Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• productivity of AGA. Results and Discussion We selected three glycan sequences as models to analyze the effect of different parameters on the AGA outcome. Each sequence was prepared on four batches of Merrifield resin functionalized with two photolabile linkers (L1 [22] vs L2 [3]), at two linker loadings (low

Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions

• Edgar Peris,
• Raúl Porcar,
• María Macia,
• Jesús Alcázar,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159

• under continuous flow conditions. Results and Discussion Scheme 1 summarizes the synthetic approach used for the preparation of the functionalized polymers considered in this work. A commercially available PS-DVB bead-type macroporous chloromethylated polymer 1 (Merrifield resin with 20% DVB and 1.2

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• the efficiency of synthesising and purifying immobilised photosensitisers [63]. A BODIPY photosensitiser was immobilised to an aldehyde-functionalised Merrifield resin (poly(styrene-co-divinylbenzene-co-4-formylstyrene)) in continuous flow and concurrently in an analogous batch procedure. The coupling

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• required to access all six oligosaccharides, ranging from hexa- to dodecasaccharides. Results and Discussion The automated syntheses of oligomannosides 4–6 and oligoarabinomannosides 7–9 were performed on a self-built automated synthesizer using a Merrifield resin functionalized with a photocleavable

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• were equipped with two benzyl ethers to account for the low reactivity of glucuronic acids as glycosylating agents and carried either Fmoc or Lev groups. As solid support, we chose photolabile-linker-functionalized Merrifield resin 4 for its compatibility with the activation conditions for glycosyl

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

• methanediphenyl diisocyanate [76]. The authors demonstrated that compared with conventional heating, the reaction was faster (3–10 min) and with higher yields. Analogously, β-CD was grafted onto PEGylated Merrifield resin by reaction with HDI under MW irradiation [77]. CD nanosponges from anhydrous β-CD and

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• halophosphonium salts in Appel and dehydration reactions [44]. This work utilized a commercially available polymer-supported phosphine oxide based on the Merrifield resin architecture, and it is noteworthy that the reactions reported in this manuscript required a 6-fold excess of the halophosphonium salt compared

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

• responsible for the poor de value [17], and Merrifield resin was an unsuitable support [14]. In contrast, the asymmetric benzylation in the soluble polymer 5a gave excellent diastereoselectivity (>99% de) which was not affected by the base or reaction time (Table 2, entries 2–5). Interestingly, although

• having a similar functional structure to that of the Merrifield resin, soluble polymer 4a showed the potential to be a good support under our condition. With the optimized reaction conditions in hand, the asymmetric alkylation reactions using NCPS-supported 2-imidazolidinone chiral auxiliaries 5 were

• , entry 4). Conclusion In summary, an NCPS-supported 2-imidazolidinone chiral auxiliary was developed with the following three clear advantages: (1) high loading capacity (more than 1.0–1.5 mmol/g loading of Wang resin or Merrifield resin), (2) remarkable solubility properties that are extremely useful

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• , different solid supports have been developed (Figure 1, [27][28]). The most commonly used solid support for organic synthesis is the Merrifield resin [1]. This polystyrene (PS) resin shows good swelling properties in organic media but is not compatible with the aqueous conditions that are often required for

• functionalized with linker 1 (Scheme 4). Coupling to both chloro-functionalized Merrifield resin 16 and Jandajel 17 was achieved by a tetrabutylammonium iodide (TBAI) mediated substitution in the presence of Cs2CO3. Capping of unreacted chlorides by cesium acetate and subsequent acidic hydrolysis of the THP

• used. Unfortunately, an efficient cleavage of the products from Merrifield resin was impossible since PS resins fail to swell in water. When dioxane was used to swell the PS resin, some partially deprotected compounds were detected. Other polar solvents that suppress the described side reactions and

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• biomacromolecules at high concentrations of strong acids, a polystyrene resin was chosen that contains a tritylchloride linker. The resin was obtained by treatment of Merrifield resin with p-hydroxytriphenylmethyl alcohol and subsequent chlorination [49][50]. This tritylchloride linker allowed a mild cleavage of

• the acid labile products using less than 0.5% trifluoroacetic acid (TFA) in dichloromethane. The loading of the Merrifield resin occurred in pretty good yields as the ratio of the measured to the calculated loading value was 0.70 mmol/g to 0.78 mmol/g (Scheme 1). The synthesis started with the

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

• NIS/TfOH to Merrifield resin 11, as determined by HPLC (see Supporting Information File 1). Based on these unexpected findings, we hypothesized that excess glycosylating agent may alkylate the sulfamyl group during glycosylation, such that subsequent cleavage provides products 20 and 21. To test this

• Merrifield resin 12 containing only the safety-catch cleavage site (Scheme 4). The presence of glycosylated linker 23 as the main product confirmed that premature linker cleavage had occurred. Even nonglycosylated resin 12 was cleaved by treatment with sodium methoxide to afford linker 7 (Scheme 4). A

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• 10.3762/bjoc.8.132 Abstract The synthesis of diverse substituted indole structures on solid supports is described. The immobilization of nitrobenzoic acid onto Merrifield resin and the subsequent treatment with alkenyl Grignard reagents delivered indole carboxylates bound to solid supports. In contrast to

• limitations are presented. Keywords: chemical diversity; cross-coupling reactions; indole; Merrifield resin; Introduction Indoles are heterocyclic structures of unquestionable importance. It is well recognized that the indole moiety is a privileged structural motif found in numerous natural products, such

• chromatographic steps and the direct use of ortho,ortho-unsubstituted nitroarenes. Results and Discussion Synthetic plan Based on our initial findings, we attached a variety of nitrobenzoic acids onto solid supports. The resin of choice was Merrifield resin with an initial loading of 0.97 mmol/g. Hence, a number

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• transformation. Undeniably, polymer beads prepared without any Cinchona organocatalyst present did also catalyze the reaction. However, we found that several other polymer resins, such as unmodified Merrifield resin (chloromethylated and cross-linked polystyrene), influence the reaction in the same manner

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• Merrifield resin, and propargyloxyproline derivative 2, which was readily obtained in two steps from commercially available (2S,4R)-N-Boc-4-hydroxyproline (Scheme 2). Based on previous experience, we considered that variations in the degree of cross-linking of the support resins could have an important

• effect on their mechanical stability [66], this resulting in differences in their performance. In order to assess this issue, we prepared two different immobilized catalysts, starting in one case (1a) from commercially available Merrifield resin containing 1% of 1,4,-divinylbenzene (DVB) as a cross

• -linking agent and in the other case (1b) from a home-made Merrifield resin with 8% DVB (prepared by radical copolymerization of styrene, 4-chloromethylstyrene and DVB, under previously reported conditions [77][78][79]). It is well known that slightly cross-linked (1–2% DVB) polystyrene is microporous in

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• or 34) on Merrifield resin in the first step. Reaction of the resin-bound sulfonyl intermediate 31 with hydrazine, followed by release from the resin and intramolecular cyclization, afforded 4-arylsulfonyl-3,5-diamino-1H-pyrazoles 32. Reaction of the resin-bound carbonyl intermediate 35 with

Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups

• Julien Rolland,
• Xacobe C. Cambeiro,
• Carles Rodríguez-Escrich and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2009, 5, No. 56, doi:10.3762/bjoc.5.56

• stereospecific ring-opening with piperazine, and the resulting diamino alcohol 3 is subsequently supported onto a slightly cross-linked (1% DVB) Merrifield resin by direct treatment at room temperature in DMF in the presence of cesium carbonate (Scheme 3). Evaluation of resin 2 under batch conditions Prior to

From discovery to production: Scale- out of continuous flow meso reactors

• Peter Styring and
• Ana I. R. Parracho

Beilstein J. Org. Chem. 2009, 5, No. 29, doi:10.3762/bjoc.5.29

• was packed with nickel immobilised onto Merrifield resin (mean average particles size of 45 μm when dry and 72 μm when wet in THF), with approximately 3% nickel loading. A syringe pump (RAZAL A-99) was used to pump a pre-determined volume of the solution of known concentrations at different flow rates

• temperature, using a nickel catalyst supported on Merrifield resin beads in a Swagelok meso reactor column, which is of the same dimensions as a single channel in a scaled-out parallel capillary reactor. The objective of this research was to demonstrate that it is possible practically to scale-out a reaction

• isolate individual channels to inspect their contents due to the large number of capillaries present. However, in order to ensure that the packing procedure was consistent we ran tests on a reactor packed with Merrifield resin beads without catalyst attached by pumping a solution of guaiazulene dye in THF

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• flow process for the addition of diethylzinc to various aldehydes was described recently (Scheme 4) [27]. Reagent solutions were fed by piston-pump driven flow through a fritted column packed with chiral amino-alcohol functionalized Merrifield resin 9. Under optimal conditions (10 °C, a flow rate of

• conversion of benzaldehyde to the desired (R)-alcohol 30 with 85:15 selectivity and 99% ee (Scheme 9). Lower enantioselectivities were observed in batch reactions using a homogeneous analogue (87% ee) and also for a heterogeneous analogue with the catalyst grafted onto Merrifield resin (89% ee). The monolith