Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• are biosynthesised in seven principal ways (Scheme 2). Those comprise nucleophilic addition of a hydroxy group to electrophiles like epoxides 4, carbonyl groups 6 or Michael acceptors 9, potentially followed by further processing (a–c in Scheme 2). Lactones 12 are formed by transacylation of a

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• the enantioselective reduction of α-substituted conjugate addition acceptors, including catalytic hydrogenation, multiple reviews have already appeared on this topic, and therefore asymmetric catalytic reduction will not be covered here [11][12][13]. Conjugate addition followed by terminal

• high yield and enantioselectivity for both α-alkyl and α-aryl conjugate addition acceptors. Alkyl substrates reacted smoothly at 25 °C (90–98% yield, 90:10 to 95.5-4.5 er) even when R was a more sterically demanding isopropyl or cyclohexyl group. Aryl substrates required lower reaction temperatures and

• additions to other classes of Michael acceptors only being reported more recently. While many examples using sulfur and carbon nucleophiles have been reported, the addition of other heteroatom nucleophiles remains relatively unexplored. This approach for the synthesis of tertiary carbon stereocenters

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• groups [38][39][40][41][42][43], is based on a sequential nucleophilic addition and an intramolecular allylic substitution reaction. It relies on the coupling of different homoallylic nucleophiles of general type 6 to diverse electrophiles 7 such as Michael acceptors, or heteroolefins as for example

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• acceptors in reactions promoted by bifunctional Brønsted bases. 1.2.1 Nitroalkenes as acceptors. Investigation of the base-catalyzed Michael addition reaction of 2-thio-1H-imidazol-4(5H)-ones 4 to nitroalkenes 5 [55] revealed that cinchona alkaloids such as quinine, (DHQ)2Pyr or even thiourea tertiary amine

• doesn’t change after the addition of nitrostyrene. 1.2.2 α-Silyloxyenones as acceptors. Among Michael acceptors, simple α,β-unsaturated esters and amides still are challenging substrates in direct Michael additions and have only been employed in few successful Michael reactions, mainly due to their

• efficient platforms for bidentate coordination in metal catalysis and good precursors of carboxylic acids, ketones and aldehydes upon oxidative cleavage of the keto/diol moiety [72]. More recently, a comprehensive study on the first evidence of the utility of these acceptors in organocatalysis has been

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• they can be immediately employed as glycosyl acceptors or readily converted into glycosyl donors. Research in this way is now in progress in our laboratory. Examples of deoxofluorinated hexosamines. Retrosynthetic plan. Preparation of starting 2-azido compounds. Reagents and conditions: (a) NaN3, NH4Cl

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• with heteroaryl chlorides 92 and 94 to obtain products 93 and 95 in 84% and 35% yield, respectively [66]. These results represent a breakthrough in the direct α-C–H functionalization of piperazines. The generation and trapping of the α-amino radical derived from 87 with radical acceptors under mild

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• acetylated glycosyl bromides 13, 15–20 derived from pyranoses, furanoses and a disaccharide (Figure 2) were prepared as glycosyl donors in one step and high yields starting from the peracetylated sugars. The glycosyl bromides depicted in Figure 2 were subsequently examined in the glycosylation of acceptors

• was selected for the glucosylation reactions of acceptors 6a and 6c with bromide 13, affording compounds 21a and 21c with full β-selectivity. Acetylated tyrosol 9 as glycosyl acceptor reacted only smoothly with 13 under all three studied reaction conditions (Table 1, entries 7–9) affording the

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• (Figure 1). Some examples of these properties are rigidity, disposition of the two stereogenic centers, ability of the hydroxy and amino groups to coordinate to some metals or to act as hydrogen-bond donors/acceptors, the different catalytic activity of these chemical groups and their possible

• -bonding acceptors in their activation through hydrogen-bonding catalysis. The corresponding final esters or amides are obtained after proper treatment of the reaction mixture. During the screening of catalysts, the best enantioselectivity (74% ee) was obtained using ent-4 in the addition of indole (2a) to

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• rings initiated by oxy/aza/sulfa-Michael addition In 2007, Wang and co-workers utilized 2-mercaptobenzaldehydes 163 and α,β-unsaturated systems as Michael acceptors, such as α,β-unsaturated oxazolidinones 164 and maleimides 52, in order to catalyze Michael aldol cascades to construct versatile

• ) pathway of a Michael–retro-Michael–Michael–Michael reaction. The same year Zhao and co-workers reported a novel domino Michael–Knoevenagel reaction between 2-mercaptobenzaldehydes 163 and easily accessible Michael acceptors 169 catalyzed by 9-epi-aminoquinine thiourea 57 (Scheme 55) [76]. Various adducts

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• against a variety of bacterial strains, in line with a simulated enthalpic penalty of +8.8 kJ/mol. It has been suggested by Palumbo Piccionello et al., that, though the 1,2,4-oxadiazole ring is isosteric with the oxazolidinone ring and possesses similar hydrogen bond acceptors sites, the lack of

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• -ketophosphonates [21][22], fluoromethyl ketones [23][24] and isatins [25][26]. Despite these significant advances described above, the use of more challenging ketones with heterocyclic structures as Henry acceptors has remained relatively less explored. In this context, developing a new Henry reaction for the

• work represents the first example of 1H-pyrrole-2,3-diones used as Henry acceptors for the asymmetric reaction. Herein, we report our preliminary results on this subject. Results and Discussion We started our studies with the reaction of ethyl 1-benzyl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrole-3

N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd–NHC complexes: synthesis, characterization and catalytic activity in carbon–carbon bond-forming reactions

• Senem Akkoç,
• Yetkin Gök,
• İlhan Özer İlhan and
• Veysel Kayser

Beilstein J. Org. Chem. 2016, 12, 81–88, doi:10.3762/bjoc.12.9

• ][10][11]. This is because NHC complexes are easily obtained by deprotonating imidazolium or benzimidazolium salts and most are relatively stable in air and moisture. They are weak π-acceptors and strong σ-donors and can form strong M–C bonds with transition metal ions compared to trivalent phosphine

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• extend the annulation reaction to phenols with other Michael acceptors at the ortho-position (such as unsaturated esters, enals and nitroolefins) were not successful. Additionally, a very low yield (ca. 10%) of the product 8aa was obtained when the chalcone formation (7a) and its annulation reaction with

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• nucleophile and relatively unreactive Michael acceptors [27][28][29][30][31][32][33]. We envisioned that our recently developed powerful hydrogen bond (HB)-donor bifunctional organocatalyst [33] could promote the desired reaction of 7 or 8, which can be synthesized from commercial sources 9 or 10. Overall

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• general for a variety of nitroalkene Michael acceptors and nitroacetate donors. For this reason, we initially studied the reaction using squaramide 4 as catalyst that leads to the formation of syn-3 adducts. In this sense, and as it can be seen in Table 1, the reaction performed excellently in almost all

• the cases studied. In particular, when the reaction was conducted using nitrostyrene derivatives as Michael acceptors, the corresponding adducts 3a–k were isolated cleanly, in high yields, diastereo- and enantioselectivities regardless the electronic nature of the aromatic substituent of the

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• Chimie, 8 Rue de l’Ecole Normale, 34296 Montpellier Cedex 5, France 10.3762/bjoc.11.263 Abstract The copper-catalyzed asymmetric conjugate addition (ACA) of nucleophiles onto polyenic Michael acceptors represents an attractive and powerful methodology for the synthesis of relevant chiral molecules, as

• it enables in a straightforward manner the sequential generation of two or more stereogenic centers. In the last decade, various chiral copper-based catalysts were evaluated in combination with different nucleophiles and Michael acceptors, and have unambiguously demonstrated their usefulness in the

• control of the regio- and enantioselectivity of the addition. The aim of this review is to report recent breakthroughs achieved in this challenging field. Keywords: conjugate additions; electron-deficient alkenes; enantioselective catalysis; extended Michael acceptors; organometallic nucleophiles

Urethane tetrathiafulvalene derivatives: synthesis, self-assembly and electrochemical properties

• Xiang Sun,
• Guoqiao Lai,
• Zhifang Li,
• Yuwen Ma,
• Xiao Yuan,
• Yongjia Shen and
• Chengyun Wang

Beilstein J. Org. Chem. 2015, 11, 2343–2349, doi:10.3762/bjoc.11.255

• the fields of supramolecular and materials chemistry due to their great potential application in molecular electronics, for example, as switches and conductors [10][11][12][13][14]. As we all know, TTF derivatives can form charge transfer (CT) complexes with electron acceptors such as

Cu(I)-catalyzed N,N’-diarylation of natural diamines and polyamines with aryl iodides

• Svetlana P. Panchenko,
• Alexei D. Averin,
• Maksim V. Anokhin,
• Olga A. Maloshitskaya and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2015, 11, 2297–2305, doi:10.3762/bjoc.11.250

• to the conditions of chromatographic isolation in each case. 4-Iodoanisole with a strong electron-donating substituent provided 56% yield of the diarylated compound 17 (Table 2, entry 5), while one could expect much lower reactivity of this compound compared to aryl iodides bearing acceptors

Photoinduced 1,2,3,4-tetrahydropyridine ring conversions

• Baiba Turovska,
• Henning Lund,
• Viesturs Lūsis,
• Anna Lielpētere,
• Edvards Liepiņš,
• Sergejs Beljakovs,
• Inguna Goba and
• Jānis Stradiņš

Beilstein J. Org. Chem. 2015, 11, 2166–2170, doi:10.3762/bjoc.11.234

• corresponding ground state species. The reaction between photochemically generated radical cations and radical anions by electron transfer from photoexcited electron donor to electron acceptors is often reversible [37] thus reproducing the reactant pair without the formation of a chemical bond. As the dioxygen

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• interactions point of view the most efficient association exists in complexes in which all hydrogen bond donors belong to one molecule and all hydrogen bond acceptors to the other. The last condition was tested for quadruple hydrogen bonded associates [14], while the basis of this phenomenon are secondary

• to exist in linear form without any intramolecular HBs and stabilized by four intermolecular ones. In general the dibutyltriuret molecule carrying four hydrogen bond donors (D, red, Figure 2) and three hydrogen bond acceptors (A, blue) can exist in various conformations stabilized by one or two

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• hydrogen bonding acceptors. 1H NMR and fluorescence experiments in chloroform showed that this series of foldamers complexes primary and secondary alkyl ammonium products [39]. In most cases, we investigated the binding of foldamers for different guests in less polar chloroform. However, during the

• environments [46]. The high stability of the folded conformation of the 22 series also make them useful frameworks for creating a variety of complicated supramolecular architectures [42]. Although alkoxyl groups had been popularly used as acceptors for intramolecular hydrogen bonding [40][41][42], I was also

• approximately 1.8 nm in diameter [69]. At first we expected that this series of triazole foldamers would be good hydrogen bonding acceptors. Intriguingly, the foldamers did not exhibit observable binding affinity to saccharides or amide derivatives even in less polar chloroform. Liyan designed different

Chiral Cu(II)-catalyzed enantioselective β-borylation of α,β-unsaturated nitriles in water

• Lei Zhu,
• Taku Kitanosono,
• Pengyu Xu and
• Shū Kobayashi

Beilstein J. Org. Chem. 2015, 11, 2007–2011, doi:10.3762/bjoc.11.217

• catalysis, which has been reported recently for asymmetric boron conjugate addition, is characterized by the effective and thermodynamically stable catalysis in water. Furthermore, a broad range of α,β-unsaturated acceptors, including one example of an α,β-unsaturated nitrile, are applicable, and the

Engineering Pichia pastoris for improved NADH regeneration: A novel chassis strain for whole-cell catalysis

• Martina Geier,
• Christoph Brandner,
• Gernot A. Strohmeier,
• Mélanie Hall,
• Franz S. Hartner and
• Anton Glieder

Beilstein J. Org. Chem. 2015, 11, 1741–1748, doi:10.3762/bjoc.11.190

• cofactors as electron donors and acceptors. As these cofactors are required in stoichiometric amounts to drive the reaction to completion and the simple addition of these compounds is not acceptable from an economical point of view, efficient in situ regeneration of the consumed cofactor is required. During

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• , cyclic amines were produced. Carboxylic acids were particularly fruitful affording C-centered radicals that alkylated alkenes and took part in tandem addition cyclizations producing chromenopyrroles; decarboxylative homo-dimerizations were also observed. Acceptors initially yielding radical anions

• -affirmed as the best compromise. Reactions of aryloxyacetic acids functionalized with suitably sited alkene 24, aromatic or oxime ether acceptors, were carried out with P25 under standard conditions and also in sol–gel TiO2 coated NMR tubes (see Scheme 6). For styrenyl acids 24 control photolyses in the

• series of two electron reductions. The scope of reductive photoredox applications was significantly boosted by Scaiano and co-workers’ discovery that organic halides function as acceptors with platinized TiO2 nanoparticles [71]. They used (iPr)2NEt as the sacrificial donor and demonstrated that reductive

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• unknown [7]. In general, GTs transfer sugar nucleotide donors onto suitable acceptors during the biosynthesis of glycans and glycoconjugates [8]. Both donor and acceptor substrates are recognized by GTs binding pockets. For instance, in the course of biosynthesis of complex and hybrid oligosaccharides