Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• general structure M–O–LG, with a metal and a leaving group connected to an oxygen atom, have been shown to be an excellent electrophilic oxygen source for nucleophilic organometallic species [72]. Since the original discovery of Müller and Töpel of lithiated peroxides [73], several studies have been

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• directly reflected by the observed hydrolysis rate, whereas the changes in polarity of the leaving alcohol do not give marked changes on the rate. The latter is due to the fact that the kinetic effects on the protonation step and the leaving group ability largely cancel each other. In our study, the

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• be the optimum leaving group by thorough investigations on the elimination of sulfide, sulfinyl, and sulfonyl groups at the 2-position of benzothiopyranone. Most 2-aminobenzothiopyranones were obtained in good to excellent yields under refluxing in isopropanol within 36 h. This method is base-free

• -imidazolylbenzothiopyranones [10]. It is well known that the sulfide, sulfinyl and sulfonyl groups are generally used as the leaving group for the synthesis of 2-substituted 4H-chromen-4-ones [11][12][13][14][15][16][17][18][19][20][21][22]. Due to the higher electronegativity of the oxygen atom compared to the sulfur atom

• provided a much higher product yield (Table 2, entries 1, 3 and 5 vs entries 2, 4 and 6, respectively) and sometimes required a shorter reaction time (Table 2, entry 3 vs entry 4) than the corresponding substrate 3a. To further verify the advantage of the sulfinyl group as the optimal leaving group, the

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• riboside. The stereochemical outcomes of the synthesis (anomeric ratio) depends on the nature and the stereochemistry of the leaving group X in sugar B (α- or β-anomer), on the nature of the substituents at the amide nitrogen atom in Nam, and on the conditions of glycosylation, such as solvent and

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• Nucleophilic substitution at silicon is already discussed with SN2 mechanism, following a backside attack opposite of the leaving group, as well as a front side attack near the leaving group [62][63][64][65][66][67][68]. A backside attack at the silicon in dichlorosilane 7 and monochlorosilanol 8 is blocked by

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• (Scheme 1) shows that, in addition to tubugi-1 itself, only the readily accessible building block 4 is required to construct the activated compound tubugi-1-SSPy (3) as a universal precursor for peptide–toxin conjugate syntheses [57]. The pyridyl disulfide is a leaving group which can be substituted by

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

• and faster access to these biologically abundant and relevant α-D-GalpNAc-(1-3)-D-GalpNAc motifs. Undesired migration followed by benzylation of the 3-O-Bz GalN3 using several different benzylation procedures (LG: leaving group). Simple synthesis of two acceptors and two donors from the same common

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

• Clémentine Minozzi,
• Jean-Christophe Grenier-Petel,
• Shawn Parisien-Collette and
• Shawn K. Collins

Beilstein J. Org. Chem. 2018, 14, 2730–2736, doi:10.3762/bjoc.14.251

• amount of the formylated product 3 (Table 2, entry 4). A possible explanation for the increased yield of 3 when using TBAB could be due to slower displacement of leaving group by the “bulkier” source of bromide. In attempting to extend the residence time, the flow rate of the reaction mixture was

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• , we used an aprotic polar solvent like DMF, which weakly solvates the enolates. However, treatment of compound 10 with benzyl bromide and K2CO3 in DMF gave exclusively the C-3 alkylated derivative. Thus, we considered that a hard leaving group such as a sulfonate should play a key role in favouring O

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• versatile leaving group for further transformations. The involvement of the iodine in the radical reactions of styrenes is complicated by the fact that unsaturated compounds readily undergo electrophilic iodination with the addition of an external nucleophile [61][62]. The oxidants used for the preparation

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• different substitution pattern at positions 3, 4 and 5. PG: protective group, X: leaving group. Activation of 7 to oxocarbenium ion 9 in the Ritter reaction. Zemplén deacetylation of 10i. Benzylation of 10j to give 10b. Plausible mechanism of the Ritter reaction. For better clarity C-2 is not shown in

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• carbodiimide-promoted reactions [13][14]. As presented in Figure 2, step a, the first step of a carbodiimide-type conjugation involves the generation of an O-acylisourea intermediate, which is highly electrophilic and which bears the urea-based good leaving group. Such activation of carboxyl groups onto a

Acyl-group specificity of AHL synthases involved in quorum-sensing in Roseobacter group bacteria

• Lisa Ziesche,
• Jan Rinkel,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 1309–1316, doi:10.3762/bjoc.14.112

• by substitution of the good leaving group 5’-deoxy-5’-thiomethyladenosine (5) of the thioester group, leading to homoserine lactone 4 formation (Scheme 1). Recently a LuxI-homolog, BjaI [20] preferring acyl-coenzyme A (CoA) substrates instead of the common ACP precursors, was characterized [21]. The

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

• Gernot A. Eller,
• Gytė Vilkauskaitė,
• Algirdas Šačkus,
• Vytas Martynaitis,
• Ashenafi Damtew Mamuye,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

• -substituents at the pyrazole C4 position, like 5-chloropyrazole-4-carbaldehydes or 4-esters, turned out to be particularly useful due to the easy conversion of the chloro substituent into other functional groups or its nature as a good leaving group in ring-closure reactions. In this respect we were interested

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

• bonds. The subsequent intramolecular substitution reaction of intermediate 61 having hypervalent iodine as a good leaving group yielded the required heterocycles. After Wirth’s report, Nevado et al. discovered a newly modified chiral iodine reagent 13 analogous to lactate-based chiral iodoarenes [53

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent

• Elsa Deruer,
• Vincent Hamel,
• Samuel Blais and
• Sylvain Canesi

Beilstein J. Org. Chem. 2018, 14, 1203–1207, doi:10.3762/bjoc.14.101

• , decarboxylation, and fragmentation [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The sulfonate group is a useful functionality frequently employed as a leaving group in substitution reactions. Production of sulfonates [28] from alcohols generally involves reaction with a

• diol derivative containing a linear chain in only one step. One alcohol is available as a leaving group and the second is protected by conversion into a trichloroacetate moiety (Scheme 4). Conclusion A novel oxidative method for producing sulfonates from sulfinates using hypervalent iodine reagents has

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

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• leaving groups that are less basic than EtO−, such as 5´-O− of nucleoside, the lifetime expectedly is shorter. If the leaving group is very good, such as an aryl group, a synchronous concerted mechanism (ANDN) may take over the stepwise mechanism (AN + DN). Model compounds and experimental tools Studies

• been done with this simple model. One should, however, bear in mind that the p-nitrophenoxy group is a 108 times better leaving group than a 5´-linked nucleoside and, hence, the rate limiting step of these two reactions can well be different, as discussed later in more detail below. In addition, the

• underlying idea behind the latter application is that protonation of the leaving group by a general acid is not needed with 5´-thiosubstituted analogs, since the sulfide ion is a much better leaving group than the alkoxide ion. Most extensively used thiosubstitution, however, is replacement of either one of

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

• cleavage proceeds either by activation of a nucleophile that attacks C1' or by stabilization of the leaving group, which could either be the nucleobase or an oxocarbenium ion [31][36]. As such, the oxocarbenium ion is a species formed during the glycosidic bond cleavage, which may be present as an

• acids. Shown is the monomeric building block of nucleic acids. Changes to the nucleotide structure can affect molecular recognition, as well as structure and function. Formation of oxocarbenium ion during glycosidic bond cleavage in nucleosides [31]. The extent of leaving group stabilization and

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• intermediate. The functionalities required for the secondary transformations like the leaving group (-Cl) for nucleophilic substitution, alkyne and azide for IAAC can be assembled via the Ugi reaction (Scheme 1). Results and Discussion We initiated our studies with the Ugi 4-component reaction of o

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• terminal hydroxy group of the primer has to attack the activated 5'-phosphate of the primer, most likely producing a pentavalent intermediate. Unless the leaving group finds itself in the proper apical position of the intermediate, this is followed by pseudorotation and then the release of the leaving

• the methyl group at the 5-position of the pyrimidine ring, shielded the leaving group-bearing phosphate from incoming water from some angles of attack. For OAt esters of ribonucleotides, we also measured the rates of hydrolysis at 0 °C and −20 °C, and the detailed data can be found in Supplementary

• neutral pH, i.e., conditions favoring longevity for this type of activated monomer, which requires protonation of the imidazole ring to be turned it into a good leaving group. Binding equilibria As mentioned above, primer extension involves the binding of the incoming nucleotide to the primer–template

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• protected (typically peracetylated) GlcNAc or other 2-acetamido sugar [37][38][39][40]. Oxazoline formation is achieved by activation of the leaving group at the anomeric centre and neighbouring group participation by the 2-acetamide. Unfortunately application of these reaction conditions to oligosaccharide

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• -iodoaniline 32 in 68% yield after isolation [52]. The cyclization was performed via nucleophilic aromatic substitution with DBU and DABCO. Presumably DABCO activates the chlorine and modifies it into a better leaving group allowing the sterically hindered base DBU to abstract a proton from the protected

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• years, there has been an increasing interest in C–F bond activation [2], with a view to using organic bound fluoride as a leaving group in substitution reactions that typically require more activated leaving groups. Such an approach could circumvent the requirement for protecting groups in multistep

• , benzylic substitutions would be expected to display a significant level of SN1 character. However, given the particularly poor properties of fluoride as a leaving group, developing a better understanding of the dissociative nature of these transformations remains of considerable interest. A direct

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• strategies have been reported which mostly rely on the same principle: One of the two nucleotides (typically the monophosphorylated nucleotide) is equipped with a good leaving group while the other one acts as a nucleophile. Different leaving groups have been exploited for the synthesis of cap analogues