Chiroptical properties of 1,3-diphenylallene-anchored tetrathiafulvalene and its polymer synthesis

• Masashi Hasegawa,
• Junta Endo,
• Seiya Iwata,
• Toshiaki Shimasaki and
• Yasuhiro Mazaki

Beilstein J. Org. Chem. 2015, 11, 972–979, doi:10.3762/bjoc.11.109

• ; found: C, 51.36; H, 4.25. Synthesis of (R)/(S)-PTDPA: A mixture of Pd(OAc)2 (8.9 mg, 40 μmol), P(t-Bu)3·HBF4 (35 mg, 120 mmol), Cs2CO3 (290 mg, 2.8 mmol) in degassed NMP (1 mL) was stirred for 20 min at 100 °C under Ar atmosphere. Then, (R)-3 (80 mg, 151 μmol) and 4,5-bis(methylthio)TTF (67 mg, 226 μmol

• various types of aryl groups. At this point, we have chosen the direct arylation of TTF in the presence of a palladium catalyst as a key reaction for the chiral polymer synthesis (Scheme 2) [22]. Thus, the chiral allenes, (R)-9 or (S)-9, react with an active palladium species, prepared in situ from Pd(OAc

• )2 and P(t-Bu)3·HBF4 salt in the presence of CsCO3, to give the chiral copolymer of (R)-PTDPA and (S)-PTDPA, respectively, after purification by column chromatography on polystyrene Bio-beads. By using gel permeation chromatography (GPC), the number-average molecular weights (Mn) of the collected

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• over a substantially longer period (Table 1, entry 4). Buchwald et al. [47] described a protocol for generation of the highly active Pd(0) catalyst from Pd(OAc)2 using water-mediated pre-activation. However, no conversion was observed here for L1 (Table 1, entry 5). Besides palladium, copper is another

Weakly nucleophilic potassium aryltrifluoroborates in palladium-catalyzed Suzuki–Miyaura reactions: relative reactivity of K[4-RC₆F₄BF₃] and the role of silver-assistance in acceleration of transmetallation

• Vadim V. Bardin,
• Anton Yu. Shabalin and
• Nicolay Yu. Adonin

Beilstein J. Org. Chem. 2015, 11, 608–616, doi:10.3762/bjoc.11.68

• [C6F5BF3] retards toward K2CO3 [39] as well as K2CO3 in a mixture with catalytic amounts of Pd(OAc)2 in refluxing MeOH [19]. Resistance of K[C6F5BF3] (1a) towards K2CO3 and Ag2O in toluene (without palladium catalyst and phosphine ligand) is confirmed by stirring the corresponding suspensions at 100 °C for

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• ), mackinazolinone (4) and vasicinone (5) have been proven to act as bronchodilatory, anti-inflammatory, antimicrobial and antidepressant agents (Figure 1) [2][3][4][5][6][7][8]. A variety of approaches have been employed to synthesize deoxyvasicione (1) and its derivatives, e.g., the Pd(OAc)2-catalyzed carbonyl

Matsuda–Heck reaction with arenediazonium tosylates in water

• Ksenia V. Kutonova,
• Marina E. Trusova,
• Andrey V. Stankevich,
• Pavel S. Postnikov and
• Victor D. Filimonov

Beilstein J. Org. Chem. 2015, 11, 358–362, doi:10.3762/bjoc.11.41

• be effective catalysts for the Matsuda–Heck arylation of styrene and ethyl acrylate in water [7]. It is noteworthy that these catalysts are not commercially available and must be synthesized from Pd(OAc)2. Roglands et al. prepared a range of tert-butyl cinnamates and stilbenes from arenediazonium

• conditions. Methyl acrylate (1a) was chosen as a model substrate as it is highly reactive in standard Matsuda–Heck reactions. Therefore, a solution of 4-nitrobenzenediazonium tosylate (2a) in water was allowed to react with 1.2 equiv of methyl acrylate (1a) in the presence of 1 mol % Pd(OAc)2 at rt, at 75 °C

• heating [13]. Thus, the aim of our next experiment was the reduction of the reaction time by using microwave irradiation (Table 1, entry 3). By means of this protocol 3aa was obtained with an almost quantitative yield with a reaction time of only 1 min. Carrying out the reaction with 1 mol % of Pd(OAc)2

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• benzylideneaniline were subjected to the acetoxylation using the Pd(OAc)2/PhI(OAc)2 system [33]. More recently, reactions involving the same and some other directing groups were studied in more detail. In most of the studies, Pd(OAc)2 was used as the catalyst, and PhI(OAc)2 or peroxides served as the oxidants. The

• (II) complex is oxidized by silver(I) ions to Cu(III) complex 18, and the C–O bond is formed via reductive elimination. The drawbacks of this method are the use of large amounts of silver triflate and alcohol and the high temperature of the reaction. The Pd(OAc)2/persulfate system was used in the

• lower temperature (50 °C instead of 100 °C, as in the case of CH-reagents 22 and 23) [53]. The ortho-acetoxylation and methoxylation of O-methyl aryl oximes 31 with Pd(OAc)2 combined with such oxidants as oxone, potassium persulfate, and (diacetoxyiodo)benzene (Scheme 7, coupling products 32 and 33

An improved procedure for the preparation of Ru(bpz)₃(PF₆)₂ via a high-yielding synthesis of 2,2’-bipyrazine

• Danielle M. Schultz,
• James W. Sawicki and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2015, 11, 61–65, doi:10.3762/bjoc.11.9

• , and we observed that the presence of excess isopropanol had little effect (Table 1, entries 6 and 7). Finally, an evaluation of the reaction temperature revealed that the coupling proceeded sluggishly at lower temperatures (Table 1, entry 8). Optimal conditions thus called for 5 mol % Pd(OAc)2, 2

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• carried out in the absence of Pd(OAc)2 (Table 1, entry 11) and without pivalic acid the yield of 4a was only 22% (Table 1, entry 12). All these results demonstrated that the additive and solvent played a crucial role in the dehydrogenative coupling reaction. The sequential reaction was performed with

• -azidophenyl)-1H-imidazole (1b) (0.85 mmol), 2-alkynoic acid (2) (1.02 mmol) and Cu(OAc)2∙H2O (0.085 mmol, 10 mol %) in toluene (8 mL) was added to sodium ascorbate (0.17 mmol, 20 mol %) at room temperature. The mixture was stirred at 80 °C for 2 h. Cu(OAc)2∙H2O (1.7 mmol), Pd(OAc)2 (0.043 mmol, 5 mol %) and

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• second step under the catalysis of Pd(OAc)2 comprised both cyclisation and oxidation in a single step: a dehydrogenative C–H amination with PhI(OAc)2 as oxidant and removal of the picolinamide group followed by oxidation with Cu(OAc)2. This strategy afforded phenanthridines in moderate to good yields (up

• reaction. Ghosh, Dhara et al. also reported a synthesis of substituted phenanthridines based on palladium-mediated Suzuki coupling (Scheme 14) [34][35]. Aerobic ligand-free domino Suzuki coupling–Michael addition reaction in the presence of Pd(OAc)2 and K3PO4 as a catalytic system in H2O was catalysed by

Palladium-catalyzed 2,5-diheteroarylation of 2,5-dibromothiophene derivatives

• Fatma Belkessam,
• Aidene Mohand,
• Jean-François Soulé,
• Abdelhamid Elias and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 2912–2919, doi:10.3762/bjoc.10.309

• et al. [38]. A fluorescent π-conjugate thiophene derivative bearing spiro[fluorene-9,4’-[4H]indeno[1,2-b]furan] substituents at C2 and C5 has been prepared in 46% yield by this reaction using Pd(OAc)2 (5 mol %) associated to PPh3 (10 mol %) as catalytic system [39]. A pyrrole derivative was coupled

• with 2,5-dibromothiophene in the presence of Pd(OAc)2 (5 mol %) and PCy3 (10 mol %) catalyst to afford the 2,5-di(pyrrolyl)thiophene in 59% yield [40]. Finally, an indolizine was also successfully coupled with 2,5-dibromothiophene in 47% yield in the presence of Pd(OAc)2 as catalyst [41]. To our

• PdCl(C3H5)(dppb) or Pd(OAc)2 catalysts. Using only 0.5 mol % Pd(OAc)2, the reaction of 1 equiv of 2,5-dibromothiophene with 2 equiv 2-ethyl-4-methylthiazole as coupling partners affords the mono- and diarylation products 1a and 1b in a 2:98 ratio and the desired product 1b was isolated in 79% yield

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• of 2,3-dihydrobenzofuran structures 43 via double-mediatory Wacker-type cyclization of alkenyl phenols 42 [61]. Pd(OAc)2 was used to catalyze the cyclization while TEMPO served as redox mediator for the electrochemical regeneration of the catalytically active Pd(II) species. In contrast to

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon–carbon bond forming reactions

• Matthieu Jouffroy,
• Rafael Gramage-Doria,
• David Sémeril,
• Dominique Armspach,
• Dominique Matt,
• Werner Oberhauser and
• Loïc Toupet

Beilstein J. Org. Chem. 2014, 10, 2388–2405, doi:10.3762/bjoc.10.249

• styrene and aryl bromides using [Pd(OAc)2] (OAc = acetate) as a palladium source [65]. In a preliminary study, 4-bromoanisole was reacted for 1 h with styrene in N,N-dimethylformamide (DMF) in the presence of Cs2CO3 (Table 3). The runs were carried out at different temperatures and L:M ratios. The highest

• + Na]+. General procedure for palladium-catalysed Heck cross-coupling reactions: In an oven-dried Schlenk tube, a solution of [Pd(OAc)2] in DMF, a solution of HUGPHOS-1/2 or WIDEPHOS ligands in DMF, aryl bromide (1 equiv), styrene (2 equiv), Cs2CO3 (2 equiv), decane (internal reference) and additional

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• requires phosphine ligands and high reaction temperatures. Thus, we considered the C2-arylation conditions reported by Yang et al. to be the better choice since mild conditions can be applied and only oxygen is required as oxidant (Table 6) [59]. Additionally, Pd(OAc)2 is a readily available and relatively

• 4d during N-arylation (monitored by GC–MS). Formation of byproduct 13 via benzylic oxidation. Routes towards 1,2-diarylindoles starting from indole; a: PhB(OH)2 (3 equiv), Pd(OAc)2 (5 mol %), AcOH, O2, rt, 12 h; b: CuI (10 mol %), DMEDA (20 mol %), K3PO4 (4 equiv), toluene, 135 °C, 12 h. Palladium

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• -diastereomer [14][15][50][51]. Based on the published findings, we have also examined the cyclisation reactions incorporating the PdII–PdIV catalytic cycle [52][53] (Scheme 6). The experiments were carried out using Pd(OAc)2 salt as a catalyst, PhI(OAc)2 as reoxidant, AcONa and Me4N+Cl− as buffer in AcOH

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

• ligand analogues. Experimental See Supporting Information File 1. C–H functionalization of axially chiral phosphorus substrates. The yields are isolated yields and the ee values are determind by HPLC. aReaction conditions: substrate (0.3 mmol), ethyl acrylate (1.5 mmol), Pd(OAc)2 (10 mol %), Ac-Gly-OH

• (20 mol %), AgOAc (1.5 mmol), TFE (3.0 mL), 100 °C, 24 h, air atmosphere; bSubstrate (0.3 mmol), PhI(OAc)2 (0.9 mmol), Pd(OAc)2 (10 mol %), TFE (3.0 mL), 100 °C, 24 h, air atmosphere; cSubstrate (0.3 mmol), TBHP (1.2 mmol), benzyl alcohol (0.75 mmol), Pd(TFA)2 (10 mol %), DCE (3.0 mL), 60 °C, air

• atmosphere; dSubstrate (0.3 mmol), PhI(TFA)2 (0.45 mmol), Pd(OAc)2 (10 mol %), MeNO2 (3.0 mL), 60 °C, 24 h, air atmosphere. C–H functionalization of P(O)R2 directed through a seven-membered cyclopalladium transition state. Synthesis of chiral and racemic substrates. Supporting Information Supporting

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• complexes from allylic benzotriazolyloxy products described herein should be feasible. In this context, N-allylbenzotriazole derivatives undergo reaction with preformed enamines, in the presence of Pd(OAc)2 and PPh3 [37]. Super-stoichiometric ZnBr2 was necessary for these reactions, in the absence of which

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• an alkyne 3 in the presence of a suitable catalytic system were not successful. However, after conversion of 2 into the corresponding aldoxime 9 the latter could be transformed into the N-oxides 7a and 7b by reaction with alkynes 3a and 3b, respectively, employing Pd(OAc)2 as the catalyst and under

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

• -dimethylaminopyridine, pyridine, 25 °C; then KOAc, MeOH, 64 °C, 85% yield for the two steps) to give 8. Generation of an enol triflate from the carbonyl group in 8 (potassium hexamethyldisilazide, phenyl bis-triflimide, THF, −20 → −10 °C, 85% yield) set stage for a Heck-reaction with methyl acrylate (cat. Pd(OAc)2, cat

Pd/C-catalyzed aerobic oxidative esterification of alcohols and aldehydes: a highly efficient microwave-assisted green protocol

• Marina Caporaso,
• Giancarlo Cravotto,
• Spyros Georgakopoulos,
• George Heropoulos,
• Katia Martina and
• Silvia Tagliapietra

Beilstein J. Org. Chem. 2014, 10, 1454–1461, doi:10.3762/bjoc.10.149

• methanol as substrate for the model reaction and PdCl2(PPh3)2 and Pd(OAc)2 as the catalysts. The reactions were performed in a professional multimode reactor (SynthWave-Milestone/MLS) which was equipped with multiple gas inlets and designed to work over a wide range of pressures and temperatures. The

• reaction chamber was loaded with oxygen (2.5 bar) and pressurized with nitrogen (up to 20 bar) [57]. Reactions were performed in the presence of benzylalcohol, K2CO3 in methanol and numerous different reaction conditions were screened (Table 1). As depicted in Table 1, Pd(OAc)2 afforded the methyl ester

• selectivity (compare Table 1, entries 3 and 7). Because of the excellent dielectric properties of charcoal, we tested activated charcoal adsorbed Pd(OAc)2 and observed complete conversion and good selectivity (Table 1, entry 8). Based on this result and on a recently published study by Stahl et al. [40], it

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• , 1 day, rt, 83%; (c) BzCl, pyr, 17 h, 0 °C to rt, 74%; (d) 4 M HCl in 1,4-dioxane, 16 h, 0 °C to rt, 76%; (e) 9, Et3N, n-BuOH, 16 h, 130 °C; (f) KOH, n-BuOH/EtOH, 16 h, 80 °C, 33%. Synthesis of 21 and 22, 3-arylcyclohexylamine derivatives of PreQ0. Reagents and conditions: (a) PhB(OH)2, Pd(OAc)2, bpy

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• GC–MS analysis of the crude mixture. Moreover a high conversion of 86% of this aryl bromide was observed using only 0.5 mol % Pd(OAc)2 as the catalyst. Then, we studied the scope of the coupling of 2-bromo-1,3-dichlorobenzene, using other 3-substituted thiophene derivatives (Scheme 3, Table 1). Both

• products were obtained. The reactivity for arylation at carbon C2 of the previously prepared 2-(2,6-dichlorophenyl)-4-methylthiophene (8b), via a second Pd-catalysed C–H bond activation, was also investigated (Scheme 4). 4-Bromobenzonitrile and 8b in the presence of 0.5 mol % Pd(OAc)2 and KOAc as the base

• bromide (1 mmol), thiophene derivative (2 mmol), KOAc (2 mmol), Pd(OAc)2 (0.005 mmol, 1.1 mg) and DMA (3 mL) were introduced in a Schlenk tube under argon equipped with a magnetic stirring bar. The Schlenk tube was placed in an oil bath pre-heated at 150 °C, and the reaction mixture was allowed to stir

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• )arylphosphonates by using L-Selectride (Scheme 2). The C–H activation/C–O formation of 2-(phenyl)phenylphosphonic acid monoethyl ester (1a) was examined with a variety of oxidants and bases in the presence of Pd(OAc)2. A multitude of oxidants such as K2S2O8, BQ, benzoyl peroxide, PhI(TFA)2, Cu(OAc)2, CuCl2, CuBr

• ). After examination of the reaction temperature (Table 1, entries 11–13) and time (Table 1, entries 14–16), the oxidative cyclization using PhI(OAc)2 (2 equiv) and KOAc (2 equiv) in the presence of Pd(OAc)2 (10 mol %) and L9 (30 mol %) gave the best result under aerobic conditions, affording 2a in 61

• % yield (isolated yield 55%, Table 1, entry 16). Both Pd(TFA)2 and Pd(OTf)2∙H2O gave inferior results compared to Pd(OAc)2 (Table 1, entries 17 and 18). To ascertain the scope of the Pd-catalyzed C–H activation followed by the C–O formation, a wide range of 2-(aryl)phenylphosphonic acid monoethyl esters 1

Palladium-catalysed cross-coupling reaction of ultra-stabilised 2-aryl-1,3-dihydro-1H-benzo[d]1,3,2-diazaborole compounds with aryl bromides: A direct protocol for the preparation of unsymmetrical biaryls

• Siphamandla Sithebe and
• Ross S. Robinson

Beilstein J. Org. Chem. 2014, 10, 1107–1113, doi:10.3762/bjoc.10.109

• decomposition of Pd(PPh3)2Cl2 catalyst to Pd-black. Moderate to good yields were obtained when of Pd(OAc)2/PCy3 or Pd(OAc)2/PPh3 combinations were used (Table 1, entries 8–11). Pd(OAc)2/PCy3 and K3PO4·H2O (Table 1, entry 9) was recognised to be the most effective combination and was thus chosen as optimal

• bromides bearing electron-rich, electron-neutral and electron-deficient functionalities using cost-effective and commercially available combination of Pd(OAc)2/PCy3 as a catalyst and K3PO4·H2O as a base. The catalytic system appeared versatile and general, tolerating a large range of functional groups such

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• dealkoxylation of acetals [65] and for desilylation reactions of silyl ethers [66]. With in situ generated Pd/C (obtained from Pd(OAc)2 and charcoal according to Felpin’s protocol) [67] an improved selectivity was observed as the cleavage of the silyl groups could be suppressed. However, reductive dealkoxylation

• conditions a chemoselective acetalization of the aldehyde, leading to 23 which was isolated in 52% yield. A similar result was obtained with Pd(OH)2/C (Table 4, entry 2). In situ formed Pd on charcoal [67], prepared from 0.5 mol % of Pd(OAc)2 as a precursor, gave an inseparable mixture of starting material

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• are located inside the cavity. (a) i) HCl, NaNO2/H2O, then KI/H2O, 58%, ii) Ph2PH, Pd(OAc)2, Et3N, MeOH, 48%; (b) i) CH3COOH, H2SO4, CCl4, I2, IO3, 85 °C, 4 h, exclusion of light, 70%; ii) C5H5N, H2O, KMnO4, reflux, 24 h, exclusion of light, 55%; iii) KOH in water (10% w/v), KMnO4, reflux, 4 h