocol. The average yield ranged from 30 to 92%. Other than methyl(hetero)arenes dimethylamides were also used as C-synthon for such intermolecular annulation to afford unsubstituted

• annulation of dihydroquinazolinones 77 with diphenylacetylene to generate polycyclic heteroarenes 78 under oxygen atmosphere (Scheme 25) [87]. Diversely substituted quinazolinones were reacted with diphenylacetylene to generate the target compounds in excellent yields. A plausible mechanistic rational

• involved the coordination of L2RuCl2 (L = p-cumene) with the more basic quinazolinone nitrogen to form complex K, which underwent β-H elimination to afford quinazolinone L and (RuLCl)-H, which further reduced to Ru0. Oxygen revived active RuI from Ru0. The neat step involved cross coupling/annulation of L

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• resolution [42][43][44][45][46][47], desymmetrization [48][49][50][51][52][53][54], de novo annulation [55][56][57][58][59][60][61], and point-to-axial chirality transfer [58][59] (for reviews, see references [31][62][63]), motivated us to expand on the utility of this class of small-molecule catalysts. We

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• intramolecular conjugate addition to an α,β-unsaturated ester [12][13][14][15] or copper-catalyzed annulation of N-arylamidines [41], among others [42]. Most of the already mentioned methods have been applied to the synthesis of 3,4-dihydroquinazolines. Among them, only a few were used for the preparation of 1,4

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• then turned our attention to the examination of a series of base catalysts for the present annulation protocol. To our delight, the reaction proceeded smoothly to give the desired 3-phenacylphthalide (3a) in 32% yield with Et3N (20 mol %) as a catalyst at 65 °C (Table 1, entry 2). To improve the

• limitations of this one-pot cascade aldol/cyclization system. Typical results are shown in Scheme 2. The annulation proceeded smoothly with β-keto acids 2 bearing diverse arene substituents to provide the corresponding isobenzofuran-1(3H)-ones in moderate to excellent yields. For para-substituted β-keto acids

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• effective strategies to construct biologically active spirocyclic oxindoles [65][66][67][68], we have built successfully interesting spirooxindoles via an NHC-catalyzed [4 + 2] annulation involving an oxidative γ-carbon activation of common α,β-unsaturated aldehydes [68]. Herein, we report another effective

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

• ], occasionally accompanied by a Wagner–Meerwein rearrangement [23]. However, no such products were found with any of the diynes 4. Our first attempts to employ 4a as a ligand with Ti(IV) resulted, somewhat surprisingly, in the addition of HCl under simultaneous annulation (three-carbon expansion [24][25]) of a

• carbocyclic five-membered ring to the 2,3-position of the bicyclic camphor-derived moiety (Scheme 2a) [20]. Reactions of 4a with halogens (e.g., bromine) or acids were even more puzzling. In addition to the annulation, an unprecedented formation of a ketone accompanied by the reduction of sulphur took place

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

• , the substitution pattern of the amidine moiety had little effect on the Au-catalyzed annulation reaction, whereas neutral or electron-donating groups on the aldehyde moiety gave a higher yield in comparison with the electron-withdrawing halides. Notably, bromo-substituted substrates were also

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

• papilloma virus type 11 (HPV11) inhibitors. These 1-indanones 99 have been synthesized using a N-heterocyclic carbene-catalyzed [4 + 1] annulation utilizing phthalaldehyde (97) and 1,2-diactivated Michael acceptors 98 (Scheme 31) [55][56]. 1.1.5 From ketones and 1,2-diketones: Another interesting approach

• 76% yield. The former 271 was obtained from the trienone 270/270’ which underwent ring closure to give the 6-membered ring [105] (Scheme 76). 2.2 From alkynes DBU and CpRu(PPh3)2Cl dual catalysts enabled a one-pot annulation of aldehyde 273 and cyclopentanone (274) to give the 1-indanone derivative

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• , dioxane, 100 °C; (c) 5 mol % Cu2O, K3PO4, DMA, 70 °C. Substrate scope for Pd-catalyzed twofold annulations. Optimization studies for annulation conditions.a Supporting Information Supporting Information File 476: Experimental part and NMR spectra of synthesized compounds. Acknowledgements The work was

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• /bjoc.12.222 Abstract A dipeptide-based urea-amide tertiary amine (DP-UAA) was shown to be an effective Brønsted base catalyst for the first asymmetric annulation reaction between 5H-thiazol-4-ones and N-itaconimides. High levels of enantioselectivity (up to 99% ee) and diastereoselectivity (>19:1 dr

• ) were obtained for a series of spirocyclic 1,4-sulfur-bridged piperidinone-based succinimides. Keywords: [4 + 2] annulation; asymmetric organocatalysis; dipeptide-based Brønsted bases; 5H-thiazol-4-ones; N-itaconimides; Introduction Sulfur-containing tetrasubstituted carbon stereocenters are widely

• , herein, we report an asymmetric [4 + 2] annulation reaction of 5H-thiazol-4-ones with N-itaconimides. The method features excellent chemo-, enantio, and diastereoselectivities, thus leading to a series of chiral spirocyclic 1,4-sulfur-bridged piperidinone-based succinimides with excellent results

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• formaldehyde through [5 + 1] annulation to afford a novel polycyclic scaffold bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-substituted maleimide in stereoselective fashion. Keywords: [5 + 1] annulation; [3 + 2] cycloaddition; one-pot reactions; stereoselective synthesis

• second [3 + 2] cycloaddition of azide compounds 2 with maleimides and sequential denitrogenation to products 7 is proposed in Scheme 2. 1,5-Diamino compounds 7 generated by one-pot reactions are good substrates for [5 + 1] annulation with aldehydes to form tetrahydroquinazolines 1 [34][35]. After

• exploring the reaction conditions, it was found that the reaction of 7a with formaldehyde in 1,4-dioxane at 110 °C afforded product 1a in 93% isolated yield (Table 2, entry 3). Other reactants such as HC(OEt)3, HCO2H, and paraformaldehyde (PFA) were also employed for the [5 + 1] annulation reactions. But