First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• disappointment, none of these attempts led to success. When Mitsunobu chemistry fails, a hydroxy group inversion by tosylation and displacement using amine was performed. Unfortunately, attempts to carry out the reaction at higher temperature led to complete decomposition of the tosylate substrate. In the

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• the product as shown in Supporting Information File 1, Figure S16. The tosyl-related impurities (tosic acid/tosylate) were determined by CE and the level of the impurities resulted below 0.02% w/w. The introduction of tosyl groups into the methylated polymeric network only slightly modifies the

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• MnO2, condensation with 3-anilinopropionitrile, and then reaction with acetamidine gives the thiamine analogue 15. Tosylation of the alcohol and displacement of tosylate by the diphosphate trianion worked well to give ThDP analogue 17. A further objective was to show that the furan ring could be

Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

• Jan Szabo,
• Kerstin Karger,
• Nicolas Bucher and
• Gerhard Maas

Beilstein J. Org. Chem. 2014, 10, 2255–2262, doi:10.3762/bjoc.10.234

• occurred, leading to the corresponding tosylate 5-OTs instead of the chloride. Hydrochloric acid can also be used as an activator. However, the corresponding chloride salt 5-Cl was not obtained in an analytically pure form, which is why we continued to work with the tosylate. Since we used racemic

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

• , and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO− and AtO− produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because

• -OTs). Furthermore, we have used Bt-OTs for conversion of aldoximes to nitriles and this reagent was generally comparable to BOP in those reactions. This factor additionally favored the selection of these two tosylate derivatives. As can be seen from Table 2, Bt-OTs is superior to BOP, and a wide range

• this problem encountered with 4-nitrobenzyl alcohol. However, use of slightly modified conditions resulted in the formation of the desired product 1o in good yield (see Supporting Information File 1 for details). Reaction of phenol with Bt-OTs resulted in the formation of the phenyl tosylate (Table 2

A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

• Martin Popr,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142

• mixture of monosubstituted product 6I-O-p-toluenesulfonyl-β-cyclodextrin (1), unreacted β-CD, and some highly-substituted derivatives, which needed to be separated in order to receive pure tosylate 1. This fact is omitted in the original paper [17]. We used a strategy based on the repeated crystallization

• the preparation of 24 involved a 4-step protocol. In the first step, one hydroxy group of ethylene glycol was substituted by tosylate to yield 92% of 2-hydroxyethyl-4-methylbenzenesulfonate (21). Next, compound 22 was prepared by a nucleophilic substitution with sodium azide. The product of this

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

• synthetic route to prepare 1 using cheap and commercially available diethyl 2-acetamidomalonate (4) and propargyl alcohol. The desired product 1 was obtained via alkylation of malonate 4 with propargyl tosylate followed by a one-pot four-step sequence of hydrolysis, decarboxylation, diazotization and

• 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

• source of acetylene building moiety; and 2) basic reaction conditions involving a low pKa (<24) to avoid the interruption of the ethynyl proton (pKa ~24) while introducing the acetylene moiety. Propargyl tosylate, prepared from propargyl alcohol and tosyl chloride, is a safe analogue of propargyl bromide

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• , entry 2), a tosylate leaving group (Table 1, entry 4), and a halide (Table 1, entry 5). Somewhat more exotic functional groups such as a phosphonate ester (Table 1, entry 6) or a dimethyl acetal (Table 1, entry 7) were still tolerated in the reaction, albeit in more modest yields. A variety of alkylated

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• temperature when the vinyl tosylate was substituted with an electron-withdrawing group like in 85 (Scheme 22). The group of Gaumont has also reported their preliminary results for the enantioselective palladium-catalyzed C–P cross-coupling reaction between an achiral vinyl triflate 80c and a racemic secondary

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• ether 3 and subsequently to the corresponding tosylate 4. Using 3-methylbutylmagnesium bromide and applying cuprate chemistry [14], 4 was chain elongated to 5, which was deprotected to yield anti-2,4,8-trimethylnonanol (6). After oxidation to the corresponding aldehyde, the stereogenic center at

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• (tosylate) → –N3) in the PG layer, and click conjugation of the basic polypeptides (Arg8, Lys8 or His8) terminated with propargyl glycine. The ND-PG-BPP exhibited good dispersibility in water (>1.0 mg/mL) and positive zeta potential ranging from +14.2 mV to +44.1 mV at neutral pH in Milli-Q water. It was

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• -protected alcohol 152. Addition of methyllithium at low temperature [133] resulted in stereoselective conjugate attachment of the required methyl group. Deprotection of the alcohol and transformation into a suitable leaving group yielded tosylate 153. Next, the furan was cleaved oxidatively, the resulting

Silica: An efficient catalyst for one-pot regioselective synthesis of dithioethers

• Samir Kundu,
• Babli Roy and
• Basudeb Basu

Beilstein J. Org. Chem. 2014, 10, 26–33, doi:10.3762/bjoc.10.5

• showed varying results under conditions A or B, and allyl acetate did not undergo any desired reaction, but merely produced the disulfide from oxidative dimerization of the thiol (Table 1, entries 6–8). Allyl tosylate, however, produced the desired thioethers in a regioselective manner, but with

Consecutive cross-coupling reactions of 2,2-difluoro-1-iodoethenyl tosylate with boronic acids: efficient synthesis of 1,1-diaryl-2,2-difluoroethenes

• Ju Hee Kim,
• Su Jeong Choi and
• In Howa Jeong

Beilstein J. Org. Chem. 2013, 9, 2470–2475, doi:10.3762/bjoc.9.286

• Ju Hee Kim Su Jeong Choi In Howa Jeong Department of Chemistry & Medical Chemistry, Yonsei University, 1 Yonseidae-gil, Wonju, Gangwondo 220-710, Republic of Korea 10.3762/bjoc.9.286 Abstract The cross-coupling reactions of 2,2-difluoro-1-iodoethenyl tosylate (2) with 2 equiv of boronic acids in

• -difluoro-1-iodoethenyl tosylate; organo-fluorine; Introduction The synthesis of 2,2-disubstituted-1,1-difluoroethenes have received much attention to synthetic organofluorine chemists in recent years because of their unique chemical reactivities toward nucleophiles to produce monofluorinated organic

• bearing a metal functional group, a halogen substituent or a tosylate group at the vinyl carbon will provide a concise and efficient method for the synthesis of 2,2-disubstituted-1,1-difluoroethenes. Burton et al. reported a straightforward method for the preparation of 1,1-diaryl-2,2-difluoroethenes from

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• ][4]. In the recent past, synthesis of these chiral building blocks has gained significant interest leading to the publication of many reports. The most common methods include (i) reacting a chiral 1,2-propanediol with a leaving group such as a halide or a tosylate ester in the 3-position with base [5

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• protocol reported by Wang and Resnick from commercially available 4,4,4-trifluorobutanoic acid by diastereoselective enolate alkylation followed by reduction with lithium borohydride (Scheme 1) [18]. Fluorinated alcohol 1 was transformed into the corresponding tosylate ester 2 and subsequently reacted with

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• traces of the syn-isomer were detected by TLC. Conversion of 4 into tosylate 5a and acetate 5b by standard conditions (p-TsCl/cat. DMAP in pyridine and acetic anhydride/cat. DMAP/triethylamine, respectively) proceeded in 81 and 88% yield, respectively. In contrast, treatment of alcohol 4 with diethyl

• allene synthesis by copper-mediated SN2’-substitution [51] (Table 1, see below). In order to establish suitable reaction conditions, we first examined the synthesis of the butyl-substituted model substrate 6a. Treatment of propargyl tosylate 5a with the organocopper reagent formed in situ from n-BuMgCl

• and 9). After these successful model studies, we introduced substituents into the allene which can be removed at a later stage. Treatment of propargyl tosylate 5a with lithium dibromocuprate [57][58][59] or the silylcuprate (PhMe2Si)2CuCNLi2 [60][61] afforded the allenes 6b and 6c with 68 and 77

Cyclization of substitued 2-(2-fluorophenylazo)azines to azino[1,2-c]benzo[d][1,2,4]triazinium derivatives

• Aleksandra Jankowiak,
• Emilia Obijalska and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2013, 9, 1873–1880, doi:10.3762/bjoc.9.219

• cyclization was carried out with sunlight and tosylate 1c was isolated in pure form in 90% yield. In contrast, cation 1d partially decomposed during the workup, presumably due to the activation by means of the fluorine atoms and their electron-withdrawing effect. A pure sample of 1d could not be isolated. A

A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand

• Hideki Shimizu,
• Jeffrey C. Holder and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2013, 9, 1637–1642, doi:10.3762/bjoc.9.187

• , entries 1,2) and tosylate 10 (Table 2, entry 3) followed by in situ cyclization gave the desired product in low yield and incomplete conversion. This could potentially result from ligand hydrolysis under the given reaction conditions [29]. As an alternative to insitu cyclization of an activated

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• elimination, and treatment of the β-ketoester with TBAF in THF provided the decarboxylated and deprotected alcohol 77. The primary alcohol could be converted to the tosylate 78 in good yield with tosyl chloride, triethylamine, and trimethylamine hydrochloride as the catalyst. The alcohol 77 and tosylate 78

• contain all of the carbon atoms of epoxide fragment 5 in the correct oxidation state. The remaining steps required to access the epoxide consist of acetonide deprotection, displacement of the tosylate or another appropriate leaving group to obtain the terminal epoxide, and silyl protection. Conclusion

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• the C-1 center (dr = 9:1) in 81% yield (over three steps) [76]. The stereochemistry of 15 was unambiguously confirmed by single-crystal X-ray analysis of the related tosylate derivative 16 [77]. Deoxygenation of the C-15 primary alcohol was performed by: (a) mesylation of the alcohol with MsCl; and (b

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• a high degree of sensitivity and selectivity in discriminating between patients with probable AD and age-matched healthy controls [28]. A pyridine analogue of 46a, florbetapir ([18F]AV-45, 46b) was also prepared using a tosylate precursor with Sumitomo modules for radiosynthesis [23][29]. Compound

• the brain, as it showed particularly slow washout rate (2.89% ID/g at 60 min). Three [18F]-labeled analogues of 56c, [18F]O-FEt-PIB (62), [18F]FBTA (63), and [18F]3'-F-PIB ([18F]GE067, 64) were also prepared. Compound 62 was synthesized by using the hydroxy group of 56c to displace the tosylate of

• installation of a trifluoroacetamide and O-demethylation gave the intermediate 118 used in a Mitsunobu reaction with 2-hydroxyethyl tosylate (119). Amine deprotection to 120 and installation of the [18F] label gave the target compound 98. Both 97 and 98 showed good affinity for Aβ1-42 aggregates (Ki = 4.5 nM

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• benzenesulfonate-based radiolabelling precursors were prepared by various routes. Comparing the reactivities of 3-thiocyanatopropyl nosylate and the corresponding tosylate towards [18F]fluoride the former proved to be superior accounting for labelling yields of up to 85%. Conditions for a reliable transformation

• -conceived and was therefore adopted for our purposes. Initially, the route described by Li et al. [18] was followed to synthesise the tosylate precursor 3 (Scheme 1). As the tosylation of the alcohol 2 proceeded in low yields and led to side products that were difficult to remove and impaired the reaction

• transformed under controlled conditions into the corresponding iodides [25]. The preparation of compound 7 can be also achieved by the transformation of alcohol 2 in an Appel-type reaction, circumventing the problems encountered during the Finkelstein reaction. Conversion of 7 with silver tosylate proceeded

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• N-tosyloxycarbamate 8 and azidoformate 3 under FeBr2/Bu4NBr in EtOH conditions (see Table 1, entry 1 versus Scheme 3) likely originate from the distinct chemical property of the N–iron species (i) generated from each substrate. The possible coordination of tosylate anion to the N–iron after the N–O

Easy and direct conversion of tosylates and mesylates into nitroalkanes

• Alessandro Palmieri,
• Serena Gabrielli and
• Roberto Ballini

Beilstein J. Org. Chem. 2013, 9, 533–536, doi:10.3762/bjoc.9.58

• have now elaborated a general protocol for the direct transformation of aliphatic tosylates and mesylates into the corresponding nitro compounds. In order to optimize the reaction conditions we studied, as a test reaction, the conversion of tosylate 1a into nitropentadecane 2a (Table 1). As an initial

• technique (70 eV). IR spectra were recorded with a Perkin-Elmer Paragon 500 FTIR. General procedure for the conversion of tosylates and mesylates 1 into nitroalkanes 2. Tetrabutylammonium nitrite (TBAN, 433 mg, 1.5 mmol) was added, at room temperature, to a solution of the appropriate tosylate or mesylate 1

• , to afford the crude product 2, which was purified by flash column chromatography (heptane/ethyl acetate). Classical conversion of tosylate and mesylate into the corresponding nitroalkanes via halides. Optimization studies. Synthesis of primary nitroalkanes 2a–j. Synthesis of secondary nitroalkanes 2k