Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• mixture of ketone 9e and the O-alkylated enol ether by-product, which was then reduced using NaBH4 to give alcohol 10e with 98:2 selectivity. Similarly, the reaction of 4-methoxybenzyl bromide and 2 gave ketone 9f in 35% yield without chromatography, and when reduced resulted in only a single alcohol

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• diasteroisomer was determined to be trans. Diyne 4l could be accessed in 44% yield from the exclusive 1,2-functionalization of the corresponding ene-yne. Crude NMR of the reaction did not show the presence of an allene product which could have been formed by a 1,4-functionalization. Enol ether could also be

• a simple enol ether was reactive in the transformation, we attempted to use glucal 1l but no conversion was observed. Enamide 1m could be azido-alkynylated in low yield and the product was inseparable from impurities. When dehydroalanine 1n was used in the reaction no product was formed and only

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• behaves accordingly here [66]. Specific gold–oxygen interactions are typically not invoked in mechanistic discussions, though a gold alcohol complex has been proposed in silyl enol ether protonation [67]. Equilibrium studies by Maier et al. indicate that methanol is more weakly coordinating than alkynes

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• , Shang and Fu initially demonstrated this approach by utilizing catalytic amounts of triphenylphosphine (PPh3) and sodium iodide (NaI) [67]. Upon formation of EDA complex 80, radical addition to silyl enol ether 81 was promoted under blue light irradiation, affording acetophenone product 82 (Scheme 16A

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• necessary. MF-ROMP, also termed photo-ROMP, is a novel technique to polymerize cyclic olefins. It begins with the reductive quenching of an photoexcited photocatalyst (PC) at an enol ether initiator to produce a radical cation carrier [90]. Then, the carrier undergoes cyclic addition with a cyclic olefin

• (Scheme 12B). Boydston and co-workers [91], systematically studied various pyrylium and thiopyrylium PCs (Scheme 13). It is necessary for these PCs having a high excited-state redox potential to oxidize the enol ether initiators. A range of enol ether initiators that has been successfully applied in metal

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• ). Carbamoylation of 151 gives the intermediate oxcarbazepine 152, whereafter hydrolysis of the methyl enol ether affords oxcarbazepine (153) [32][56]. 6.2.2 Ring functionalisation: Weng et al. [80] reported the synthesis of dihydrodibenzo[b,f]azepine (2a)-based pincer ligands for Rh and Ir metal complexes. The

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• exo Diels–Alder cycloaddition, which resulted in compound 159. The enol ether was oxidized by ceric ammonium nitrate (CAN) to deliver intermediate 160, which was further subjected to an iron-catalyzed hydrogen atom transfer generating tricyclic intermediate 161. Further functionalization permitted the

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• of enol-ether formation/Grignard addition lead to intermediate 43, from which simple acidic treatment led to rhodomollein XXII, while α-oxidation in the presence of rhenium oxide followed by acidic work-up afforded rhodomollein XX. Interestingly, Ding’s synthesis constitutes an efficient approach (22

• into dimethylacetal 45 by Vilsmeier reaction followed by aldehyde protection in 54% yield over two steps. A Mukaiyama aldol reaction between trimethylsilyl enol ether 46 and dimethylacetal 45 followed by Sakurai cyclization provided an inseparable mixture of C9 epimers (dr = 2:1). A catalyst

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• spirocyclization of DAS with the formation of minor enol ether product 3a and its Claisen rearrangement. (b) Synthetic strategy investigated in this work. Initial attempt at Rh(II)-catalyzed O–H insertion/Claisen rearrangement. Rh2(esp)2-catalyzed O–H insertion reactions between various DAS 1 and phenols. Two-step

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• be synthesized from silyl enol ether compound 10 via the Au(I)-catalyzed cycloisomerization reaction developed by our group [15]. The compound 10 could be constructed by the Sonogashira coupling reaction from readily prepared iodoarene 8 [12][16] and ketone 5, which could be synthesized by using

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• products existed as the pentacyclic hemiacetals 14. The 13C NMR spectrum for 14a had resonances at δ 144.5 and 104.4 ppm, consistent with an enol ether. In the 2D HMBC spectrum, crosspeaks between these double bond carbons were seen with the H2′-methylene and the H5′-acetal resonances. The characteristic

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• ]. The α-ketoester 41 was accessible from amide 38, which in turn was obtained from allylic alcohol 37. Oxidation and Horner–Wadsworth–Emmons reaction with phosphonate 39 delivered the silyl enol ether 40, which was deprotected and cyclized via a Grubbs metathesis to α-ketoester 41. Subsequent

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• , while other synthetic approaches were explored to obtain these reagents, the SN2 strategy described in this work was the most efficient. Such synthetic alternatives included: first, a sulfur(VI) fluoride exchange (SuFEx) between perfluoroalkylsulfonyl fluorides and the corresponding silyl enol ether

• scalable (i.e., a maximum of 15% by 1H NMR). Finally, due to the concentration of α-iodopropiophenone (6) employed, we detected the formation of a byproduct in the last stages of the optimization, namely the condensation of the desired product with α-propiophenone in the form of an enol ether. Once this

• byproduct was fully characterized by NMR, and the structure was confirmed by SCXRD, we conceived a hydrolysis protocol to break apart the formed enol ether (fully described in section 2.4 of Supporting Information File 1). After brief optimization, we succeeded at recovering the portion of

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• reactions (anthracene (33) and maleic anhydride (34) to the cycloaddition adduct 35 and chromene carbaldehyde 36 and enol ether 37 to the diastereomeric pyrano-chromenes 38), Alder-En reactions (oxomalonate diethyl ester (39) and β-pinene (40) to give the α-pinene derivative 41), and the thermal

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• acid (17) (Scheme 4). The β-hydroxy moiety in 44 can be installed via Sharpless dihydroxylation of the silyl enol ether derived from ketone 45. The 5,6-dihydro-α-pyrone group in ketone 45 is envisaged from protected diol 46 by the sequence of Mitsunobu esterification, ring-closing metathesis, and base

• followed by addition of TBSOTf at low temperature successfully formed the (Z)-silyl enol ether 54. Application of the Sharpless asymmetric dihydroxylation, promoted by AD-mix-β, gave the expected β-(R)-hydroxy cyclopropyl product 55 in 84% yield with moderate diastereoselectivity (dr = 2). The formation of

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• ) produces trans-2,5,5,9-tetramethylhexahydrochromene (53) while the cis-cyclized product was formed from cis-isoprenoid derivatives. Later, Hoye et al. used similar reaction conditions to cyclize dienes 54 with 1.1 equiv of Hg(TFA)2 to yield endocyclic enol ether 55 in almost quantitative yield [66]. They

• enol ether derivative 79 forming carbocyclic compounds 81 with good yields via intermediate 80 [78]. The cyclization of compounds 79 undergo regioselective addition with the triple bond in exocyclic alkene position leading to the formation of α-mercury ketone 80, which were later functionalized by

• electrophilic addition (Scheme 26). Schwartz et al. developed a new route for the synthesis of exocyclic enol ether 83 and endocyclic enol ether 85 involving a Hg(II)-induced cyclization of acetylenic alcohols 82 and 84, respectively [79]. This work revealed that the regioselectivity of the Hg(II) addition to

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• the highest result with a 56% ee. F-CD-BF4 30-1 is a nonhygroscopic, free-flowing solid with a high decomposition point (189 °C, dec). Enantioselective fluorinations of the sodium enolates of other ketones and β-keto esters with F-CD-BF4 30-1 were also investigated. The trimethylsilyl enol ether of 2

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• been demonstrated to yield superior results to batch. Higher yields and rates of reaction, and greater selectivities can often be achieved in flow. For example, the rate of the aldol reaction of a silyl enol ether 13 with 4-bromobenzaldehyde (14) showed a marked increase upon transposition to flow [87

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• ), which has been shown to display memory-enhancing properties and was also effective for the treatment of cognitive disorders. The reaction of the N-tert-butanesulfinyl imine (SS)-119 with trimethylsilyl enol ether derived from acetophenone 123 in the presence of TMSOTf at low temperature, produced β

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