A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• may undergo stereoselective trap by H2O to form alcohol epimers 2; these may then undergo a stereospecific SN2 reaction to form fluoride epimers 8; c) the fluorination and/or hydroxylation of cation 10, forming fluoride epimers 8 and alcohol epimers 2, respectively, may be reversible. This has several

• effects: firstly, reversible hydroxylation means that alcohol epimers 2 may convert to fluoride epimers 8 via cation 10 (pathway (a)); secondly, reversible fluorination and/or hydroxylation means that the diastereoselectivity of formation and/or 2 may be governed by product stability and not inherent

cis–trans-Amide isomerism of the 3,4-dehydroproline residue, the ‘unpuckered’ proline

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2016, 12, 589–593, doi:10.3762/bjoc.12.57

• hydroxylation of proline [31][32][33]. Recently we found, in a comparative study of proline analogues, that Dhp is a translationally active amino acid, which, when compared to proline, exhibited lower rates of translation [34]. In order to further understand the role and potential of Dhp, this amino acid

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• activities related to the intake of ellagitannins by higher organisms. Such urolithins show different phenolic hydroxylation patterns and have been isolated from animal feces. Concerning the activity urolithin A (23), urolithin B (24), and isourolithin A (27), all isolated from fruits of Trapa natans (water

• . Cyclization between C-2, C-7 and C-8, C-13, as well as lactonization takes place, resulting in alternariol (17). Subsequently, a methylation and a hydroxylation reaction occur, catalyzed by the respective enzymes. Structures of phenylnannolones and of enterocin, both biosynthesized via polyketide synthase

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• ) in the α-hydroxylation of indenones (where n = 1 in 77) using cumyl hydroperoxide (Scheme 19) [58]. Interestingly, the 3,4-dihydronaphthalen-1(2H)-one derivative (where n = 2 in 77) did not afford any detectable product. Transamination A range of α-amino acid derivatives have been accessed by Shi and

• -amination using β-ICPD. Meng’s cupreidine catalyzed α-hydroxylation. Shi’s biomimetic transamination process for the synthesis of α-amino acids. β-Isocupreidine catalyzed [4 + 2] cycloadditions. β-Isocupreidine catalyzed [2+2] cycloaddition. A domino reaction catalyst by cupreidine catalyst CPD-30. (a

Asymmetric α-amination of β-keto esters using a guanidine–bisurea bifunctional organocatalyst

• Minami Odagi,
• Yoshiharu Yamamoto and
• Kazuo Nagasawa

Beilstein J. Org. Chem. 2016, 12, 198–203, doi:10.3762/bjoc.12.22

• asymmetric reactions [19][20]. Recently, we disclosed an α-hydroxylation of tetralone-derived β-keto esters 2 using guanidine–bisurea bifunctional organocatalyst 1a in the presence of cumene hydroperoxide (CHP) as an oxidant (Figure 1a) [21]. This reaction provides the corresponding α-hydroxylation products

• presence of diethyl azodicarboxylate (DEAD). The α-amination of various indanone-derived β-keto esters proceeded in high yield (up to 99% yield) and with high enantioselectivity (up to 94% ee). a) Asymmetric α-hydroxylation of 2 in the presence of 1a. b) Asymmetric α-amination of 4 explored in this study

Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

• Javier Ajenjo,
• Martin Greenhall,
• Camillo Zarantonello and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 192–197, doi:10.3762/bjoc.12.21

• oxidative nucleophilic substitution for hydrogen reactions (ONSH) with organolithium or magnesium species or in vicarious nucleophilic substitution reactions (VNS) with carbon, oxygen or nitrogen nucleophiles [29]. VNS is a very powerful process for selective alkylation, amination and hydroxylation of

• nucleophiles the reactions proceeded in good yields except for diethyl chloromethylphosphonate. A very short reaction time was needed in the reaction with bromoform to avoid decomposition of the tribromomethyl anion to dibromocarbene (Table 2, entry 4). Direct hydroxylation with cumene hydroperoxide required

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• transformations: electrophilic aromatic hydroxylation to the intermediate 6, oxidation to ortho-benzoquinone 7, Baeyer–Villiger (BV) oxidation, hydrolysis to muconic acid derivative 8, and finally intramolecular conjugate addition affording 3. Under certain conditions, small amounts of intermediates 6 and 8 were

• maleic acid derivative 4 in the product mixture. Control experiments in which 8 or 3 were reacted with H2O2/H2SO4 did not provide 4. This suggests that 4 may be formed by a second hydroxylation of 6 to 9. The second electrophilic aromatic hydroxylation is a favorable process because 6 is a more activated

• yield of 4 might be increased when starting from 3-(pentafluorosulfanyl)anisole (10) or 3-(pentafluorosulfanyl)phenol (11). In these substrates, the first hydroxylation is likely to occur in the para position to the methoxy or hydroxy groups facilitating the formation of the para-benzoquinone derivative

Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

• David Porter,
• Belinda M.-L. Poon and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 2549–2556, doi:10.3762/bjoc.11.275

• ) are established catalysts of C–O bond formation, oxidising hydrocarbon substrates via hydroxylation, epoxidation and dihydroxylation pathways. Herein we report the capacity of these catalysts to promote C–N bond formation, via allylic amination of alkenes. The combination of N-Boc-hydroxylamine with

• intermediate. Conclusion FeTPA (4) and FeBPMEN (5) are established catalysts for the hydroxylation, dihydroxylation and epoxidation of hydrocarbon substrates [48][58][59][60]. In this study we have shown that they can also catalyse the allylic hydroxyamination of alkenes with N-Boc-hydroxylamine. Mechanistic

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• hydroxylations. Keywords: active site mutagenesis; biotransformation; C–H activation; cytochrome P450cam monooxygenase; hydroxylation; Introduction Selective C–H activation and oxyfunctionalisation of hydrocarbons offers a route to chiral alcohols and other industrially important synthetic building blocks from

• hydroxylation by P450cam [10][11] and various other P450s, including the bacterial P450 BM3 [12][13] and human CYPs 2A6, 2C19 and 2E1 [14][15] has been previously identified to translate well to mutants activities toward structurally distinct and more demanding substrates such as diphenylmethane [10

• Escherichia coli (E. coli), variants of the fusion enzyme catalysed the efficient, highly selective hydroxylation of ionones without the need to supply expensive nicotinamide cofactors [20]. Given the previously demonstrated affinity of P450cam for hydrophobic substrates, we were interested to see if P450cam

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• intramolecular cyclization of a chiral alkenylated pyrrolidinone, followed by hydroxylation [32], or by the intramolecular ring closure of chiral pyrrolidine diesters followed by ester and oxo group reduction [33], while the syntheses of (+)-epitashiromine starts from a chiral morpholine derivative, with nitrone

Electrochemical oxidation of cholesterol

• Jacek W. Morzycki and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2015, 11, 392–402, doi:10.3762/bjoc.11.45

• considered as analogical to the Gif-system. In this approach, hydrogen peroxide was exchanged for a process of dioxygen activation with electrochemically generated [FeII(PA)3OH2]− ions. With the system, stereoselective allylic hydroxylation of cholesteryl acetate was carried out [35]. The H-shaped one

A simple and efficient method for the preparation of 5-hydroxy-3-acyltetramic acids

• Johanna Trenner and
• Evgeny V. Prusov

Beilstein J. Org. Chem. 2015, 11, 323–327, doi:10.3762/bjoc.11.37

• oxygen is reported. The deprotection of the resulting compounds was also achieved. Keywords: heterocyclic chemistry; hydroxylation; natural products; tetramic acids; Findings 5-Hydroxy-3-acyltetramic acid is an unusual structural element which is found in the molecules of such biologically active

• . Synthesis of model tetramic acids. Synthesis of hemiaminal ethers and deprotection of the tetramic acids. Initial study of oxidation of tetramic acid 7. Condition optimization for hydroxylation of tetramic acid 7. Oxidation of tetramic acids 8 and 11. Supporting Information Supporting Information File 81

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• for the stated purpose as demonstrated retro-synthetically in Figure 2. Thus, the cis-hydroxy groups in the tetrahydroxyindolizidine/quinolizidine derivative represented by the general structure I were thought to be obtainable by a substrate-controlled hydroxylation of the corresponding cycloalkene II

Effect of cyclodextrin complexation on phenylpropanoids’ solubility and antioxidant activity

• Miriana Kfoury,
• David Landy,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2014, 10, 2322–2331, doi:10.3762/bjoc.10.241

• hydroxylation. This could explain why 1 and 2, which carry no hydroxy group, reacted little with DPPH•. The activity of 3, 4, 5, 6 and 7 was kept unchanged upon complexation with CDs. This indicated that CDs did not interfere with the active groups of these PPs during inclusion complex formation which was still

P(O)R₂-directed Pd-catalyzed C–H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands

• Rong-Bin Hu,
• Hong-Li Wang,
• Hong-Yu Zhang,
• Heng Zhang,
• Yan-Na Ma and
• Shang-dong Yang

Beilstein J. Org. Chem. 2014, 10, 2071–2076, doi:10.3762/bjoc.10.215

• were produced using the non-chiral S-phos ligand. By using 2-chlorophenylboronic acid as coupling component, we demonstrated that we could obtain the phosphate compound, but it failed to yield the P(O)Ph2 group in the arylation step. In addition, in the processes of hydroxylation, arylation

• group: The reactions of alkenylation, acetoxylation, hydroxylation and acylation occurred smoothly. Even if the products were obtained in low to moderate yields, they were optically pure (Figure 1, 2c–f). For the substrate of 4-methoxy substituted binaphthyl, we could achieve the alkenylation product 2g

• alkenylation, acetoxylation and hydroxylation. The OMe group is a relatively small group, so the ee was not very high. If the substituent was OEt, the products of alkenylation and acetoxylation (Figure 1, 2m and 2n) were obtained in moderate yield and the results showed good enantioselectivities. Although the

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• inexpensive dehydroepiandrosterone (5) by the means of a copper-mediated C–H hydroxylation in the 12-position and a palladium-catalyzed coupling of methyl acrylate to an activated enol ether in the 17-position. In synthetic direction (Scheme 2), dehydroepiandrosterone (5) was protected as its

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• hydroxylation of propargylic malonate 5 without work-up of any intermediate. Keywords: alkylation; ‘click’ chemistry; ‘clickable’ polylactide; decomposition; diethyl 2-acetamidomalonate; 2-hydroxy-4-pentynoic acid; one-pot; optimization; propargyl bromide; propargyl tosylate; safe and economical; Introduction

• hydroxylation of propargylic malonate 5 without work-up of any intermediates. Results and Discussion The synthesis of the desired precursor 1 was straightforward and outlined in Scheme 4. Propargyl alcohol, a cheap source of an acetylene moiety, was tosylated with tosyl chloride following a modified procedure

• of intermediate 6 to 1 via diazotization and hydroxylation without additional work-up or isolation of 6 [35][36][37][38][39][40]. In addition, proper choice of H2SO4 instead of HCl [41][42] for one-pot conversion of 5 to 6 could avoid the formation of the possible side product 2-chloro-4-pentynoic

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• . Regioselective oxidation of parental alkenes is a challenging task for chemical catalysts and requires several steps including protection and deprotection. Many cytochrome P450 enzymes are known to catalyse selective allylic hydroxylation under mild conditions. Here, we describe CYP154E1 from Thermobifida fusca

• -box for allylic hydroxylation in synthetic chemistry. Keywords: allylic hydroxylation; cytochrome P450; natural products; protein engineering; regiochemistry; terpenoids; Introduction Direct allylic hydroxylation yielding highly valuable allylic alcohols has been recognised for a while as one of the

• hydroxylation reactions leading to synthetically relevant intermediates [5][6][7][8][9][10][11]. In addition to chemical catalysts a range of enzymes has been studied for selective allylic hydroxylation of alkenes [12][13]. Among biosynthetic routes selective allylic hydroxylation of monoterpene olefines to

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• lipophilic backbone can form strong ionophoric complexes with certain metal cations. In this work, we demonstrate for monensin biosynthesis that, as well as ether formation, a late-stage hydroxylation step is crucial for the correct formation of the sodium monensin complex. We have investigated the last two

• steps in monensin biosynthesis, namely hydroxylation catalysed by the P450 monooxygenase MonD and O-methylation catalysed by the methyl-transferase MonE. The corresponding genes were deleted in-frame in a monensin-overproducing strain of Streptomyces cinnamonensis. The mutants produced the expected

• for the key role of late-stage hydroxylation at C-26 of the monensin molecule. Like other polyether ionophores, monensin is assembled by the polyketide biosynthetic pathway on a modular polyketide synthase (PKS) multienzyme [14]. A model has been proposed [14] for monensin biosynthesis in which an

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• atom, this time onto the indole moiety (40); this further improvement in bioavailability was attributed to blockage of the metabolic degradation of 38 and 39 which commenced with hydroxylation of the indole moiety. In the next example, we return to the world of iminosugars. Isofagomine (31, Figure 11

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• . Hydroxylation and sequential methylation of 143 leads to 144. Oxidative phenol coupling then forms the cularine alkaloid skeleton. The generated cularine enneaphylline (145) and the regioisomeric iso-cularine sarcocapnidine (141) could serve as branching points for the synthesis of further cularine derivatives

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• sources [1] including the myxobacterium Stigmatella aurantiaca [21][65], and the oral bacterium Veillonella parvula [66], although the absolute configuration has not been reported. Diastereoselective hydroxylation [67] of the chelated Z-enolate derived from 28 using the Davis oxaziridine [68] afforded the

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• derivatives with the fluorine attached to position 4 of the ring. The synthesis starts from either cis- or trans-β-aminocyclohex-4-enecarboxylic acids and involves regio- and stereoselective transformation of the ring C–C double bond through iodooxazine formation and hydroxylation, followed by hydroxy

• –fluorine or oxo–fluorine exchange. Keywords: amino acids; epoxidation; fluorination; hydroxylation; stereoselective reaction; Introduction Fluorine chemistry is an expanding area of research that has generated increasing interest in pharmaceutical and medicinal chemistry in recent years because of its

• skeleton of a β-aminocyclohexanecarboxylic acid. The synthesis starts from the Boc-protected 2-aminocyclohex-4-enecarboxylic acid or 2-aminocyclohex-3-enecarboxylic acid and involves ring C–C bond transformation by regio- and stereoselective hydroxylation via iodolactonization, followed by hydroxy–fluorine

Complete σ* intramolecular aromatic hydroxylation mechanism through O₂ activation by a Schiff base macrocyclic dicopper(I) complex

• Albert Poater and
• Miquel Solà

Beilstein J. Org. Chem. 2013, 9, 585–593, doi:10.3762/bjoc.9.63

• Grahit 101, E-17003 Girona, Spain 10.3762/bjoc.9.63 Abstract In this work we analyze the whole molecular mechanism for intramolecular aromatic hydroxylation through O2 activation by a Schiff hexaazamacrocyclic dicopper(I) complex, [CuI2(bsH2m)]2+. Assisted by DFT calculations, we unravel the reaction

• pathway for the overall intramolecular aromatic hydroxylation, i.e., from the initial O2 reaction with the dicopper(I) species to first form a CuICuII-superoxo species, the subsequent reaction with the second CuI center to form a μ-η2:η2-peroxo-CuII2 intermediate, the concerted peroxide O–O bond cleavage

• and C–O bond formation, followed finally by a proton transfer to an alpha aromatic carbon that immediately yields the product [CuII2(bsH2m-O)(μ-OH)]2+. Keywords: aromatic hydroxylation; C–H bond activation; C–H functionalization; copper; DFT calculations; mechanism; Schiff base; Introduction Bearing

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• hydroxylation conditions [39][40][41]. Using AD-mix-α and -β, we obtained mixtures of 12a-A and 12a-B in 45:55 and 13:87 ratios with overall isolated yields of 32 and 77%, respectively (Table 1, entries 1 and 2). Analogously, the asymmetric dihydroxylations of 6b and 6c produced predominantly the undesired less