Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• activated by TMSOTf were conducted, and followed by Zemplén cleavage. Similarly, three equivalents of thioglycosides 17 and 19 were added three times (triple coupling) for each glycosylation employing DMTST or NIS/TfOH as an activator. In both instances, surprisingly, only N-glycoside 20 (minor product) and

Imidazolinium and amidinium salts as Lewis acid organocatalysts

• Oksana Sereda,
• Nicole Clemens,
• Tatjana Heckel and
• René Wilhelm

Beilstein J. Org. Chem. 2012, 8, 1798–1803, doi:10.3762/bjoc.8.205

• TMSOTf gave the product in 55% yield. In both cases the endo product was the major product. The reaction was followed by TLC and the temperature was gradually increased from –10 to 45 °C over 4 days in ca. 10 °C steps. Next, imidazolinium salt 7 [25] was used in the reaction. The formation of the product

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• was the glycosylation of compound 14 with building block 4 (Scheme 2), which proceeded efficiently in the presence of trimethylsilyl triflate (TMSOTf) as promoter at −10 °C to afford trisaccharide 15 with a yield of 80%. It is worth mentioning that glycosylation of an analogue of glucose 14 equipped

• glycosylation with building block 4 (2 × 5 equiv) for 1 h at −10 °C with TMSOTf used for activation. Radical reduction using tributyltinhydride and azobisisobutyronitrile (AIBN) was performed to convert the trichloroacetamide into an N-acetyl moiety, followed by methoxide-mediated cleavage to provide compound

• three steps for 4 (for a detailed description of the synthesis of compound 4 see the supporting information of [5]); 62% over three steps for 5. Reagents and conditions. (i) TMSOTf, DCM, −10 °C, 80%; (ii) NaOMe, MeOH; then KOH, MeOH, 60 °C; then Pd/C, H2, AcOH, MeOH, THF, H2O, rt, 76% over three steps

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• intermediates 26–28 is described in Scheme 2. First, acceptors 23–25 were prepared in good yields through the selective removal of the chloroacetate (thiourea) in disaccharides 20–22. Fucosylation of acceptor 23 with ethylthioglycoside 12 was first attempted under NIS and TMSOTf activation at low temperature

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• reagents and anhydrous solvents were used without further purification unless stated otherwise. TMSOTf was from Acros, Geele, Belgium, all other chemicals were from either Sigma-Fluka, Taufkirchen, Germany, Fisher Scientific, Schwerte, Germany or Merck Schuchardt, Darmstadt, Germany. Thin-layer

• ]. For 3,4-bis{[(2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl)oxy]methyl}furan (6) TMSOTf (100 µL) was added to a solution of furan 1 (1.28 g, 10 mmol) and imidate 2 (18.5 g, 25.0 mmol) in dry CH2Cl2 (150 mL) at −40 °C. The reaction was stirred for 2 h at 0 °C and then extracted with aq. NaHCO3 (100 mL

• C1´), 124.83 (C3, C4), 148.07 (C2, C5). Synthesis of (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF, 5): 3-Hydroxymethyl-4-{[(2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl-1-yl)-oxy]methyl}furan (3) was synthesized by adding TMSOTf (100 µL) to an ice cooled solution of

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• oxygen, similarly to that known for O-pentenyl glycosides [30]. It is possible that the activation of the AP leaving group can also be achieved with TMSOTf or BF3·Et2O via the direct anomeric activation pathway, which was expected to become the key feature of the AP-mediated glycosylation approach in

• range of standard glycosyl acceptors 2–5 [18]. Encouragingly, the reaction of glycosyl donor 1a with the primary glycosyl acceptor 2 in the presence of TMSOTf was completed within 15 min and provided the corresponding disaccharide 6a in 82% yield (Table 1, entry 1). As expected, when a control

• experiment was set up with MeOTf, no glycosylation of 2 took place (Table 1, entry 2). The fact that the AP group in 1a can be activated with TMSOTf, but not with MeOTf, offers a basis for exploring its orthogonality to thioglycosides. This is because thioglycosides show a completely opposite reactivity

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• –d, to give the corresponding 2-[3-(alkylcarbamoyl)propionyl] tethered saccharides 5a–d. Intramolecular, ring closing glycosylation of the saccharides with NIS and TMSOTf afforded the tethered β(1→3) linked disaccharides 6a–c, the α(1→3) linked disaccharides 7a–d and the α(1→2) linked disaccharide 8d

• the benzylidene group was observed under these conditions. Compound 3b has not been described in the literature so far. It was prepared by first glucosylating 4-(benzyloxycarbonylamino)butanol [34] with 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl trichloroacetimidate [35] (cat. TMSOTf, CH2Cl2, −10 °C

• were intramolecularly glycosylated by activating the phenylthio group with the NIS-TMSOTf reagent (Scheme 1) [37]. Attention had to be paid to the choice of solvent, because the tethered glycosides 5 were only poorly soluble in most solvents that are usually applied for glycosylations with

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• , we reported a new synthesis of pyridines based on the trimethylsilyl trifluoromethanesulfonate (TMSOTf) induced cyclocondensation reaction of β-ketoenamides [29][30][31][32][33][34]. This cyclocondensation step can be rationalized as a 6π-electrocyclization of the disilylated intermediate 5 to

• cyclocondensation must be induced or completed by treatment with TMSOTf and an amine base in a suitable solvents at elevated temperatures. In order to minimize the operational effort, the process can be performed as quasi-one-pot procedure without purification of the intermediary β-ketoenamide. Scope and

• due to alternative hydrogen bond formation with the NH unit to the pyridine nitrogen rather than to the carbonyl group. Subsequent cyclocondensation with TMSOTf and NEt3 in 1,2-dichloroethane gave the expected pyridine derivatives, which were directly converted into pyrid-4-yl nonaflates in a second

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• 84 was prepared by a previously described procedure [23]. Next 5-bromovinyluracil (BVUr) was silylated and reacted with 84 in the presence of TMSOTf as the Lewis acid. This was followed by deacetylation with anhydrous K2CO3 in MeOH to provide the di-O-benzylated nucleoside 85 in 73% yield. For the

• analogues 124f–i afforded 5-[alkoxy(4-nitrophenyl)methyl]uridines 126f–i and 127f–i (Scheme 22) [35]. In a first step, the alkoxy uracils 124 were silylated and then reacted with a protected ribose in the presence of TMSOTf to afford diastereomeric mixtures of nucleosides 125. Diasteroisomers were separated

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• %). Orthoesters are common by-products of glycosylation reactions and typically rearrange under acidic conditions to give trans-linked glycosides [43]. Thus, 14 and 16 were treated with 0.25 equiv of an alternative Lewis acid, TMSOTf, and allowed to react for a longer time to allow the intermediate orthoester to

• isomerize. Under these conditions the disaccharide 26 was isolated in an improved yield of 63%. Also isolated was a 6-O-trimethylsilyl ether (6%), resulting from the reaction of alcohol 14 with TMSOTf. Better still, treatment of 14 and 16 with 0.25 equiv of BF3·Et2O afforded 26 in 76% yield. A similar

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans – an approach to carbohydrate mimetics

• Fabian Pfrengle and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 75, doi:10.3762/bjoc.6.75

• , even after prolonged reaction times. The reactions with stoichiometric amounts of TMSOTf gave monocyclic, bicyclic, and spirocyclic dihydropyrans depending on the 1,3-dioxolanyl-substituted enol ether employed (Table 2). Unfortunately, attempts to generate an eight-membered (or six-membered) ring by

• -type cyclization. Thus, 2-lithiofuran was added to nitrone 2a [18] and then protected with TBSOTf to give hydroxylamine derivative syn-4f in 55% (Scheme 4). Remarkably, subsequent treatment with 2 equiv of TMSOTf did not lead to the desired bicyclic product. Since no conversion was observed, the lower

• respective 1,3-dioxolanyl-substituted enol ether (1 equiv) in CH2Cl2 (6 mL/mmol) at −30 °C, was added TMSOTf (2 equiv) and the resulting solution stirred until it slowly reached room temperature (6 h). The reaction was quenched by the addition of water. After separation of the layers, the aqueous phase was

Benzyne arylation of oxathiane glycosyl donors

• Martin A. Fascione and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2010, 6, No. 19, doi:10.3762/bjoc.6.19

• turn the α-directing participating group into an anomeric leaving group reactive enough to partake in glycosylations. Thioglycosides are widely used as glycosyl donors [14][15], and many different reagents are available for their activaton including N-iodosuccinimide (NIS)/TMSOTf [16], dimethyl

Acid- mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

• Katsunori Tanaka and
• Koichi Fukase

Beilstein J. Org. Chem. 2009, 5, No. 40, doi:10.3762/bjoc.5.40

• method [27]. For the present microfluidic sialylation, a propionitrile solution of sialyl donor 1a and acceptor 2 with various concentrations was mixed with TMSOTf solution in dichloromethane at −78 °C using an IMM micromixer [42] with a channel width of 40 μm at a flow rate of 1.0 mL/min (Table 1

• , acceptor 2, and TMSOTf were adjusted to 0.15 M, 0.1 M, and 0.08 M, respectively, disaccharide 3a was obtained in only 14% yield and a large amount of the acceptor 2 was recovered (entry 1). However, we were pleased to find that the yield of 3a dramatically increased (88%) when the concentration of the

• severe problem under such drastic conditions [41]. The use of excess amounts of donor 1a and/or TMSOTf in batch reaction did not improve the sialylation yield, but rather resulted in a large amount of glycal production. Apparently, the efficient micromixing between substrates and the high concentration

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

Tether- directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes

• Peter J. Jervis and
• Liam R. Cox

Beilstein J. Org. Chem. 2007, 3, No. 6, doi:10.1186/1860-5397-3-6

• precursors in hand, we were ready to conduct our intramolecular allylation study. Each aldehyde substrate (>95:5 d.r. in all four cases) was treated with TMSOTf in the presence of 2,4,6-tri-t-butyl pyrimidine (TTBP), [24] which acts as a Brønsted acid scavenger, in CH2Cl2 as solvent, conditions that had

The oxanorbornene approach to 3-hydroxy, 3,4-dihydroxy and 3,4,5-trihydroxy derivatives of 2-aminocyclohexanecarboxylic acid

• Ishmael B. Masesane,
• Andrei S. Batsanov,
• Judith A. K. Howard,
• Raju Mondal and
• Patrick G. Steel

Beilstein J. Org. Chem. 2006, 2, No. 9, doi:10.1186/1860-5397-2-9

• or various trapping agents (e.g. TMSCl, TMSOTf) were partially successful, albeit only on very small scale, the use of a less coordinating potassium counterion (KHMDS) allowed the isolation of the dihydroanthranilate esters 4 and 5 in 71% and 69% yield respectively together with variable amounts of