Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• by introducing a nucleophile into the enol ether, which traps the reactive oxocarbenium ion intermediate 60, leading to the formation of THP [39]. The first example of an MAP cascade reaction was reported by Rychnovsky and co-workers using allylsilane 62 as an internal nucleophile, as shown in Scheme

• unsaturated enol ether 85 to cis-2,6-disubstituted 4-methylenetetrahydropyran 86 (55% yield) as shown in Scheme 19 was reported by Hoveyda and co-workers [53]. Funk and Cossey demonstrated that ene-carbamate could be an excellent terminating group for Prins cyclization [54]. The reaction involved 87 in the

• introducing a silyl enol ether Prins cyclization concept in which oxocarbenium ion 214, generated by reacting hydroxy-substituted silyl enol ether 212 with aldehyde 213 (different types of aliphatic and aromatic as well as α,β-unsaturated aldehydes were used), was trapped by silyl enol ether [94]. A detailed

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• can be trapped by TMSCN to furnish α-(trifluoromethyl)-α-aminonitrile 183 in 40% yield. The iminium was also successfully trapped by a silyl enol ether, affording a mixture of ketone 184 and heterocycle 185 (Scheme 44). The trifluoromethyl-substituted derivatives 186a–c have then been exploited as a

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• . Particularly, the latter approach is useful for obtaining liquid crystal materials [35][36][37][38]. In the case of using 2-chloro-3,3,3-trifluoroprop-1-ene (route (c), Scheme 1), the aryl enol ether with a trifluoromethyl group was obtained [39][40]. A further example for the formation of an aryl fluoroalkyl

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• iii) an asymmetric Mukaiyama–Kiyooka aldol reaction (Scheme 16 and Scheme 17) [8]. The total synthesis was initiated with the preparation of two alkenes precursors (rac)-118 and 121. The tiglic aldehyde 115 was converted into silyl enol ether 116 followed by treatment with acetal 117 using a

• diastereoisomers. Then, the key aldol reaction of 123 with silyl enol ether 53 under optimized Mukaiyama–Kiyooka conditions, followed by TIPS deprotection, afforded adduct (3R)-(+)-11 in 63% yield and with 94% ee. Ester hydrolysis followed by acetylation of (3R)- (+)-11 produced acid derivative (+)-76 [50] in 87

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• ) gave the C-phenyl glucoside 75 [36]. Notably, the use of oxidants other than BQ gave either the TMS enol ether or the 2,3-dihydro-6-phenyl-4H-pyran-4-one. The C-3 exocyclic methylene group was introduced by a Wittig olefination, and after the manipulation of the protecting groups, a VO(acac)2-catalyzed

• and the amidation with 12c afforded 129. The synthesis was completed by the elimination of the 1° iodide, silyl ether cleavage, and hydration of the exocyclic enol ether. Of all the syntheses of FR901464 (1), the coupling of 91 with 48 is the most efficient sequence (6 steps, 45% yield). Nicolaou

Photoredox-catalyzed silyldifluoromethylation of silyl enol ethers

• Vyacheslav I. Supranovich,
• Vitalij V. Levin and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 1550–1553, doi:10.3762/bjoc.16.126

• -electron oxidation thereby supporting a photoredox cycle [22][23][24]. The silyl enol ether 2a derived from acetophenone was selected as a model substrate and the reaction with silane 1 (1.5 equiv) was evaluated (Scheme 2). The reactions were performed in dichloromethane, and reaction mixtures were

• starting enol ether. Moreover, a further increase in reaction time was accompanied by a decrease in the product yield. Finally, GC monitoring suggested complete consumption of the silyl enol ether within 6 hours. It should also be pointed out that the addition of basic additives, which are frequently

• of the alkyl group compared to that of an aryl group, which either makes radical addition reversible or attenuates the reactivity of the starting enol ether. Similarly, an aromatic substrate bearing an ortho substituent gave lower yields, which may be associated with the ability of the ortho group to

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• products. An acetal-protected aldehyde could also be used providing enol phosphonate 3g in 52% yield. In this case, prolonged reaction times led to partial evolution of 3g into enol ether 4. This transformation may be explained by an acid-mediated elimination of ethanol likely caused by trace formation of

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• % yield [29]. At this stage, the Z-configuration of the enol ether was unambiguously assigned on the basis of NOESY experiments. Specifically, NOE correlations were seen between the olefinic proton and the methylene protons of a benzyl group. The position of the 2-O-benzyl group was assigned on the basis

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• electron-rich arenes, π-excessive heterocycles, enol derivatives, and allylmetalloids. Specifically, the reactivity of 1,3,5-trimethoxybenzene, N-methylindole, acetophenone trimethylsilyl enol ether, and allyltrimethylsilane was investigated (Table 1). The Nicholas reaction products 6 and 7 (Figure 1) were

• , 825.0000; found, 825.0002. Hexacarbonyl dicobalt 3',5'-di-O-acetyl-2'-deoxy-5-(5-oxo-5-phenylhex-1-yn-1-yl)uridine (6c). To a solution of nucleoside complex 4 (0.0212 g, 30.6 μmol) in CH2Cl2 (5 mL) at 0 °C was added acetophenone trimethylsilyl enol ether (trimethyl(1-phenylvinyloxy)silane, 0.039 g, 0.20

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• traced back to silyl enol ether 10. Ent-10 was first reported by Herzon and co-workers [9] and is derived from phenol silyl ether 11 via Birch reduction and dihydroxylation. Results and Discussion Our synthesis started with meta-cresol (12) which was protected as a TIPS ether and then subjected to Birch

Efficiency Eff_syn of complex syntheses as multicomponent reactions, its algorithm and calculations based on concrete criteria

• Heiner Eckert

Beilstein J. Org. Chem. 2019, 15, 1425–1433, doi:10.3762/bjoc.15.142

• total synthesis by Tietze uses a 4CR, specifically generated for this reaction from an aldehyde, meldrum’s acid, enol ether and methanol, as a key step in the synthesis to 4 (Scheme 6) [15]. This step-saving strategy for generating novel MCRs is a fast track towards the ubiquitous use of MCRs in complex

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

• protecting group gave the intermediate 3 in good yield. Standard substitution of the hydroxy group gave the 1-deoxy-1-iododerivative 4. Base-promoted dehydroiodination, followed by Zémplen removal of the benzoate gave the desired enol ether 6, which was selected as precursor for the preparation of the first

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• -secocholestan-5-ol 33 in such a metal-catalyzed MCR led to the steroidal chroman-ketal 34 as a mixture of epimers at the center bearing the methoxy group, instead of the expected chroman spiroketal. The authors proposed the initial formation of a 6-membered enol ether, which may subsequently undergo either a

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

• excellent diastereoselectivities (1:19 and 1:99 α:β ratio, respectively). Hydroboration of the glucose enol ether 6 afforded a mixture of both diastereomers (1:2.3 α:β ratio) in good yield (43% β and 18% α isolated yields, respectively). Identification of the diastereomers was accomplished by NOESY

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• cyclopropanol by Cottle [7], the most popular methods for the preparation of cyclopropanols rely on the transformation of enolates [8][9], silyl enol ether [10][11][12], vinyl borane [13][14][15][16][17], Fischer carbene addition [18], addition of nucleophiles to carbonyl groups [19][20][21][22][23][24][25

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• ’- and 3’-hydroxy groups of a 2’-deoxynucleoside. All studied protecting groups were readily introduced with good to excellent yields using the appropriate enol ether as a reagent and 0.5 to 1 mol % p-toluenesulfonic acid as a catalyst. The protected compounds could be purified by silica gel column

• the reaction time extended, an enol ether formation takes place during the acetalization. We followed the acetal formations by 1H NMR spectroscopy, and it was shown that the formed acetal product starts to degrade in a slower consecutive step, which leads to release of the enol ether derivative, e.g

• ., 8a (Figure 2). Recently, the same kind of enol ether formation was considered in connection to an optimization of the conditions for MIP protection on secondary and benzylic hydroxy groups of mandelonitrile derivatives in a flow reactor process [9]. All of the studied acetals are stable toward basic

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

• starting material. The efficient conversion of the acetyl group into the corresponding silyl enol ether moiety delivered OX18 that may be used for further transformations. Alternatively, OX7 and phenyl hydrazine afforded the corresponding hydrazone OX19 in excellent yield that was further treated with

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• ketone was converted to a trimethylsilyl enol ether upon treatment with KHMDS/Me3SiCl. By contrast, an electron-withdrawing p-nitrophenyl group was not tolerated because the intermediate cyclopropene 65i underwent decomposition under the reaction conditions of the Ireland–Claisen rearrangement

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

• 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

• successful synthesis of the two 6’F-bc4,3 pyrimidine phosphoramidite building blocks 10 and 16 starting from a bicyclic silyl enol ether. The key step in the synthesis was the transformation of a gem-difluorinated tricyclic nucleoside into a ring-enlarged bicyclic fluoroenone by simultaneous desilylation and

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• presence of bases (e.g., DBU) [12], Pd-catalyzed cycloalkenylation of a silyl enol ether [13], or base-promoted ynone carbocyclizations [14][15]. Another approach through an aldol cyclization, forming the C1–C7a bond instead, has also been reported [16]. Different strategies were developed by Overman

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

• synthesize new carbocyclic nucleosides. Synthesis of dihydropyranonucleosides The success of the oxidative coupling reaction for constructing a carbocyclic nucleoside skeleton led us to develop a glycosylation reaction applicable to glycal derivatives. Since an electron-rich enol ether unit of glycal could

• oxocarbenium ion 101 to serve as an intermediate, giving a nucleoside 102. First, we attempted model reactions of the oxidative coupling to enol ether using a TMSOTf/PhI(OAc)2 system. After several attempts, we found that the reaction of 3,4-dihydro-2H-pyran (DHP, 103) with PhI(OAc)2 and TMSOTf, starting at

• /acetonitrile/isobutyronitrile/pivalonitrile greatly improved both the chemical yields and stereoselectivity, as shown in Scheme 21. The results suggested that both the solvent system and iodonium salt promoter are required for selectivity. Even though glycals have a π-electron-rich enol ether unit, reports

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

• ]annulenes as a novel series of potent and specific αv integrin antagonists starting from 4,5-benzotropone (11) (Figure 4 and Scheme 13) [73]. TBS-enol ether intermediate 68 was first formed by the Mukaiyama–Michael reaction of O-silyl ketene acetal to 4,5-benzotropone (11) at low temperature in the presence

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

• challenge in organic synthesis. We herein report that umpolung of a ketone trimethylsilyl enol ether (1 equiv) to form a discrete enolonium species, followed by addition of as little as 1.2–1.4 equivalents of a second trimethylsilyl enol ether, provides an attractive solution to this problem. A wide array

• 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

• dichloromethane constituted an optimal recipe for preparing a variety of enolonium species. We have also shown that the enolonium species 4 (R1 = Ph, R2 = H) can be produced from the corresponding TMS enol ether 1 (R1 = Ph, R2 = H) and subsequently coupled with a second molecule of enol ether 1/5 (R1/3 = Ph, R2/4

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

• produces a radical cation species, which offers electrophilic reactivity for subsequent transformations. Enol ether radical cations are among the simplest members of this class and thus have been widely used in synthetic organic chemistry [13][14][15]. The Diels–Alder reaction is a classic reaction, and

• Diels–Alder reaction have employed styrenes, the scope is not limited to such electron-rich dienophiles. Bauld and Yoon demonstrated that aryl vinyl ethers, enol ether equivalents, and aryl vinyl sulfides are also promising dienophiles for the reactions (Scheme 2) [17][20][21][22][23][24][25]. We have

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