(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

• values the nature of R3 is very important. The better the leaving group R3 is, the higher the values of the ee. It is mentioned that the ee in this reaction is up to 96%, and the recommended R3 group to be used is 3,4,5-trifluorobenzyl. The use of the bifunctional amine-thiourea catalyst 27, into a

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• nucleophile and then as a leaving group in cyanide-catalysed benzoin reactions [8]. Analogously, Breslow invoked the generation of a nucleophilic thiazolylidene species 1 via deprotonation of the thiazolium salt by base. The ylide 1 may also be represented as its resonance structure 1’ (carbene). Nucleophilic

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• solvolysis of syn- and anti-norborn-2-en-7-ylmethyl-X diastereomers (Is and Ia, Figure 6; X is a leaving group) both led to the same two products, but in different ratios, despite sharing a common intermediate (in different conformations; V, Figure 6) [59]. The major product generated from the solvolysis of

• magnitude varied with leaving group identity) was ascribed to a “memory effect”. Put simply, product ratios were skewed from what would be expected by simply comparing activation barriers, because the reacting molecule “remembers” the conformation from which it came; this is a hallmark of dynamic matching

• in order to make the products; consequently, dynamics trajectories were initiated from the regions of these TSSs (using a lower level of theory so that 250 trajectories from each transition state could be obtained in a reasonable amount of time; the influence of the leaving group on dynamical

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• molecule and reagent or between host and guest in cases 1) and, usually, 2), reaction type 3) requires a CD derivative that bears a good leaving group and the complexation phenomenon can be disadvantageous here. While type 1) can eliminate usually the less problematic solvents only, the application of BM

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• organophosphorus (NOPs) share a typical structure with a pentavalent phosphorus atom linked to a leaving group (LG), two substituents (R1 and R2) and an oxygen or a sulfur atom (Figure 1), explaining the wide structural diversity of organophosphates. They can be classified into three categories depending on the

• nature of the leaving group. The first one includes the least toxic compounds used as pesticides; the second one corresponds to the G agents developed as chemical warfare agents and the third one to the dreadful V agents group (Figure 2). Due to their use in agriculture, organophosphate accidental or

• the P(R)-isomers into the CD cavity is followed by the formation of a hydrogen bond between a C-3 hydroxy and the phosphoryl oxygen atom of soman. Then a C-2 ionized hydroxy function attacks the phosphorus atom to form a covalent bond with the release of the leaving group (fluoride ion). The different

Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

• Javier Ajenjo,
• Martin Greenhall,
• Camillo Zarantonello and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 192–197, doi:10.3762/bjoc.12.21

• the use of liquid ammonia as a co-solvent (Table 2, entry 5). For direct amination 1,1,1-trimethylhydrazinium iodide was used, which upon deprotonation with strong base provided the nitrogen nucleophile containing the leaving group (Me3N) (Table 2, entry 6). High regioselectivities were observed in

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• cyclononenes in a stereospecific manner [27]. The relative configuration of the leaving group (LG = OTs, OMs, Hal, NR3+) and the adjacent substituent determine the E/Z-geometry of the olefin. A cis-geometry leads to the formation of the E-configured double bond. In general, the Grob fragmentation is the most

• conditions [48] and an ensuing desilylation furnished a diol. In order to introduce a leaving group for the following key step, the secondary hydroxy group was tosylated to afford 79. Once again, a stereospecific Grob fragmentation of tosylate 79 served as the key step for the synthesis of the

Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

• Emeline Rideau and
• Stephen P. Fletcher

Beilstein J. Org. Chem. 2015, 11, 2435–2443, doi:10.3762/bjoc.11.264

• is formed in a completely non-selective pathway. In the case of allyl phosphate 2d, the system appears to lack reactivity and the reaction quickly dies, so that 10 (Figure 3) is formed with poor conversion, and we speculate that the phosphate leaving group inhibits the catalyst which would explain

Coupling of α,α-difluoro-substituted organozinc reagents with 1-bromoalkynes

• Artem A. Zemtsov,
• Alexander D. Volodin,
• Vitalij V. Levin,
• Marina I. Struchkova and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2015, 11, 2145–2149, doi:10.3762/bjoc.11.231

• nitrostryrenes (with the NO2 serving as a leaving group) [20], were employed. Herein, we report that 1-bromoalkynes, which are known to be involved in reactions with various organometallic compounds [22][23][24][25][26][27], can be used as suitable coupling partners for difluorinated organozinc compounds 2. This

A comprehensive study of olefin metathesis catalyzed by Ru-based catalysts

• Albert Poater and
• Luigi Cavallo

Beilstein J. Org. Chem. 2015, 11, 1767–1780, doi:10.3762/bjoc.11.192

• pyridine groups, but the function of both chemical groups is the same. The release of a pyridine or phosphine group generates a 14-electron (14e) species, which binds to an olefin, coordinated cis to the alkylidene. The exchange of the leaving group by an olefin is found to be mainly dissociative [4][27

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• and concluded that removal of the leaving group, water, to draw the equilibrium towards polymerization, and the reversal nature of lipase catalysis are two main obstacles. Others have pointed out the latter also [54]. Often a two-step procedure has been used, an initial polymerization to achieve

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• amide in the presence of acid was discovered in 1886. This rearrangement involves the migration of a group anti to the leaving group on the nitrogen atom. The BR has widely been used in synthetic organic chemistry, for example, a large-scale production of Nylon-6 is based on the synthesis of ε

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• acids are known to undergo acid and alkaline hydrolysis at rates 105–108 times faster than their acyclic analogs [17]. Thus, cyclic esters may be regarded as a halogen equivalent in terms of their leaving group ability under nucleophilic displacement conditions [18]. The rapid hydrolysis of 2-methoxy

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• buffer conditions were chosen to be as close as possible to the conditions used for β-glucocerebrosidase activation assays (Gaucher disease) which are based on a fluorescent leaving group (4-methylumbelliferone) allowing fluorescence recording after reaction quenching at pH 10.7 [64]. The BODIPY-based

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• -chloroacetyl groups on C-7 and C-8 for better α-stereoselectivity [12] produced 3. An α-anomeric phosphate leaving group was chosen since it had previously shown high reactivity [14][18] and selectivity [15]. Building block 4 was obtained in 54% yield over three steps from 1. “Approved building blocks” for

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• with the N,N’-ditolylcarbodiimide, although the starting material was consumed. The mechanism proposed by Ispikoudi et al. [33] proposes the amine moiety as a leaving group during this process. Anilines (R = tolyl) are worse leaving groups than alkylamines (R = iPr, C6H11), thus providing a likely

The preparation of new functionalized [2.2]paracyclophane derivatives with N-containing functional groups

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 437–445, doi:10.3762/bjoc.11.50

• tetrahedral intermediate thus generated, the polyether bridge functions as a leaving group to form an aldehyde intermediate. This is subsequently reduced a second time to the N-CH3 moiety. In compound 22 one formyl group is still present whereas in 23 this has been lost completely. Both compounds were

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

• Aneta M. Tomkiel,
• Adam Biedrzycki,
• Jolanta Płoszyńska,
• Dorota Naróg,
• Andrzej Sobkowiak and
• Jacek W. Morzycki

Beilstein J. Org. Chem. 2015, 11, 162–168, doi:10.3762/bjoc.11.16

• the two, the latter appeared to be much more efficient in cholesteryl transfer to the sugar moiety. The problem, however, with 6β-steroidal thioethers is that they are not easily accessible. Therefore, we searched for the best leaving group at C-3. A series of cholesterol derivatives was tested and

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes

• Yibiao Li,
• Liang Cheng,
• Xiaohang Liu,
• Bin Li and
• Ning Sun

Beilstein J. Org. Chem. 2014, 10, 2886–2891, doi:10.3762/bjoc.10.305

• )ethynyl)benzene were performed, as shown in Scheme 4. In F/Br-substituted 1-bromo-2-(2-(2-fluorophenyl)ethynyl)benzene, the fluoro moiety served as leaving group and gave 2-(2-bromophenyl)benzofuran (2t) as a major product. In F/Cl-substituted 1-chloro-2-(2-(2-fluorophenyl)ethynyl)benzene was able to

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• . The reaction of 10 with the second equivalent of PhSeCl leads to selenonium ion 11; once the diphenyl diselenide leaving group is formed, the addition of chloride counter-anions from both directions is accompanied by the formation of [2.3.2](1,2,4)cyclophane derivatives 2 and 3. Most probably compound

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• to be disadvantageous. The recent candidates are based on a pHP motif. Phosphate esters of 10, 14, 24, and acetate 27 [19] each possess a hydroxy donor coupled with an acetyl function bearing the leaving group (Figure 3). One of these, the 5-hydroxy-1-naphthylacetyl motif as its acetate ester 27, has

• favored by aqueous-based solvents that serve both as a proton donor and an acceptor to the conjugate base generated from the chromophore’s triplet state heterolytic cleavage of the leaving group. The dual behavior of H2O is manifest in accepting a proton from the naphthol OH while simultaneously solvating

• overall conversion to released substrate. The formation of competing chromophoric byproducts limits the conversion and yields [6][10][11][15]. For example, changing the leaving group for 10, i.e., photolysis of 6-hydroxy-2-naphthylacetyl GABA ester (Figure 2B) inefficiently released 4-aminobutyrate (GABA

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• -tagged catalyst 1 starting from doubly-protected hydroxyproline 6 [57] is depicted in Scheme 3. To introduce a suitable leaving group for the following step of the synthesis, compound 6 was mesylated to give the derivative 7 [58] for which crystals suitable for X-ray analysis have been obtained (Figure 2

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

• of 1° and 2° alcohols underwent reaction with Bt-OTs giving good to excellent yields of 1-alkoxy-1H-benzotriazoles. Some notable results are as follows. Despite the leaving group ability of BtO−, elimination to styrene does not appear to be a significant problem in the reactions with the isomeric

• , respectively. We next assessed the leaving group ability of the benzotriazolyloxy group. Although carboxylic acid esters of benzotriazole react efficiently with nucleophiles, this is mechanistically distinct from direct displacement. Thus, four of the 1-alkoxy-1H-benzotriazoles (three 1° and one 2°) were

• -azidoethyl)benzene, as assessed by 1H NMR. However, this reaction was incomplete and about 12% of 1f remained unreacted. Nevertheless, these results indicate the leaving group ability of BtO− from benzylic sp3 carbon centers and are interesting in the context of the previously unknown reactivity of this

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• attributed in part to the missing α-orientated 4-alkoxy substituent present in sanfetrinem (113), which may act as a potential leaving group and appears to be crucial for activity [97]. Anthoplalone (1999) Isolated from the Okinawan actinian Anthopleura pacifica, anthoplalone (8) is a secosesquiterpene with

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

• in 5-chloropyrazole-4-aldehydes is sufficiently activated to act as the leaving group in such kind of C–C linkages [17]. Indeed, reaction of chloroaldehyde 2 with different alkynes 3a–c under typical Sonogashira reaction conditions afforded the corresponding cross-coupling products 4a–c in good