Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• batch-to-batch reproducible cyclodextrin (CD) derivatives often requires functionalization at specific positions of the CD skeleton. However, the regioselective preparation of this type of CD derivatives remains a challenge in synthetic chemistry. Thus, the present study aimed to prepare all positional

• . investigated the regioselective synthesis of tris(4-tert-butylphenyl)methyl ethers on the primary rim of α-CD which resulted in predominant AD species [20]. Trityl groups for regioselective bi- and trifunctionalization of α-CD were also investigated [21]. Thus, the use of either a direct single-step or

• ). On one hand, a direct bromination of α-CD was performed under Vilsmeier/Haack conditions (reaction 3, Scheme 2) with N-bromosuccinimide (NBS) and Ph3P in N,N-dimethylformamide (DMF). Previous studies have shown that this reaction is highly regioselective for the primary rim of CD [28]. After a fast

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• finding important for oligosaccharide synthesis. Here we describe this regioselective glycosylation approach in detail. Results and Discussion In the initial strategy for synthesizing the disaccharide, the fully protected acceptor (1 or 2) was intended to be a key building block. However, an unexpected

• sugar [41][42][43] and none for the synthesis of the α-D-GalpNAc-(1-3)-D-GalpNAc motif or its precursors. We therefore set out to study this regioselective glycosylation in more detail and synthesized the necessary model donors and acceptors. Here, the simplicity of the approach showed its potential, as

• (13 and 14), thereby making anomeric purity inconsequential, and finally formation of the donors, 15 and 16, as trichloroacetimidates [49]. With both, the donors and acceptors in hand, we set out to test our hypothesis of regioselective 3-O-α-glycosylation on the 3,4-diol 9, which is based on the

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• -hydroxyaryl)pyridine derivatives bearing a carboxylate or a nitrile group suitably placed at C3 position of the aza-ring has been achieved in acceptable chemical yields with a broad functional group tolerance. This sequential C–C/C–N bond making process proceeds through a regioselective allylic alkylation/aza

• generality and scope of the reaction by reacting several aryl/heteroaryl-substituted MBH carbonates derived from acrylates 2a–j and 4-methyl-N-sulfonyl ketimines 1a–e under present sequential reaction conditions. The results are incorporated in Scheme 3. The regioselective allylic alkylation/aromatization

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• assembly of triazole-fused (hetero)cycles [24][33][34][35][36][37][38][39][40][41][42], we opted to develop a new one-pot two-step three-component reaction starting from salicylaldehydes, nitroalkenes and organic azides, without isolation of the intermediate 3-nitrochromenes, in a regioselective manner and

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• conditions led to the regioselective formation of 17-exo-heterocycles in good to excellent yields. The suppression of an acid-catalyzed thermal decarboxylation of the β-ketoester and thus a significant improvement in the yield of the desired heterocyclic products could be achieved by the preliminary

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• [10][11][12][13]. In recent years, many successful attempts to regioselective [14][15][16][17], chemoselective [18][19][20][21] or atropselective [1][22][23][24][25][26] synthesis of biaryls were presented, often taking advantage of the popular and useful Suzuki–Miyaura cross-coupling reaction

• . Genazzani and co-workers described a rapid strategy for the synthesis of potent combretastatin analogues based on the two-step regioselective Suzuki cross-coupling [14]. Beaudry and co-workers used non-symmetric dibromobenzenes in the regioselective Suzuki reactions with phenyl- and selected para

• -substituted boronic acids to obtain the desired coupling products with good selectivity and yield [15]. Recently, the synthesis of some differently para- and meta-substituted derivatives of 2,6-diaryl-3-(trifluoromethyl)pyridine by regioselective Suzuki–Miyaura reactions was also described [16]. In this case

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations

• Andrew Kenny,
• Alba Pisarello,
• Arron Bird,
• Paula G. Chirila,
• Alex Hamilton and
• Christopher J. Whiteoak

Beilstein J. Org. Chem. 2018, 14, 2366–2374, doi:10.3762/bjoc.14.212

• of a range of meta-substituted acetanilides (1h–m). In most cases the products were obtained in a regioselective manner with substitution at the least hindered C–H bond. This regioselectivity has been observed previously in Cp*Co(III)-catalysis using benzamides as substrates by ourselves and others

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• addition to imines, aziridines were also amenable to the cobalt-catalyzed hydroarylation reaction (Scheme 36) [96]. Treatment of 2-phenylpyridines 3 with varies aryl-substituted aziridines gave 1,1-diarylethane derivatives 58 in a highly regioselective manner. It is noteworthy that nucleophilic addition

• selectivity in some cases. Switchable regioselective hydroarylation of styrene using low-valent cobalt catalyst and Co(III)-catalyzed hydroarylation of alkylalkenes with indoles are remarkable examples in this manner. A wide range of C−H bonds has been successfully added to alkynes, alkenes, imines etc. to

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• the methyl group at C-10 was achieved by treatment of 8 with 1.1 equiv of K2CO3 in the presence of MeI to give bis-methylated γ-lactone-fused β-ketoester 9 in 72% yield (Scheme 3). These results demonstrated that regioselective alkylation at the two sites were possible. Notably, one diastereomeric

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• regioselective and follows the same substitution pattern as the electrophilic substitution of electron-rich heterocycles. Although highly elaborated structures are not presented, the mild reaction conditions and general functional group compatibility that the reaction exhibits make it well suited for LSF

Cobalt-catalyzed nucleophilic addition of the allylic C(sp³)–H bond of simple alkenes to ketones

• Tsuyoshi Mita,
• Masashi Uchiyama,
• Kenichi Michigami and
• Yoshihiro Sato

Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176

• Tsuyoshi Mita Masashi Uchiyama Kenichi Michigami Yoshihiro Sato Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan 10.3762/bjoc.14.176 Abstract We herein describe a cobalt/Xantphos-catalyzed regioselective addition of simple alkenes to acetophenone derivatives

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• intermediates not only in pharmaceutical chemistry but also in materials science. Thus, it is of great importance to efficiently synthesize functionalized 2-aminophenols under mild reaction conditions in a regioselective manner. Among numerous methods, the [3,3]-rearrangement of O-acyl-N-arylhydroxylamines 1

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• regioselective manner [16][20]. In cycloaddition chemistry, 1,4-quinones are applied widely both as dipolarophiles and dienophiles. In the case of [3 + 2] cycloadditions, reactions can occur chemoselectively with either the C=O or the C=C unit [21][22][23]. On the other hand, reactions with diverse 1,3-dienes

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• synthesized and applied [72]. The regioselective methoxylation of diphenyl alkene with chiral hypervalent iodine 58 afforded a mixture of 60 and 61 in moderated yield and good enantioselectivity. However, the catalytic reaction afforded the opposite regioselectivity to give rearrangement product 60 in

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• . Regioselective epoxide ring opening and 1,2-difunctionalization of alkenes are the commonly employed routes in the synthesis of such compounds. Both strategies are discussed below. 3.1 Synthesis of β-hydroxy sulfides via regioselective ring opening of epoxides The considerable ring strain present in epoxides

• getting disclosed and are surveyed below. 3.1.1.1 Alumina catalysis. With respect to heterogeneous catalysts, Posner and Rogers reported that inactivated Woelm-200 chromatographic alumina catalyzes a regioselective and stereospecific (in favor of the trans-isomer) opening of a wide variety of epoxides by

• cyclohexene oxide stereoselectively provided the trans-β-hydroxy sulfide as the only product whereas styrene oxide afforded the exclusive regioselective terminal alcohol products (Scheme 19). Both complexes could be easily recovered by filtration and were reused up to five times without any significant drop

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• -D-glucuronide products could be isolated in up to 50% yield. Similarly, regioselective esterification of unprotected allyl glucuronide 11 was performed by Juteau et al. with the acids 12–16 yielding anomeric mixtures of the respective 1-O-acyl-β-D-glucuronides 18–22 in quite acceptable yields even

• native D-glucose, D-GlcNAc or D-maltose resulted in regioselective esterification of the primary OH group, leaving all other hydroxy groups including the anomeric OH unmodified [38]. On the other hand, other authors have reported that the anomeric position can be selectively modified in a Mitsunobu

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• their work, they also utilized an important chemical attribute of cetylammonium bromide (CTAB) – namely, CTAB forms surfactant-assembled lipophilic nanoreactors stable in organic solvents, which could be used for regioselective functionalization of indenes. Therefore, they investigated the

• regioselective iodination of glycals by using CTAB and hypervalent iodine reagents for the synthesis of 2-deoxy-2-iodoacetates. In the preliminary experiments, the reaction between per-O-acetylglucal (177) and PhI(OAc)2 in CTAB and KI gave trans-2-iodo α-acetate and its corresponding bromo acetate in a 94:5

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• of copper(I) iodide as a catalyst for the regioselective difunctionalization of aromatic alkynes and alkenes with an optimal atom-economy (Scheme 4a) [34][35]. The transformation proceeds efficiently, particularly in the presence of an electron-donating substituent on the aromatic ring. The same

• the conversion of allenes 20. A regioselective 1,2-addition on the internal π-bond was observed to afford the products 21, because of the presence of a heteroatom substituent that can stabilize the radical or cationic intermediate by coordination with the copper complex (Scheme 9) [42]. However, the

• provide good levels of regiocontrol in the tandem process, the use of (aryl)(dimethyluracyl)-λ3-iodanes allows for obtaining difunctionalized indoles of type 81 resulting from the regioselective introduction of the dimethyluracyl group at the N–H position. The same group has then reported a remarkable

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• this synthetic approach for the synthesis of polysubstituted 1,2-diazoles (pyrazoles, indazoles). However, until 2013 when Taran’s group introduced the regioselective Cu(I)-phenanthroline catalysis [3] this method was of limited value due to the harsh reaction conditions and sometimes also due to low

• decarboxylation [16][95][96]. A novel strategy (Scheme 8) was recently developed by Harrity et al. (see entries 73, 74, 94, 117, 136, 137, 145–150 [32][33][34][82][89][91] in Table 4) who used trimethylsilyl acetylene as a dipolarophile. After regioselective cycloaddition giving 3-trimethylsilylpyrazole (cf. also

• mechanism). Copper-catalyzed reaction of sydnones with terminal alkynes A substantial breakthrough in the field of 3-arylsydnone-terminal alkyne cycloaddition was achieved by Taran’s group in 2013 [3]. They developed a regioselective Cu(I)-phenanthroline-catalyzed variant of this reaction (i.e., copper

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• ]. They have utilized this chiral difluoroiodonium salt 13 for the asymmetric synthesis of aminofluorinated compounds 66 from 65 (Scheme 14). In addition to this, they extended this methodology for the regioselective intermolecular aminofluorination of styrenes with a racemic catalyst. The nucleophilic

• diamination of alkenes. Stereoselective oxyamination of alkenes reported by Wirth et al. Enantioselective and regioselective aminofluorination by Nevado et al. Fluorinated difunctionalization reported by Jacobsen et al. Aryl rearrangement reported by Wirth et al. α-Arylation of β-ketoesters. Asymmetric α

Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• = <1:99). Similarly, the reaction of C1 with diethylzinc or allyltributylstannane gave piperidine derivatives 2ab and 2ac with high yields and trans-selectivity (Table 1, entries 2 and 3). Also, the introduction of phenyl or cyano groups in the piperidine core proceeded in a highly regioselective

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• . Regardless of the actual halogenation species involved, regioselective halogenation of the terminal double bond of 1 would then give bridged halonium 9. From there three manifolds can be at play. Pathway a involves the addition of an oxygenated nucleophile. For X = Br, this is the case when the bromide is

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• Reactions of nucleoside sugar and nucleobase moieties An early example of the application of mechanochemistry for nucleoside derivatisation was reported by Khalafi-Nezhad and Mokhtari who effected regioselective 5′-protection of ribonucleosides and thymidine using a mortar and pestle with trityl

• (Scheme 5) [42]. In the absence of light, azobenzene derivatives were isolated as the pure E-isomers. In their original report, Sharpless and co-workers described the use of copper turnings to promote a regioselective azide–alkyne [3 + 2]-cycloaddition ("click") reaction over 24 hours [43]. High-speed

• latter reaction rapidly decomposed during work-up in solution. Regioselective and stereoselective glycosidation of adenine, N6-benzoyladenine, N4-benzoylcytosine, thymine and uracil to the corresponding β-N9-purine or β-N1-pyrimidine ribosides was achieved on gram scales under Vorbrüggen-type conditions

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• -catalyzed, stereo- and regioselective epoxide opening and subsequent nucleophilic substitution of an azide functionality. This approach enables the synthesis of the naturally D- and unnaturally L-configured GalNAc, as well as both enantiomers of the largely unknown N-acetylidosamine (IdoNAc). Keywords

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• regioselective reaction of aryl- and α-substituted phenylallenes with the hypervalent iodine (HVI) reagent 1-chloro-1,2-benziodoxol-3-one. The reaction typically results in vicinal dichlorides, except with proton-containing α-alkyl substituents, which instead give chlorinated dienes as the major product

• -chlorostyrene groups, installing them in close proximity (as shown in 3) provides two handles for rapidly achieving high-density molecular complexity. Thus, the development of strategies for their synthesis is an important endeavour. We envisioned accomplishing this by developing a chemo- and regioselective

• consistent with those achievable by other allene chlorination reactions, it was not investigated further. We next investigated the chlorination of 2a with benziodoxolone 1b [47][48][49], which proved highly regioselective. An initial reaction with 2.2 equiv of 1b in acetonitrile at room temperature failed