Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• that Snider’s attempt to oxidize, by epoxidation, the N,O-diacetyl derivative of compound 14 was not successful. Indeed, in our own work, the use of either NBS, MCPBA, or O2 with a transition-metal catalyst also gave unpromising results in attempts to oxidize compound 17. Future work will explore

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• ratios similar to those of the starting mixture 2. We believe that this is a result of an exo-epoxidation which is preferred in norbornene systems [78][79]. Such a functionalization is very attractive to produce new reactive building blocks bearing the norbornane scaffold. This approach can pave a

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• the corresponding cyclopropane 76 [77]. Caution is advised in view of a recent report that NaBH4 lowers the onset temperature for the thermal decomposition of DMSO [78]. The asymmetric difluorocyclopropanation has not yet been developed to the extent achieved for the epoxidation. Consequently, the

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• upon refluxing in toluene and subsequent epoxidation afforded 51 [32], which was converted to (−)-crinipelline A (15) in two steps. The synthesis of waihoensene (16) commenced with the conversion of aldehyde 52a to the corresponding hydrazone 52b, which was treated with sodium hydride under reflux to

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• manipulation of the C-4 and C-6 protecting groups gave the secondary allylic alcohol 71, which underwent an epoxidation with mCPBA to give 72. A second sequence of C-4/C-6 protection, manipulation, and oxidation gave the aldehyde 73. The disadvantages of this route include the overall length (13 or 14 steps

• cleavage of the secondary triisopropylsilyl ether were prerequisites for a vanadium-catalyzed stereoselective epoxidation of the exocyclic double bond to give 90. The C-4 hydroxy group was eventually protected as a triethylsilyl ether. Through abortive attempts, Jacobsen found that the generation of the

• exocyclic epoxide prior to the formation of the C-6–C-9 conjugated diene was necessary in order to avoid the unwanted epoxidation of the C-6–C-7 olefin. Koide employed a unique strategy in which the exocyclic epoxide was generated as the initial stereocenter (Scheme 15) [12][13]. The Sharpless asymmetric

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• isoxazolidines by means of dihydroxylation [9][10] and epoxidation [11][12] reactions. Regarding the stereochemistry, almost all of the realized additions proceed with an excellent trans stereoselectivity relative to the substituent at C-3, giving isoxazolidine-4,5-diols and isoxazolidinyl epoxides with a C-3/4

• stereochemical results are consistent with our previous findings on the direct dihydroxylation and epoxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles [9][10][11][12]. To invert the relative C-3/4-trans stereochemistry, the isoxazolidin-4-ols 5a–c were first oxidized to the corresponding ketones

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• epoxidation agent of an electron-deficient olefin intermediate, which was formed by deaminative Mannich coupling between the imine and nucleophiles such as malononitrile and methyl cyanoacetate (Scheme 64) [109]. Overall, a variety of additional examples of porphyrin-photocatalyzed heteroatom oxidations are

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• subsequent Eu(fod)3-catalyzed intermolecular Diels–Alder cycloaddition and epoxidation reactions (Scheme 5) [69]. In this stereoselective synthesis, the last biomimetic step was critical to obtain the proper enantiomer of the tetracyclic core of nanolobatolide. Amphidinolide macrolides Amphidinolides

• of the dienic compound through a Suzuki–Miyaura coupling and Julia–Kocienski olefination, followed by a Yamaguchi lactonization, and an asymmetric epoxidation in the presence of (+)-diethyl tartrate, conveniently produced (−)-amphidinolide K (4, Scheme 7). In a remarkable work, Trost et al. [72

• , an intramolecular Ru-catalyzed alkene-alkyne (Ru-AA) coupling and a late-stage epoxidation were readily accomplished, while the installation of the α,α′-dihydroxy ketone through a dihydroxylation proved difficult. Noteworthy, the structural elucidation of the THP ring of des-epoxy-amphidinolide N

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• enantioselective reactions, such as the Sharpless epoxidation [19][20][21][22][23][24], asymmetric dihydroxylation [25][26], chloroallyloboronation [27], or iodolactonization [28]. Most recently a method using the asymmetric chlorination of dodecanal by LiCl in the presence of a chiral imidazolidinone catalyst has

• also been described [29]. However, many of these methods have some drawbacks – the most important one being the insufficient enantiomeric purity for biological and commercial applications [29]. (+)-Disparlure used in most commercial lures is prepared by the Sharpless epoxidation reaction, which gives

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• reduced gauche interactions [55]. Subsequent epoxidation at the double bond directed by the hydroxy group and using m-chloroperbenzoic acid allowed to install two additional stereocenters with complete control of the relative stereochemistry in 68% yield. Such two-step synthesis proved to proceed also in

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• reagents have emerged as a class of efficient and environmentally benign nonmetal “green” oxidants [66][67][68][69][70][71][72][73]. For instance, iodosobenzene (PhIO) [74] has been widely used in many synthetic transformations. It was found that PhIO is efficient in realizing epoxidation of olefins [75

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• further oxidation to carbonyls or carboxylates. Other reactions, such as epoxidation, ether bond formation, and structural rearrangement have also been reported (Figure 7). CYP114 in gibberellin (5) biosynthesis, for example, catalyzes the unique oxidation/six-membered to five-membered ring contraction of

• crystal structures, homology models, or mechanistic information to select the residues to be mutated. For example, P450BM3 (CYP102A1) was rationally evolved to catalyze the epoxidation of amorphadiene (21) by expanding the active site, minimizing competing reactions, and facilitating substrate access

• -isozizaene (33) synthase mutants that produce different sesquiterpene skeletons. Substrate promiscuity and engineering of CYPs. a) Selected examples from using a CYP library to oxidize various monoterpenes. b) Rational engineering of P450BM3 for epoxidation of amorphadiene (21). F87A/A328L and R47L/Y51F

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 asymmetric electroepoxidation of olefins 71 in a biphasic CH2Cl2/aqueous NaCl system (Scheme 28). The constant current epoxidation of 71 in an undivided cell resulted in chiral epoxides 73 in good yields and moderate enantioselectivities [66]. In 2008, Onomura and co-workers described the

• their review article [72]. In this section, we will be presenting a concise description of the use of organocatalysts as chiral inductors in electroorganic synthesis. In 2008, Page, Marken and their group reported a method for electricity-driven asymmetric organocatalytic epoxidation. The percarbonate

• obtained via oxidation by electrogenerated CO42− [73]. Moreover, they showed that electrogenerated persulfate generated in situ via a similar anodic oxidation of H2SO4 could act as an even better oxidant in presence of catalyst 103 to achieve the epoxidation of 71'c with higher ee values (Scheme 36). In

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• include epoxidation resulting in 3,4-epoxy-7,18-dolabelladien-14-one (13) or hydroboration of 3,7,18-dolabellatriene (12, Scheme 1) that has been previously biotechnologically manufactured using CotB2W288G [103]. Another successful example is the oxidative transformation of cattleyene and phomopsen [104

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• isomer 43. Treatment of 43 with methoxide ions in methanol at room temperature for 15 min gave the desired C-5 trans-butenolide 8 (40%) along with its C-5 cis-epimer 44 (60%), which is the sole product from the base-catalyzed isomerization of 43. Epoxidation of 43 gave a C-4,5-epoxide intermediate, which

• the desired stereochemistry of the C-7 benzylic hydroxy group. Compound 46 was converted to triptonide 2 by Alder periodate reaction (NaIO4, 74%), and a sequencing m-CPBA epoxidation and basic hydrogen peroxide oxidation (H2O2/OH−) procedure (two steps, 28%). Finally, sodium borohydride reduction of 2

• new methodologies of butenolide formation. The first butenolide formation started with the reaction of ketone 68 with carbon disulfide (CS2) and iodomethane (MeI) to give the ketene dithioacetal intermediate 69, which was subjected to a Corey–Chaykovsky epoxidation, followed by acid hydrolysis to give

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• acids and their cyclic forms (pyrrolidin-2-ones) takes advantage of the stereoselective epoxidation of the aziridine acrylaldehyde 161 to predominantly (98:2) form the aziridine epoxide 162 when (S)-[diphenyl(trimethylsilyloxy)methyl]pyrrolidine was used as a catalyst (Scheme 42) [94]. A key β

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• cyclisation mechanism [27]. The absolute configuration of the intermediates nerolidyl diphosphate and the bisabolyl cation To address this question experimentally, (R)- and (S)-NPP were synthesised following a known route for enantioselective preparation of nerolidol [28] by Sharpless epoxidation of farnesol

Synthesis of polydicyclopentadiene using the Cp₂TiCl₂/Et₂AlCl catalytic system and thin-layer oxidation of the polymer in air

• Zhargolma B. Bazarova,
• Ludmila S. Soroka,
• Alex A. Lyapkov,
• Мekhman S. Yusubov and
• Francis Verpoort

Beilstein J. Org. Chem. 2019, 15, 733–745, doi:10.3762/bjoc.15.69

• located on the surface of the polymer are capable of various addition reactions (bromination, epoxidation, oxidation) forming films of several tens or hundreds of nanometers thick on the surface. However, no further penetration of reactants into the deeper polydicyclopentadiene layers occurs [28]. It is

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• (Scheme 11) [60]. Sharpless epoxidation of the allylic alcohol 48 gave a 46:11:33 mixture of (S)-48, (3R,4S)-49 and (2R,3R)-50. While (S)-48 is a product of kinetic resolution, the formation of (2R,3R)-50 results from the intramolecular opening of the oxirane ring in (3R,4S)-49. After chromatographic

• a protected serinal (R)-23 [54]. Wittig olefination extended the alkyl chain by two carbon atoms and simultaneously installed the C=C bond which was subjected to the intramolecular epoxidation to give a >20:1 mixture of aminoepoxides with the isomer (2S,3R,4R)-117 dominating. Without isolation this

• (2S,3R)-2 via Sharpless epoxidation. Reagents and conditions: a) TBHP, D-(−)-DIPT, Ti(OiPr)4, MS, CH2Cl2; b) t-BuMe2SiCl, imidazole, DMAP, DMF; c) NaIO4, RuO2, AcOEt/H2O. Synthesis of (2S,3S)-2 from the imide 51. Reagents and conditions: a) NaBH4, MeOH/CH2Cl2; b) Ac2O, pyridinium perchlorate; c) furan

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• nearly transparent and flexible upon hydrogenation [84]. Another approach to the post-functionalization of NB–COE multiblock copolymers was implemented in reference [101] via double-bond epoxidation in the presence of m-chloroperbenzoic acid (Scheme 10B). It was found that this reaction proceeds more

• actively in the COE copolymer blocks than in the parent PCOE homopolymer. The epoxidation, as well hydrogenation, influenced the thermal and crystalline properties of the multiblock copolymers resulting in the increase of Tg by 40–50 °С and Tm by 20–30 °C. It is quite natural that the degree of

• of MCM between PNB and PCOE, replotted from [90]. Post-modification of multiblock copolymers by hydrogenation (A) [85] and epoxidation (B) [101] of C=C double bonds. Acknowledgements The authors are thankful to the Russian Foundation for Basic Research (project 17-03-00596). Yu. I. Denisova was

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• [52][53], and hydrogen evolution [54]. Further, Lewis et al. employed the NB scaffold for epoxidation of styrene and other olefins [55]. In all studies, the catalyst incorporated into the NB scaffold showed increased activity as compared to the protein-free catalyst under similar conditions

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• replacement of the N-Me of 4 with the methylthiomethylene substituent of 7, nor epoxidation of 4’s side chain to give 8, offered any improvement in the biological activity. The result for 8 is particularly intriguing, as this natural product was noted to have the strongest effect upon the growth of H. pylori

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

• corresponding carbonyl group (Scheme 4) was carried out by a two-step procedure involving epoxidation of the vinylsilane 5, followed by a rearrangement of the diastereomeric mixture of epoxides 7 induced by formic acid [34][35]. The resulting ketone 8 was obtained as a 3.5:1 mixture of epimers at C3. The