Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• building blocks for discovery chemistry programmes. The synthesis starts from a Birch reduction of benzonitrile, followed by an in situ methyl iodide quench. The resultant 2,5-cyclohexadiene was progressed via double epoxidations and then hydrofluorination ring opening reactions. The resultant fluorohydrin

• reduction on benzoic acid, quenching with methyl iodide, and then subsequent conversion of the cyclohexadiene product to a tetrafluorocycloheane motif [11]. The methyl group was a design feature to block hydrogen fluoride elimination from the position alpha to the aldehyde. The diastereoisomers of all cis

• -tetrafluorocyclohexane aldehydes 4 were used successfully in Ugi multicomponent reactions [11][12]. In this paper we report the preparation of amines of this series starting from a Birch reduction on benzonitrile, and with a similar methyl iodide quench, to generate amines 5, which are stable to hydrogen fluoride

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• atom of the betaine; in contrast to other 1,2,4-triazolium-3-aminides [21][23], methylation with methyl iodide was not successful. Salt 9b forms colorless hygroscopic crystals which assume an orange surface color when exposed to air for some minutes. The structures of 1,2,4-triazolium salts 8b and 9b

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• basic conditions using methyl iodide in 32% yield over three steps [41]. Next, TMSOTf activation of fucosyl trichloroacetimidate 8 (Scheme 1) catalyzed the glycosylation of methyl uronate 48 to afford pentasaccharide 49 exclusively as the α-isomer by virtue of remote participation of the 3-O-acetate

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• instability in our system was likely resulting both from the more reactive methyl aglycon and the more reactive fucose carbohydrate part, in analogy to the differences in reactivity of related thioglycosides [37]. Next, the free hydroxy group was methylated using methyl iodide to give derivative 6 in 67

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• carbon of the pendant group precursors, with yields of 61% (9), 82% (10) and 65% (12), respectively. Methylation of bipyridyl intermediate 10 by methyl iodide produced viologen derivative 11 after exchanging the iodide for the PF6− anion. For the methylation step drying of both the reactants 10 and

• methyl iodide and the solvent was essential, since its omission resulted in polymerization of the viologen-pyEDOT, as indicated by 1H NMR (see Supporting Information File 1, Figure S11). We suspect that the polymerization was triggered by the acid generated from methyl iodide reacting with water

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• or O-nonaflation led to functionalized pyridine derivatives. Scheme 1 illustrates this sequence with the synthesis of two 2,2´-bipyridine derivatives 4a or 5b that were obtained by employing picolinic acid chloride for the N-acylations followed by O-methylation with methyl iodide or by O-nonaflation

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• -catalyzed decarboxylative strategies [47]. Results and Discussion We decided to use iodine as an oxidant for the synthesis of 2-oxindoles [48][49][50][51][52][53], starting from β-N-arylamido ester 3a and methyl iodide as the substrates (Table 1). An elaborate optimization study suggested that the

• methylation can be done in the presence of 1.2 equivalents of KOt-Bu and 1.1 equivalents of methyl iodide. This was accompanied with an oxidative coupling using 1.2 equivalents of KOt-Bu and iodine to afford the desired product in 65% yield (Table 1, entries 1 and 2). Optimization studies in search of

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• quaternary ammonium group attached to the NHC ligand (Figure 2) [43][44][45][46][47]. These, now commercially available [48], complexes were synthesised by on-site quarternisation of catalysts containing a tertiary amine functional group with the use of either methyl chloride or methyl iodide. This simple

Robust bifunctional aluminium–salen catalysts for the preparation of cyclic carbonates from carbon dioxide and epoxides

• Yuri A. Rulev,
• Zalina Gugkaeva,
• Victor I. Maleev,
• Michael North and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2015, 11, 1614–1623, doi:10.3762/bjoc.11.176

• [30]. Ligand 7 was efficiently alkylated under mild reaction conditions using either methyl iodide or benzyl bromide, giving the corresponding positively charged salen ligands 8a and 8b in 95 and 78% yields respectively. The aluminium–salen complexes were prepared by treating 8a and 8b with

• . 5,5'-((1E,1'E)-((1R,2R)-Cyclohexane-1,2-diylbis(azanylylidene))bis(methanylylidene))bis(3-(tert-butyl)-4-hydroxy-N,N,N-trimethylbenzenaminium iodide) (8a) To a solution of 7 (100 mg, 0.192 mmol) in dry acetonitrile (5 mL) was added methyl iodide (271 mg, 1.92 mmol). The solution was stirred at room

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• , desmethylmianserin (10) was obtained in 81% yield by reduction of the carbonyl groups using a 1.0 M solution of lithium aluminum hydride in THF. Finally, the reaction between derivative 10 and methyl iodide led to optical pure (S)-(+)-mianserin (1) (as confirmed by chiral HPLC) in 67% yield. In order to obtain

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• an iodine mediated aromatisation, followed by high temperature mono-methylation using dimethyl carbonate/dimethylimidazole as a more benign alternative to methyl iodide at scale. The subsequent Claisen condensation step between ketone 112 and diethyl oxalate (113) was reportedly hampered by product

Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.0^2,6]undeca-3,11-dione and its congeners via ring-closing metathesis

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Rashid Ali

Beilstein J. Org. Chem. 2015, 11, 1123–1128, doi:10.3762/bjoc.11.126

•  2). The structure of the diindole 8 has been established on the basis of 1H NMR and 13C NMR spectral data. The presence of 12 signals in the 13C NMR spectrum clearly indicated that the Cs-symmetry is present in molecule 8. Later, the diindole derivative was treated with methyl iodide in the presence

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• complex alkylating agents can be successfully used in place of methyl iodide. For example, functionalised ethylene glycol oligomers have been used in the preparation of rotaxanes and pseudorotaxanes [28][41][42][45]. Although CsOH·H2O is most commonly used, other bases are also known to remove the

• a common, protected MPTTF intermediate, such as 4a, 4b or 4e, in large quantities, particularly in light of the good stability of the cyanoethyl and tosyl protecting groups. As a simple example of this protocol, it has previously been shown that caesium hydroxide monohydrate (CsOH·H2O) and methyl

• iodide can be used to accomplish the transformation of 2-cyanoethyl thioethers to methyl thioethers in high yield for both TTFs [38] and MPTTFs [25]. Thus deprotection and alkylation are achieved in a single synthetic step (e.g. the preparation of 4h from 4a in Scheme 4). Furthermore, when R1 and R2 are

Quarternization of 3-azido-1-propyne oligomers obtained by copper(I)-catalyzed azide–alkyne cycloaddition polymerization

• Shun Nakano,
• Akihito Hashidzume and
• Takahiro Sato

Beilstein J. Org. Chem. 2015, 11, 1037–1042, doi:10.3762/bjoc.11.116

• –alkyne cycloaddition (CuAAC) polymerization, were quarternized quantitatively with methyl iodide in sulfolane at 60 °C to obtain soluble oligomers. The conformation of the quarternized oligoAP in dilute DMSO-d6 solution was examined by pulse-field-gradient spin-echo NMR based on the touched bead model

• . Keywords: 3-azido-1-propyne oligomer; CuAAC polymerization; hydrodynamic radius; methyl iodide; pulse-field-gradient spin-echo NMR; quarternization; Introduction The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) efficiently yields 1,4-disubstituted-1,2,3-triazole from rather stable azides and

• the quarternized AP oligomer may be applied as a polymeric ionic liquid or a precursor of polymeric ionic liquids. In this study, we investigate quarternization of an AP oligomer with methyl iodide to obtain a soluble oligomer (Scheme 1b) and characterize the quarternized oligomer in dilute solutions

DBU-promoted carboxylative cyclization of o-hydroxy- and o-acetamidoacetophenone

• Wen-Zhen Zhang,
• Si Liu and
• Xiao-Bing Lu

Beilstein J. Org. Chem. 2015, 11, 906–912, doi:10.3762/bjoc.11.102

• [27]. After a proton shift from the enol to nitrogen, the resultant intermediate III is carboxylated with carbon dioxide in the presence of DBU to afford intermediate IV, which subsequently undergoes a cyclization reaction to give V. The product is obtained after derivatization with methyl iodide

Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates

• Qinggang Mei,
• Chun Wang,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 288–293, doi:10.3762/bjoc.11.33

• ) and 3,7-di-O-methylkaempferol (7) Kaempferol was acetylated to furnish the peracetylated derivative 1. Jurd found that with excess of methyl iodide and potassium carbonate in dry acetone, only the 7-O-acetyl group of quercetin pentaacetate is replaced [25]. For the synthesis of 7-O-methylkaempferol (4

• ), we first adopted Jurd’s method. Under similar conditions, however, a mixture of 7-O-, 4′-O- and 4′,7-di-O-methylkaempferol was obtained whether methyl iodide or dimethyl sulfate was used as methylating reagent. Separation of 7- and 4′-mono isomers from the crude product involved tedious and laborious

Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• methyl iodide. Final aromatisation through E2 or the anionic equivalent of the Chugaev reaction are also both viable. As neutral Chugaev reactions normally require very high temperatures this alternative approach is attractive as only moderate temperatures are required (60–80 °C). This procedure allows

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

• methyl iodide afforded adduct 177 with excellent selectivity (dr > 95:5) (Scheme 22). Ozonolysis with reductive work-up and ensuing protection of the formed hydroxy group as TPDPS ether provided lactone 178. Addition of the enolate of tert-butyl acetate to 178 and ketal formation afforded 179. Reduction

A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

• Martin Popr,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142

• from the reaction mixture by vacuum distillation. Pure intermediate 9 was then obtained in 93% yield by simple precipitation of the reaction mixture from propan-1-ol. In the final step, 9 was quaternized by methyl iodide in DMF. The reaction produced pure PEMEDA-β-CD after precipitation of the compound

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• corannulene (1) to afford predominantly the cyclopropanated product 9 [39], whereas methyllithium adds to 10, giving the 1,2-addition product 11, after alkylation of the resulting anion by methyl iodide [40]. In contrast to these examples, no planar PAH has ever been observed to suffer direct covalent bond

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

• Tao Wang,
• Patrick Rabe,
• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311

• diazonium salt followed by a Sandmeyer reaction resulted in 4b (61% over two steps). The isomer 4c was efficiently prepared by double methylation of 2-chlororesorcinol (8) with potassium carbonate and methyl iodide in acetone (88%), while 4f was obtained by chlorination of dimethoxybenzene 9 with

• mixture of mono- and disubstitution products, but the target compounds 10f and 10g were obtained in better yields (29% and 17%). Derivative 10b was prepared from 3,5-dichlorocatechol (13) by methylation with potassium carbonate and methyl iodide in high yield (80%). Accordingly, methylation of 4,6

Synthesis of axially chiral gold complexes and their applications in asymmetric catalyses

• Yin-wei Sun,
• Qin Xu and
• Min Shi

Beilstein J. Org. Chem. 2013, 9, 2224–2232, doi:10.3762/bjoc.9.261

• quantitative yield upon treating the benzimidazole ring of (S)-12 with methyl iodide in acetonitrile under reflux (Scheme 2). Moreover, treatment of the benzimidazole ring of (S)-12 by using benzyl bromide upon heating in dioxane could produce the corresponding benzimidazolium salt (S)-14 also in quantitative

Non-cross-linked polystyrene-supported 2-imidazolidinone chiral auxiliary: synthesis and application in asymmetric alkylation reactions

• Quynh Pham Bao Nguyen and
• Taek Hyeon Kim

Beilstein J. Org. Chem. 2013, 9, 2113–2119, doi:10.3762/bjoc.9.248

• investigated. As shown in Table 3, benzyl bromide, allyl iodide and methyl iodide reacted very well to give the alkylated products 7 in moderate to good yields and excellent de values of >99% (Supporting Information File 1). Especially, the diastereocontrol of asymmetric methylation in this case was better