The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• configuration in 80% yield. Next, to selectively oxidize the primary alcohol into an aldehyde, we utilized TEMPO/NaClO [22] to oxidize diol 6. However, the reaction failed to deliver aldehyde 7 (Scheme 3). Therefore, we proposed that diol 6 should be protected and the primary OH group could then be selectively

• ,THF, rt, 96%; (b) AD-mix-β, t-BuOH/H2O, 0 °C, 80%; (c) TEMPO, NaClO, CH2Cl2, −5 °C. AD = asymmetric dihydroxylation, TEMPO = 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical. Reagents and conditions: (a) PhCH(OCH3)2, PPTS, CH2Cl2, rt; (b) DIBAL-H, CH2Cl2, 0 °C, 76% in two steps. PPTS = pyridinium p

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• reaction conditions showed that cesium fluoride proved the best base. PhI(OAc)2 was the preferred oxidant over other hypervalent iodine compounds or sources of F+ or CF3+; additionally, the presence of a bis(oxazoline) as a ligand was beneficial to the reaction, as well as that of TEMPO to prevent

• ). Unlike the Pd-catalyzed reaction, this copper-catalyzed variant leads to a mixture of ortho-, meta- and para-functionalized compounds, with ortho > para > meta as the preferred order of selectivity in the case of simple pivanilide. Moreover, additional experiments in the presence of TEMPO or phenyl N

• , although giving lower yields. A broad substitution pattern on the (hetero)aryl ring was compatible with the reaction, and the “imino” C–H was selectively trifluoromethylated (Table 18). When carrying out the reaction in the presence of TEMPO, the desired reaction was almost completely shut down, while a

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• , 0 °C, 93%), (2) hydroboration/oxidation (9-BBN, THF, 70 °C; then NaBO3, H2O, 50 °C, 91%) and finally, (3) oxidative cyclization (BAIB, cat. TEMPO, CH2Cl2, 25 °C, 73%) was employed. Deprotection of the silyl ether (HF, MeCN, 25 °C, 87%) and base-induced rearrangement of the steroid skeleton via the

• ), 45 °C, 1.5 h, 78%, (k) NaBH4, EtOH, 65 °C, 5 d, 62%. Synthesis of 20-demethyl-bis-exo-cyclopamine 19 and F-nor-20,25-bis-demethyl-exo-cyclopamine 23. Reaction conditions: (a) allylcerium chloride, THF, 0 °C, 30 min, 93%; (b) 9-BBN, THF, 70 °C, 6 h; then NaBO3, 50 °C, 12 h, 91%; (c) BAIB, TEMPO

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• regioisomers and/or byproducts was detected in a crude mixture analyzed by 19F NMR. Under the best conditions shown in entry 10, we re-examined the reaction, but in the presence of TEMPO. The product formation was inhibited by TEMPO and O-trifluoromethylated TEMPO was detected in 2% by 19F NMR analysis (Table

• )diphenylsulfonium salt 3a and copper. The intermediate 4 decomposes to give the CF3 radical whose generation is supported by the TEMPO inhibition experiment. Ph2S was formed and checked by the 1H NMR spectroscopy. The resulting CF3 radical reacted directly with α,β-unsaturated ketones 1 and/or through the formation

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• the adduct of superoxide to DMPO. In contrast, an ESR study on the same solution but with DMPO being replaced by TEMP (2,3,6,6-tetramethylpiperidine) did not detect TEMPO, the oxidation product of TEMP by singlet oxygen. However, TEMPO was detected in the absence of N-phenyltetrahydroisoquinoline. The

Iron-catalyzed decarboxylative alkenylation of cycloalkanes with arylvinyl carboxylic acids via a radical process

• Jincan Zhao,
• Hong Fang,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2013, 9, 1718–1723, doi:10.3762/bjoc.9.197

• with smaller cycloalkanes. Finally two control experiments were carried out to shed light on the reaction mechanism. Addition of the radical scavenger 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO) or azobisisobutyronitrile (AIBN) completely inhibited the reaction, and almost no desired product was

Stability of SG1 nitroxide towards unprotected sugar and lithium salts: a preamble to cellulose modification by nitroxide-mediated graft polymerization

• Guillaume Moreira,
• Laurence Charles,
• Mohamed Major,
• Florence Vacandio,
• Yohann Guillaneuf,
• Catherine Lefay and
• Didier Gigmes

Beilstein J. Org. Chem. 2013, 9, 1589–1600, doi:10.3762/bjoc.9.181

• salts (LiBr or LiCl) in DMF or DMA. Contrary to TEMPO, SG1 proved to be stable in the presence of unprotected sugar, even with an excess of 100 molar equivalents of glucose. On the other hand, lithium salts in DMF or DMA clearly degrade SG1 nitroxide as proven by electron-spin resonance measurements

• knowledge, only hydroxyisopropylcellulose (HPC) has been modified by NMP under homogeneous conditions with the 2,2,6,6-tetramethyl-1-piperidinyloxy radical (TEMPO) (Figure 1) as a control agent and by using Barton ester intermediates [17]. Several hydroxyisopropylcellulose-grafted polystyrene (HPC-g-PS

• , the modification of free cellulose, i.e., cellulose with unprotected hydroxy groups, by NMP graft polymerization has not been studied yet. It has to be noted that sugar and in particular glucose have been used by Georges and co-workers [18] to degrade the TEMPO nitroxide to enhance the kinetics of

Structures of the reaction products of the AZADO radical with TCNQF₄ or thiourea

• Hideto Suzuki,
• Yuta Kawahara,
• Hiroki Akutsu,
• Jun-ichi Yamada and
• Shin’ichi Nakatsuji

Beilstein J. Org. Chem. 2013, 9, 1487–1491, doi:10.3762/bjoc.9.169

• compound; nitroxide radical; TCNQF4; thiourea; Introduction TEMPO radical (2,2,6,6-tetramethylpiperidinyl-N-oxyl) (1) is a typical nitroxide radical and is persistent because of the steric hindrance of the four neighboring methyl groups of the NO moiety protecting it from attack by various reagents

• less steric hindrance than the TEMPO radical (1). Radical 2 has recently been reported to be superior to the catalytic efficiency of 2 for oxidation of various alcohols [3]. Furthermore, it has been proved to display unique thermochromism and magnetic phase transitions [4]. More recently, it has been

• clarified to play a significant role as an efficient mediator for dye-sensitized solar cells with conversion efficiency as high as 8.6% [5]. Previously, we observed that the TEMPO radical (1) forms corresponding charge transfer (CT) complexes with appropriate acceptors such as TCNQF4 (3) [6], and even more

Hypervalent iodine/TEMPO-mediated oxidation in flow systems: a fast and efficient protocol for alcohol oxidation

• Nida Ambreen,
• Ravi Kumar and
• Thomas Wirth

Beilstein J. Org. Chem. 2013, 9, 1437–1442, doi:10.3762/bjoc.9.162

• Nida Ambreen Ravi Kumar Thomas Wirth Cardiff University, School of Chemistry, Park Place, Cardiff CF10 3AT, UK 10.3762/bjoc.9.162 Abstract Hypervalent iodine(III)/TEMPO-mediated oxidation of various aliphatic, aromatic and allylic alcohols to their corresponding carbonyl compounds was

• [4][5][6]. Hypervalent iodine compounds in general have emerged as versatile oxidizing agents with compounds such as DMP (Dess–Martin periodinane) and IBX finding regular utility as highly selective oxidizing agents [7][8][9]. The use of the nitroxyl radical TEMPO (2,2,6,6-tetramethylpiperidine-1

• -oxyl) as a catalyst in the oxidation of alcohols has gained much attention in recent years [10][11][12]. The redox cycle involves beside TEMPO also the corresponding hydroxylamine and the oxoammonium cation, which oxidizes the alcohol and is converted to TEMPO–H [13]. Hypervalent iodine(III) reagents

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• versus the substrate. In fact, the laccase-TEMPO system, which operates through an ionic route by formation of oxammonium ion as NHDs-Medox, resulted in particularly efficient promotion of the oxidation of benzyl alcohols, while it gave poor performances when applied in the presence of ethers. In

• catalytic system allowed higher conversion of hydroxyl groups. A comparison study on the effect of TEMPO and PINO radicals on the oxidation efficiency toward cellulose led to the conclusion that the NHPI/AQ oxidation mediator affords the highest content of carboxylic groups and better preserves the

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• promote the full oxidation of aminal 21 to deoxyvasicinone (4) were met with disappointment, with yields of 4 for these conditions reaching a maximum of around 40% (Table 3). In most cases, peroxide 8 was observed as a major side product. The Cu/TEMPO/DABCO catalyst system employed by Han et al. [35] for

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

• Ida Nymann Petersen,
• Jesper Langgaard Kristensen,
• Christian Tortzen,
• Torben Breindahl and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 641–646, doi:10.3762/bjoc.9.72

• alcohol 11 in good yield. Oxidation of alcohol 11 was carried out similarly to that reported elsewhere [19], using Epp and Widlanski’s TEMPO oxidation procedure [28] to furnish carboxylic acids 12 and d4-12 (Scheme 3). Finally, deprotection under basic condition followed by treatment with an acidic ion

• acceptors 7 and 8. Synthesis of GHB glucuronides 2 and d4-2 by using a Koenigs–Knorr glucuronidation approach. TEMPO: 2,2,6,6-tetramethyl-1-piperidinyloxyl, BAIB: [bis(acetoxy)iodo]benzene. Supporting Information Supporting Information File 88: 1D and 2D NMR spectra for 2 and d4-2 and all details for the

NHC-catalysed highly selective aerobic oxidation of nonactivated aldehydes

• Lennart Möhlmann,
• Stefan Ludwig and
• Siegfried Blechert

Beilstein J. Org. Chem. 2013, 9, 602–607, doi:10.3762/bjoc.9.65

• mpg-C3N4 and oxygen. NHC-catalysts derived from the corresponding salts are known to react with aldehydes to provide I and lead after oxidation to acyl cation intermediate II. Subsequent reactions with nucleophiles give esters, amides or acids. Reagents such as MnO2 [5][6][7], DDQ, TEMPO and

Asymmetric Diels–Alder reaction with >C=P– functionality of the 2-phosphaindolizine-η¹-P-aluminium(O-menthoxy) dichloride complex: experimental and theoretical results

• Rajendra K. Jangid,
• Nidhi Sogani,
• Neelima Gupta,
• Raj K. Bansal,
• Moritz von Hopffgarten and
• Gernot Frenking

Beilstein J. Org. Chem. 2013, 9, 392–400, doi:10.3762/bjoc.9.40

• determined on a Tempo apparatus and are uncorrected. NMR spectra were recorded on a Jeol EX-300 MHz spectrometer: 31P NMR at a frequency of 121.50 MHz (using H3PO4 as the external reference), 1H NMR at a frequency of 300.40 MHz and 13C NMR at a frequency of 75.50 MHz (using TMS as the internal reference

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• , entry 3) [64]. Parrikh–Doering oxidation [65] and TCCA–TEMPO mediated oxidation [66] (Table 2, entries 4 and 6, respectively) were not suitable as considerable amounts of D-talosamine building block were formed. DMP emerged as the reagent of choice for the oxidation of 5a. Interestingly, the

Asymmetric one-pot sequential Friedel–Crafts-type alkylation and α-oxyamination catalyzed by a peptide and an enzyme

• Kengo Akagawa,
• Ryota Umezawa and
• Kazuaki Kudo

Beilstein J. Org. Chem. 2012, 8, 1333–1337, doi:10.3762/bjoc.8.152

• water. After the FCAA by peptide catalyst 1, the α-oxyamination was successively performed by adding 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) and laccase directly to the reaction mixture. The desired two-step reaction product 4 was obtained with syn/anti ratio of 75:25, and the ee value of the syn

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• internal alkyne 6, which was submitted to gold-catalyzed cycloisomerization [33] to afford spiroketals 7a and 7b (the silyl ether is concomitantly hydrolyzed) as a 1:1 mixture of isomers. Exposure of this mixture to zinc chloride promoted isomerization to provide 7a in >20:1 dr. TEMPO oxidation then

• completed the synthesis of 1, the reported structure of cephalosporolide H. The opposite spiroketal isomer 1a was prepared from 6 by palladium-catalyzed cycloisomerization (steric control), desilylation and TEMPO oxidation. In neither case did the characterization data match that of the natural material

• subjected to TEMPO oxidation to afford spiroketal lactones 1b and 1c. Spectroscopic data of 1b and 1c were similar to 1a and 1, respectively. Attempts to secure an authentic sample and/or copies of original NMR spectra for the natural material were unsuccessful, but two candidates emerged as good fits to

Reduction of benzylic alcohols and α-hydroxycarbonyl compounds by hydriodic acid in a biphasic reaction medium

• Michael Dobmeier,
• Josef M. Herrmann,
• Dieter Lenoir and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 330–336, doi:10.3762/bjoc.8.36

• a trapping experiment, using HI without phosphorous, diphenylcarbinol as the substrate and TEMPO as a trapping agent for radical intermediates, the TEMPO adduct of diphenylcarbinol was detected by mass analysis. This indicates a radical mechanism of the redox comproportionation. We suggest a

• stepwise reduction by single electron transfer (SET) accompanied by the oxidation of I− to I2. The iodine, generated in the second step, is recycled by reduction with red phosphorous, regenerating hydriodic acid. Admittedly, the above-mentioned TEMPO adduct could also be generated by nucleophilic

• substitution of the alkyl iodide with reduced TEMPO. At least this would be another proof for the first reaction step. According to the redox equations of the reaction between iodine and red phosphorous, each mole of red phosphorous is able to reduce at least 1.5 mol of iodine. Catalytic amounts of hydriodic

Convergent synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9

• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2011, 7, 1182–1188, doi:10.3762/bjoc.7.137

• achieved in excellent yield using a [2 + 2] block glycosylation strategy. TEMPO-mediated selective oxidation of the primary alcohol of the tetrasaccharide derivative 8 to the carboxylic group followed by deprotection of the functional groups furnished target tetrasaccharide 1 as its 4-methoxyphenyl

• conversion of O-acetyl group to O-benzyl group [22], (iv) activation of glycosyl trichloroacetimidate and thioglycoside donors by perchloric acid supported on silica (HClO4–SiO2) [23][24][25][26], and late stage TEMPO mediated selective oxidation [27][28][29] of the primary hydroxy group to the carboxylic

• subjected to a reaction sequence involving (a) deacetylation using 0.1 M sodium methoxide in methanol; (b) TEMPO mediated selective oxidation [27][28][29] of the primary hydroxy group leaving secondary hydroxy groups unaffected in a phase transfer reaction condition and (c) removal of benzyl groups for

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• single diastereomer upon chelation with zinc chloride. TEMPO oxidation gave lactone 1, which corresponds to the reported structure of cephalosporolide H. A more detailed discussion is found in our earlier report [28]. Two mechanistic alternatives (Scheme 7) are proposed for the conversion of 6 → 17 in

Thermal rearrangement of tert-butylsulfinamide

• Veera Reddy Arava,
• Laxminarasimhulu Gorentla and
• Pramod Kumar Dubey

Beilstein J. Org. Chem. 2011, 7, 9–12, doi:10.3762/bjoc.7.2

• TEMPO a radical initiator (entries 22 and 23) or by a radical inhibitor 2,6-di-tert-butylphenol (entry 24). When the reagent 1 alone was subjected to thermal rearrangement (entry 1), complete consumption of starting material was observed. Only 27% product was isolated and 73% of the material was lost by

Synthesis and crossover reaction of TEMPO containing block copolymer via ROMP

• Olubummo Adekunle,
• Susanne Tanner and
• Wolfgang H. Binder

Beilstein J. Org. Chem. 2010, 6, No. 59, doi:10.3762/bjoc.6.59

Synthesis of gem-difluoromethylenated analogues of boronolide

• Jing Lin,
• Xiao-Long Qiu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2010, 6, No. 37, doi:10.3762/bjoc.6.37

• aldehyde 9 with the fluorine-containing building block 11 and the efficient construction of α,β-unsaturated-δ-lactones 15a–b via BAIB/TEMPO-procedure. Keywords: boronolide; gem-difluoromethylenated analogues; gem-difluoropropargylation; α,β-unsaturated-δ-lactones; Introduction (+)-Boronolide (1

• –quinoline system [26], leading to the expected alcohol 13a in 96% yield. Subsequent selective removal of the primary TBS group in 13a with D-camphor-10-sulfonic acid (CSA) yielded the diol 14a in 80% yield. As expected, treatment of compound 14a with 0.2 equiv of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO

• and the efficient construction of α,β-unsaturated-δ-lactones 15a–b via the BAIB/TEMPO-procedure. Boronolide (1), boronolide analogues 2–3 and gem-difluoromethylenated analogues 4–7. Retrosynthetic analysis of target molecules 4–7. Synthesis of target molecules 4–5. Synthesis of target molecules 6–7

Green oxidations: Titanium dioxide induced tandem oxidation coupling reactions

• Vineet Jeena and
• Ross S. Robinson

Beilstein J. Org. Chem. 2009, 5, No. 24, doi:10.3762/bjoc.5.24

• . Herein, we describe the application of titanium dioxide in conjunction with 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) as an oxidant in the synthesis of quinoxalines, via the tandem oxidation process (TOP) (Scheme 1). Results and Discussion Titanium dioxide in the anatase phase is a

• positive holes to the surface and subsequent hydroxyl radical formation [24]. It is believed that a similar interaction is taking place in our system and in conjunction with TEMPO lead to the formation of keto-aldehydes or diketones, which are trapped in situ to produce the required products. In an attempt

• TEMPO for the selective oxidation of alcohols to aldehydes and ketones. In our studies we have been examining similar systems with a view to incorporating them into tandem type processes. Conclusion In summary, we have reported the use of titanium dioxide as a tandem oxidation catalyst, demonstrated by

A biphasic oxidation of alcohols to aldehydes and ketones using a simplified packed- bed microreactor

• Andrew Bogdan and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2009, 5, No. 17, doi:10.3762/bjoc.5.17

• characterization of a simplified packed-bed microreactor using an immobilized TEMPO catalyst shown to oxidize primary and secondary alcohols via the biphasic Anelli-Montanari protocol. Oxidations occurred in high yields with great stability over time. We observed that plugs of aqueous oxidant and organic alcohol

• 100 trials without showing any loss of catalytic activity. Keywords: alcohol oxidation; flow chemistry; heterogeneous catalysis; microreactors; TEMPO; Introduction Microreactors have gained attention because they can help run chemical transformations more efficiently, more selectively, and with a

• leaching nor the need for catalyst regeneration [22]. Nitroxyl radicals, such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), immobilized on silicates [23][24][25][26][27][28][29][30][31][32], fluorous supports [33], soluble and insoluble polymers [22][34][35][36], magnetic nanoparticles [37], and ionic