Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• presence of [Ir(ppy)(dtbpy)](PF6) and iPr2NEt as photoredox catalyst and a sacrificial reagent, respectively, in acetonitrile under an atmospheric pressure of CO2 (Scheme 20). 1-Phenyl-1-propyne (16n) afforded hydrocarboxylated products as a mixture of regio- and stereoisomers. 4-Octyne (16b) afforded the

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

• , Poland 10.3762/bjoc.14.214 Abstract Background: Atropisomers are very interesting stereoisomers having axial chirality resulting from restricted rotation around single bonds and are found in various classes of compounds. ortho-Substituted arylpyridines are an important group of them. A regio- and

• of 3,4,5-tribromo-2,6-dimethylpyridine with 2-methoxyphenylboronic acid under Suzuki–Miyaura reaction conditions gave the mixture of three atropisomeric stereoisomers of 3,4,5-tri-(2-methoxyphenyl)-2,6-dimethylpyridines which were separated by column chromatography and characterized by NMR

• stereoisomers of 3,4,5-tris(2-methoxyphenyl)-2,6-dimethylpyridines determined by X-ray analysis [38]. Graphical representation of kinetic, time-dependent 1H NMR analysis of (syn)-7 (100 °C). Graphical representation of kinetic, time-dependent 1H NMR analysis of (syn)-10 (120 °C). HT-NMR (300 MHz, DMSO-d6

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• enzyme is a likely candidate for the enzyme catalyzing the first step in the metabolism of both stereoisomers [23]. The subsequent step requires an additional enzyme. The pAO1 plasmid contains the gene for a D-6-hydroxynicotine oxidase (DHNO) in addition to that for LHNO. The product of the reaction

• to that of LHNO and several members of the MAO family, consistent with Nox being a nicotine oxidase similar to NicA2. Nox is reported to be able to oxidize both stereoisomers of nicotine equally well, in contrast to the stereospecificity of LHNO and DHNO. Pseudooxynicotine amine oxidase, the enzyme

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• -flat wheels, such as calixarenes or cyclodextrins, are threaded along an axle to give a pseudo[3]rotaxane architecture V–VII (Figure 2), where three sequential stereoisomers can arise. We showed that this stereoisomerism can be effectively controlled when two calix[6]arene wheels are threaded along a

• stereoisomers (V–VII) reported by our group [19][20][21]. The possible 8 discrete conformations of a calix[6]arene macrocycle [26]. Diastereoisomeric pseudorotaxanes obtained by threading a directional calixarene wheel with directional axles. Possible mechanism for the formation of the two atropoisomeric pseudo

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• ]. Calixarenes are easily functionalized at both their upper and lower rims with various stereoisomers obtainable; the initial macrocycles can be synthesized in a simple manner, they are not toxic, etc. [17][18][19][20][21][22]. Amphiphilic calixarenes are particularly interesting because they can be regarded as

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

• oxidative coupling reaction with 2,4-bis(trimethylsilyl)uracil (29) using diacetoxyiodobenzene, respectively, and the results are shown in Table 3. The reaction of 96a gave an inseparable mixture containing 4 stereoisomers of 97a–d with a ratio of 6:10:2:1.5, which was determined based on the analysis of

• cytosine analogues [63]. During the course of conversion, all the stereoisomers were separated. Among them, only the cytosine derivative 99 showed weak anti-HIV activity (Scheme 13 and Table 3). An oxidative coupling reaction for synthesizing carbocyclic nucleosides mediated by hypervalent iodine was

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

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

• . In contrast to the thoroughly investigated properties of GalNAc, other stereoisomers have not been probed for biological or pharmaceutical activity, yet. Highly flexible synthetic routes are required to access and probe the entire compound class of 2-amino-2-deoxysugars for further structure–activity

• of the four desired stereogenic centers. By extending compound 5 via a Horner–Wadsworth–Emmons (HWE) reaction [15] and subsequent stereoselective introduction of the corresponding nitrogen functionality, a route to four different 2-amino sugar stereoisomers has been elaborated. Results and Discussion

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• Vorbrüggen coupling reaction [66], the synthesis of C-nucleosides typically gives a mixture of stereoisomers (α and β) at the anomeric carbon [48][49][54][62][67][68]. Since the naturally occurring nucleosides (and most biologically active nucleosides) are β-anomers, achieving 100% stereospecificity in C–C

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• mass spectrum and the retention index match reported data. The comparison of retention indices is particularly important, if different stereoisomers need to be considered, because stereoisomers may have very similar mass spectra, as observed for the sesquiterpenes α-muurolene (3), α-amorphene (4), and

• ; MS (EI, 70 eV) m/z (%): 218 (81) [M]+, 204 (13), 203 (100), 137 (53), 136 (17), 108 (21), 67 (26), 43 (23), 39 (13). Structures of the widespread fungal volatiles oct-1-en-3-ol (1) and 6-pentyl-2H-pyran-2-one (2), the stereoisomers α-muurolene (3), α-amorphene (4) and α-cadinene (5), and the

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide

• catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er. Keywords: kinetic resolution; Michael addition; organocatalysis; pregabalin; squaramide; Introduction Asymmetric organocatalysis has considerably broadened possibilities for

• have measured specific optical rotation for compound 1 to be [α]D20 −2.6 (c 0.95, MeOH). This value corresponds better with literature data, which for the (3R,4R)-isomer states [α]D20 −5.3 whereas for (3R,4S) [α]D20 +14.9. Conclusion We have shown that 4-methylpregabalin stereoisomers can be

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• compounds a synthesis of references was required. For one of the main compounds, 5-hydroxy-4,6-dimethyloctan-3-one, the relative and absolute configuration was determined by synthesis of all eight stereoisomers and gas chromatographic analysis using a homochiral stationary phase. Another identified new

• –Wadsworth–Emmons reaction with triethyl 2-phosphonopropionate (19) yielded ethyl (E)-2,4-dimethylhex-2-enoate (20) as a separable mixture of E and Z stereoisomers (E/Z = 10:1). The purified E diastereomer was reduced with DIBAl-H to the corresponding alcohol 21. A PCC oxidation and addition of

• from an α-cleavage next to the alcohol function. To verify this structural proposal for 11a, racemic 2-methylbutanal (18) was reacted in an aldol addition with the enolate anion of pentan-3-one (23) which produced a racemic mixture of all four diastereomers 11a–d (Scheme 4). All eight stereoisomers of

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• the nucleophile attacking from the open top face seen in 30, forming sole product 26a. If a free carbocation was formed as shown in path A, both stereoisomers 26a and 29 should have been observed, which was not evident. Also, if a free carbocation was formed the product likely would have undergone

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• the nucleophilic agents used in these reactions were usually prepared by reaction of sodium hydride or sodium ethoxide with a proper nucleophile, such as diethylamine, piperidine, pyrrole, ethanol, p-toluenesulfonamide, thiophenol and others. Depending on the reactants used, Z- or E-stereoisomers of

• the products 32 were obtained, but most commonly the reactions resulted in a mixture of stereoisomers (Scheme 22). The yield of the reaction was dependent on the kind of substrate and ranged from 14 to 68% [38]. The reaction involving organocopper compounds as carbon nucleophiles (R2CuLi, where R

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• can be converted into saturated (2-oxohexahydropyrimidin-4-yl)acetic acid derivatives by mild hydrogenation of the endocyclic C=C double bond in the presence of Pd/C as catalyst. The cis-stereoisomers selectively formed upon reduction of the Michael-type products were structurally determined by X-ray

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• diastereomers were studied and used quite extensively [8][10]. So far, however, assignments of configuration to four diastereomeric compounds, i.e., tetrads, were mostly performed by separately comparing selected pairs against each other. However, the availability of multiple stereoisomers should translate to

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• . Crystallographic analysis of the major diastereomer of 3a (some hydrogen atoms are omitted for clarity). Each color represents the following atoms: gray, carbon; white, hydrogen; blue, nitrogen; red, oxygen; green, fluorine; yellow, sulfur. Explanation of the construction of the main stereoisomers. Optimization of

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• dependence, neighboring group assistance and chemodifferentiation. Keywords: amino acids; chemoselectivity; fluorine; functionalization; stereoisomers; Introduction Fluorinated molecules exert an ever-increasing impact in medicinal chemistry thanks to their valuable biological properties. Numerous drugs

• -membered diol stereoisomers (±)-1 and (±)-4 proved to be highly substrate dependent and on the basis of our earlier findings on substrate determinant fluorinations [37], we next investigated the effect of the nature of the N-protecting group on this reaction. The treatment of N-Cbz-protected dihydroxylated

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• revealed the existence of all possible configurations of vicinal hydroxy groups among the 2,3-stereoisomers of castasterone [20]. Minor BS constituents with structural fragments of types 6–8 (Scheme 1) showed reduced growth promoting biological activity when compared to castasterone, thus indicating that

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• tetracyanoethylene (TCNE) with numerous applications [1][2][3], and its role in cycloaddition reactions is of special interest. Dialkyl dicyanofumarates E-1 and dicyanomaleates Z-1 ((E)- and (Z)-butenedioates 1, Figure 1) are less known, but the availability of both stereoisomers is of great advantage for the

• reagent yielded 1-azabicyclo[2.1.1]hexanes 60 as products of an intramolecular cyclization of the intermediate zwitterion 57. In all cases, these products were obtained as mixtures of cis-and trans-stereoisomers in favor of the trans-isomer [59][61]. Another class of nucleophilic reagents used for

• as single stereoisomers (79% yield) [63]. The same reaction pathway was observed in reactions with aromatic 1,2-diamines. For example, starting with benzene-1,2-diamine, the corresponding 2-oxo-1,2,3,4-tetrahydroquinoxaline derivatives, analogous to 73, were obtained in high yields as Z-isomers

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• corresponding adduct 44 in 93% yield. Importantly, both stereoisomers obtained were oxime E,Z-isomers with the C-7 relative configuration being the same as in myrioneurinol. Subsequent deoxygenation and reduction of aldoxime followed by transformation of the malonate unit to the formyl group furnished

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• chirality transmission (CT) on the basis of the chiral HPLC analysis (Table 4, entries 1, 4, and 5). Unanimous formation of (R)-stereoisomers at the 3 position of 7 from (R,E)-6 led to confirmation that the proton attached to C1 was migrated to C3 from its si face, thus from the same back side if (R,E)-6

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• desired (Z,E,Z)-configured triene 19. Again, we did not encounter formation of stereoisomers in the triene unit. The configuration of the triene was unequivocally assigned by analysis of coupling constants (J) and by measuring nuclear Overhauser effects (nOe). Finally, desilylation and global

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• of this chemistry is its ability to provide 1,2-cis glycosides with good stereoselectivity, as these glycosides still remain among the most challenging stereoisomers to synthesize as C2 neighboring group participation is not possible [40]. In fact, the access to 1,2-cis glycosides is considered a