A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• towards chiral 1,4-dicarbonyls bearing tertiary and all-carbon quaternary stereocenters via oxidative cross coupling of 2-acylimidazoles 85 with silyl enol ethers 86 (Scheme 32). Chiral Rh complex 87 was exploited as a Lewis acid catalyst for the purpose of activating the substrate towards anodic

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• anomeric boron analogue. Different conditions and reagents were tested for the hydroboration of the enol ethers 5 and 6 (including the use of catecholborane or dibromoborane at low temperature), but complex mixtures containing elimination byproducts were obtained in any condition. We were able to obtain

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• copper(II) triflate and Hünig's base, rearranges to give the corresponding 2-(arylthio)-3-alkyl-1,3-butadiene 10 [12]. Reacting methyl 2-phenylthiocyclopropyl ketone 11 with silyl enol ethers 12 in the presence of dimethylaluminium chloride leads to the functionalized cyclopentanes 13 via a highly

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• protected with the 2-cyanoethyl group. These protecting groups and the linker have to be cleaved under strongly basic and nucleophilic conditions. As a result, many sensitive groups including acetal, hemiacetal, vinyl ethers, enol ethers, aldehydes, esters, activated esters, thioesters, aziridines, epoxides

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• procedure has been described by Singh and co-workers [85], who used formylbenzoate 29 and preformed enol ethers instead of ketones in a Mukaiyama–Mannich lactamization reaction catalysed by zinc or copper under mild conditions. A large amount of diverse isoindolinones 32 (thirty-four examples) can be built

• in this manner, although, once again, ortho-substituted anilines 2 did not render the cyclic product, as the final lactamization step is probably impeded by sterical reasons. On the other hand, silyl enol ethers of acetone, acetophenone, methyl acetate, 2-hydroxyfuran and cyclohexanone worked well

• and heteroaromatic amines 2 and trimethylsilyl enol ethers 39 are combined in a three-component Mannich/lactamization reaction in the presence of an indium catalyst to yield twenty four 3-difluoroalkylisoindolinone derivatives 40. The starting 2-formylbenzoic acid 33 has been also employed in Ugi-type

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• -terminal CRD), -7, -8C, -8N, -9C, and -9N. Results and Discussion Chemistry The synthesis starts from the known enol ethers 2, 4, and 6 prepared using published methods [25][26]. Hydroborations of enol ethers have been known to give good to excellent regio- and stereoselectivity and are thus a possible

• route to 2-deoxyhepuloses 3, 5 and 7 [27][28][29][30]. The hydroboration of enol ethers 2, 4, and 6 with borane dimethyl sulfide in THF, followed by oxidation using hydrogen peroxide and sodium hydroxide gave 2-deoxygalactoheptulose 3 and 2-deoxymannoheptulose 5 in good yields (89% and 78%) and with

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• obtained β-ketoenamides are alkenes with a remarkable assembly of functional groups: they are enamides, enol ethers and α,β-unsaturated carbonyl compounds at the same time. In addition, their methyl ketone subunit is required for some of the subsequent transformations, e.g., the synthesis of pyridin-4-ols

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• enlargement via selective cyclopropane ring opening [46][47][48][49]. Consequently, the synthesis started from the previously described bicyclic silyl enol ethers 1α/β (Scheme 1) [50][51]. The two anomers of 1 were individually transformed into the trimethylsilyl (TMS)-protected sugars 2α/β by adapting and

• that the type of silyl enol ether drastically influenced the yield of the corresponding siloxydifluorocyclopropane. Whereas the TMS enol ethers were not suitable for the reaction due to instability of the silyl group, the tert-butyldimethylsilyl (TBDMS) enol ethers were poorly reactive most likely due

• duplexes and torsion angles of c) 6’F-bc4,3-DNA/DNA, and d) 6’F-bc4,3-DNA/RNA duplexes extracted from a 100 ns molecular dynamics trajectory. Synthesis of the gem-difluorinated glycal 4 from the silyl enol ethers 1α/β. Reagents and conditions: a) BSA, DCM, rt, 17 h, 86%; b) BSA, DCM, rt, 18 h, 88%; c

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• catalyst A in dichloromethane at ambient temperature, higher dilution and after prolonged reaction time. For the synthesis of furanocoumarins 3 the allyl ethers 9 were first subjected to a Ru hydride-catalyzed double bond isomerization [55][56] to furnish enol ethers 10 as inseparable mixtures of

• compounds 10a,b,d and ca. 10:1 for 10c with an adjacent coordinating methoxy group. The other two diastereoisomers were present only in trace amounts. RCM of enol ethers [57][58] 10 under the same conditions used for the synthesis of the oxepino-annellated coumarins 11 gave furanocoumarins 3 in excellent

Visible light-mediated difluoroalkylation of electron-deficient alkenes

• Vyacheslav I. Supranovich,
• Vitalij V. Levin,
• Marina I. Struchkova,
• Jinbo Hu and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2018, 14, 1637–1641, doi:10.3762/bjoc.14.139

• equivalents of the iododifluoromethyl carbanion [33][34][35][36]. We also demonstrated that iodides 1 can alkylate silyl enol ethers [37] under photoredox conditions [38][39][40]. However, the latter protocol is inapplicable to the addition to electron-deficient alkenes since a radical resulting from the

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• the oxidative coupling reactions of 96a and 96b. Summary of the oxidative coupling reaction of bis(trimethylsilyl)uracil 29 with enol ethers using the TMSOTf/PhI(OAc)2/(PhSe)2 system. Acknowledgements Our work described in this review article was supported in part by a Grant-in-Aid for Scientific

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• of carbonyls were established by Wirth et al. Nucleophile transfer from silyl enol ethers 90 delivered α-functionalized carbonyls 91 with good enantioselectivity [68]. “Umpolung” reactivity and silyl-tethered enol ethers allowed the delicate synthesis of α-functionalized carbonyls (Scheme 19). C2

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• of enolates may be used to form the 1,4-diketone products in 38 to 74% yield. Due to the use of two TMS enol ethers as precursors, an optimization of the cross-coupling should include investigating the order of addition. Keywords: 1,4-diketones; enolates; enolonium species; hypervalent iodine

• enantioselective coupling of in situ formed aldehyde enamines with excess (2 equiv) trialkylsilyl enol ethers (Scheme 1c) [27]. This reaction was proposed to proceed through a mechanism involving the attack of an enamine radical on the trialkylsilyl enol ether. The last two examples concern the even more

• challenging cross-coupling of two dissimilar ketone enolates. In this context Hirao achieved the intermolecular cross-coupling by taking advantage of the different oxidation potentials of boron enolates and trimethylsilyl enol ethers to achieve selectivity with vanadium (V, 0.625 equiv) as the oxidant (Scheme

Stepwise radical cation Diels–Alder reaction via multiple pathways

• Ryo Shimizu,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 704–708, doi:10.3762/bjoc.14.59

• been developing oxidative SET-triggered cycloadditions of enol ethers by electrocatalysis [26][27][28][29][30][31][32] in lithium perchlorate/nitromethane electrolyte solution [33]. The reactions involve a radical cation chain process and are complete using a catalytic amount of electricity. During the

• course of our study, we discovered that radical cation Diels–Alder reactions are also possible by electrocatalysis, however, the scope was limited to styrenes [34]. Described herein is a stepwise radical cation Diels–Alder reaction of enol ethers by electrocatalysis, which proceeds via multiple unique

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

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• review. The direct introduction of CF3S and CF3S(O) motifs also occupies a prime position in this review. 1 Trifluoromethylation Csp3–CF3 bond-forming reactions Trifluoromethylation of silyl enol ethers and enol acetates: After their original reports on the trifluoromethylation of aromatics in 1990 (Csp2

• –CF3 bond-forming reactions; see later in the text, Scheme 24) [6][7], Kamigata and co-workers studied silyl enol ethers in 1997 in trifluoromethylation reactions. Kamigata’s group reported that in the presence of RuCl2(PPh3)3, in benzene at 120 °C, silyl enol ethers could furnish the corresponding α

• pathway that involved Ru(II)/Ru(III) metallic species (Scheme 1). The trifluoromethylation of silyl enol ethers can also be adressed in a continuous-flow procedure. To do so, the appropriate ketones were transformed in situ into the corresponding silyl enol ethers, which were then reacted with CF3SO2Cl in

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• allow subsequent C–C functionalization at the C-5 position employing various palladium-catalyzed cross-coupling reactions thus expanding the library of available enantiopure 3,6-dihydro-2H-1,2-oxazines. Results and Discussion Numerous procedures exist for the synthesis of β-iodo enol ethers [27

• ], although the direct β-iodination of enol ethers using a suitable electrophilic iodine reagent is relatively underdeveloped. For the iodination of 4-alkoxy-3,6-dihydro-1,2-oxazines 3, we selected molecular iodine as the most simple iodination reagent in the presence of a base [28][29][30]. A clean reaction

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

• form the corresponding salts, and these generated in situ ion pairs were treated with silyl enol ethers in the presence of chiral catalysts L2–L4 to form chiral addition products. High levels of chirality transfer were generally observed for various 6-membered nitrogen-containing heterocyclic

• -methylpiperidinium iodide. Both L5 and L6 were found to promote the Mannich reaction between N-Troc-isoquinolinium chlorides and silyl enol ethers. Catalyst L6 with non-coordinating BArF− counterion was found to have a significantly higher activity than L5 with iodide counterion, probably, due to the competitive

From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• chemical shifts are in a more upfield region and the coupling constants are smaller than in other complexes such as the neutral N-heterocyclic oxocarbene (NHOC) rhodium complex ([Rh(NHOC)Cl(COD)] of 2 (R = Mes; δCcarbene = 229.7 ppm; 1JRhCcarbene = 51.5 Hz) as well as its enol ethers (δCcarbene = 171–177

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• the reaction with highly active dipolarophiles, such as electrophilic C=O [35], e.g., aldehydes [36][37][38], ketones [38][39], and imines [40], and nucleophilic enol ethers [38][41], enamides [42], and indoles [43]. Nonetheless, the reactions with the α,β-unsaturated aldehydes and ketones face

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• enol ethers [20][21]. Electron-rich and neutral indoles were efficient substrates for the reaction; however, electron-poor indoles showed attenuated reactivity even when 1.6 equivalents of SnCl4 were employed (60–63% yield, 96:4 to 96.5:3.5 er). Indoles lacking substitution at the 2-position (R1 = H

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• tolerate many sensitive functional groups, such as free alcohols, silyl enol ethers, and ketones, which makes it an attractive metal for late stage functionalization and elaboration of complex molecules. It is thought that the origin of ruthenium’s divergent behavior stems from a difference in reaction

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• appropriate donors convert to neutral radicals usually by loss of a proton. The most efficient donors for synthetic purposes contain adjacent functional groups such that the neutral radicals are resonance stabilized. Thus, ET from allylic alkenes and enol ethers generated allyl type radicals that reacted with

• compounds, that could be isolated on a gram scale, came from the research group of Kisch [39]. Additions of allylic alkenes and enol ethers to 1,2-diazines, mediated by photolyses of methanolic suspensions of CdS, resulted in the formation of alkenyl diazanes 3 (Scheme 2) [40]. Oxidation of the alkene/enol

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• loss of the chiral centre at 8-C. Reports on clarithromycin acid degradation suggest that enol ethers of this type exist as mixtures of 8E, 10Z and 8Z, 10Z isomers [49], that might even equilibrate [50]. It is not clear which step is C-8 stereo determining but we might assume that spiroketalisation of