Benzylidene Acetal Research Articles

Cyclic Acetals as Expanding Monomers to Reduce Shrinkage.

Polarity-reversal catalysts (PRCs) for hydrogen-atom transfer reactions have been known in radical chemistry for more than 60 years but are rarely described and utilized in the field of photopolymerization up to now. Herein, we present the use of thiols in a unique dual function as thiol-ene click reagents and as polarity-reversal catalyst (PRC) for the radical-mediated redox rearrangements of benzylidene acetals. During the rearrangement reaction, cyclic benzylidene acetals are transformed into benzoate esters leading to a significant volumetric expansion to reduce thermoset shrinkage. We were able to show that this expansion on a molecular level reduces shrinkage and polymerization stress but does not significantly affect the (thermo-)mechanical properties of the cross-linked networks. One of the key advantages of this process lies in its simplicity. No additives like sensitizers or combinations of different initiators (radical and cationic) are needed. Furthermore, the same light source can be used for both the polymerization reaction and expansion through rearrangement. Additionally, the applied photoinitiator enables spatial and temporal control of the polymerization; thus, the developed system can be an excellent platform for additive manufacturing processes.

A mild deprotection of isopropylidene ketals from 2-deoxyglycosides using AcOH/H2O/DME: An efficient regioselective deprotection of terminal isopropylidene ketals

This paper describes a mild and efficient catalytic deprotection method for isopropylidene ketals and benzylidene acetals using AcOH/H2O/DME(1,2-Dimethoxyethane). The method effectively removes ketal and acetal protecting groups from 2-deoxyglycosides which are prone to hydrolysis under acidic conditions. Moreover, it enables the selective removal of the terminal ketal over an internal one.

Sulfonated Graphene as a Sustainable Catalyst for Environmentally Benign Preparation of Benzylidene Acetals of Carbohydrates

AbstractA clean and efficient method has been developed for the introduction of benzylidene acetals into carbohydrate derivatives catalyzed by sulfonated graphene at room temperature. Yields were excellent in each case. The catalyst can be reused several times without much decrease in reactivity.

Lewis Acid Promoted Deprotection of Benzylidene Acetals and p-Methoxybenzyl Ethers with Mercaptoacid Acid as Scavenger.

We demonstrate a new and high-yielding method for removal of benzylidene acetals and para-methoxybenzyl ethers under catalytic conditions (BF3:OEt2 orFeCl3, 10 mol%) with mercaptoacetic acid as a scavenger. The reaction coproducts are converted to water-soluble molecules, which can be removed by aqueous extraction, thereby bypassing the need for chromatographic purification. The reaction was demonstrated on both multimilligram and multigram scale.

P2O5-Al2O3 Catalyzed One Pot Acetylation, Benzylidene Acetal Protection and Benzylidene Removal of Sugar Derivatives

An environment-friendly, simple and efficient one-pot acetylation and benzylidene acetal formation procedure has been introduced for the synthesis of sugar derivatives using P2O5-Al2O3 as a solid acid catalyst under solvent-free condition at room temperature, with excellent overall yield. This benzylidene acetal has been deprotected using the same reagent but in a moist condition.

Regioselective Reductive Opening of Benzylidene Acetals with Dichlorophenylborane/Triethylsilane: Previously Unreported Side Reactions and How to Prevent Them.

Arylidene acetals are widely used protecting groups, because of not only the high regioselectivity of their introduction but also the possibility of performing further regioselective reductive opening in the presence of a hydride donor and an acid catalyst. In this context, the Et3SiH/PhBCl2 system presents several advantages: silanes are efficient, environmentally benign, and user-friendly hydride donors, while PhBCl2 opens the way to unique regioselectivity with regard to all other Brønsted or Lewis acids used with silanes. This system has been extensively used by several groups, and we have demonstrated its high regioselectivity in the reductive opening of 4,6- and 2,4-O-p-methoxybenzylidene moieties in protected disaccharides. Surprisingly, its use on 4,6-O-benzylidene-containing substrates 1 and 2 led to unreproducible yields due to the unexpected formation of several side products. Their characterizations allowed us to identify different pitfalls potentially affecting the outcome of reductive opening of arylidenes with the Et3SiH/PhBCl2 reagent system: alkene hydroboration, azide reduction, and/or Lewis acid-promoted cleavage of the arylidene. With this knowledge, we optimized reproducible and high-yielding reaction conditions that secure and extend the scope of the Et3SiH/PhBCl2 system as a reagent for the regioselective opening of arylidenes in complex and multifunctional molecules.

Retraction: Influence of 2-(diisopropylamino)ethyl methacrylate on acid-triggered hydrolysis of cyclic benzylidene acetals and their importance in efficient drug delivery

Retraction of ‘Influence of 2-(diisopropylamino)ethyl methacrylate on acid-triggered hydrolysis of cyclic benzylidene acetals and their importance in efficient drug delivery’ by Minjie Tang et al., Polym. Chem., 2015, 6, 6671–6679, https://doi.org/10.1039/C5PY00734H.

Divergent approach to the synthesis of (-)-balanol heterocycle and cis-3-hydroxypipecolic acid based on chiral 2-aminoalkanol equivalent

Enantioselective synthesis of the hexahydroazepine core of (−)-balanol and formal synthesis of cis -3-hydroxypipecolic acid from a common intermediate have been accomplished by a divergent path. The common intermediate was accessed from a favorably protected enantiomerically pure 2-amino-1,3,4-butanetriol (ABT) equivalent via oxidation and Wittig olefination. The synthesis of (−)-balanol heterocycle featured tandem reduction/acetal-deprotection/γ-lactonization reaction and a one-pot azide reduction followed by seven membered aza-heterocycle formation while the route to cis -3-hydroxypipecolic acid highlighted the base induced piperidine ring formation and regioselective benzylidine-acetal cleavage. • Synthesis of piperidine/hexahydroazepine core is accomplished. • Benzylidene acetal is used as prominent chiral C4 building block. • Involves the tandem reduction/acetal deprotection/ γ -lactonization reaction.

Ionic Liquid Catalyzed Per-O-Acetylation and Benzylidene Ring-Opening Reaction

Tunable aryl imidazolium ionic liquids acting as Brønsted acid ionic liquids were found to be efficient catalysts for per-O-acetylation and reductive ring opening of benzylidene acetals. This method requires a truly catalytic amount of the least expensive available ionic liquids that are water-stable and reusable and also stable at room temperature. The reactions were obtained in one hour with good to excellent yields. These reactions can form C−O and C−H bonds with a high atom economy. Furthermore, the ionic liquid is an anomeric selective catalyst in per-O-acetylation and reductive ring opening of benzylidene acetals of sugar moieties.

Command-destruct thermosets via photoinduced thiol-catalyzed β-scission of acyclic benzylidene acetals

Photoinduced thiol-catalyzed hydrogen abstraction and β-scission of acyclic benzylidene acetals is demonstrated as a new route to “command-destruct” polymer thermosets.

Trehalose-Rich, Degradable Hydrogels Designed for Trehalose Release under Physiologically Relevant Conditions

Trehalose, a natural disaccharide, is primarily known for its ability to protect proteins from inactivation and denaturation caused by a variety of stress conditions. Furthermore, over the past few years, it has emerged as a promising therapeutic candidate for treatment of neurodegenerative diseases. Herein, we examine the attachment of trehalose to polymers for release under selected physiologically relevant conditions. The proposed strategies are evaluated specifically using hydrogels undergoing simultaneous degradation during trehalose release. These materials are fabricated via copolymerization of the appropriate acrylamide-type monomers with polymerizable trehalose esters or benzylidene acetals. This provides trehalose release in a slightly alkaline (i.e., pH 7.4) or mildly acidic (i.e., pH 5.0) environment, respectively. Using this method materials containing up to 51.7 wt% of trehalose are obtained. The presented results provide a solid basis for future studies on polymeric materials intended for trehalose release in biological systems.

Triphenylcarbenium Tetrafluoroborate as an Efficient Catalyst in the Regioselective Reductive Ring Opening of Benzylidene Acetals of Carbohydrates

AbstractTriphenylcarbenium tetrafluoroborate was found to be an efficient catalyst for the highly regioselective reductive ring opening of 4,6‐benzylidene acetals of hexopyranosides using DIBAL−H as the reducing agents to furnish the primary 6‐OH alcohols in good to excellent yield.

Alkynylation of Pentose Derivatives with Stereochemical Fidelity: Implications for the Regioselectivity of Alkynyl Diol Cycloisomerizations to Cyclic Enol Ethers.

This work characterizes a previously undetected epimerization in the preparation of alkynyl diols from pentose precursors utilizing the Ohira-Bestmann reagent. Lithium trimethylsilyldiazomethane (Colvin reagent) additions to the d-ribose and d-lyxose-derived benzylidene acetals provide the respective alkynyl diol stereoisomers, without epimerization. Regioselective tungsten-catalyzed cycloisomerizations of the d-ribose- and d-lyxose-derived alkynyl diols yield rigid bicyclic pyranose glycals, confirming the stereochemical fidelity of the Colvin alkynylation process.

A Direct Method for the Efficient Synthesis of Benzylidene Acetal at Room Temperature

For the first time, a metal‐free direct method has been developed for the efficient synthesis of benzylidene acetal at room temperature using Dowex 50WX8 as a solid acid catalyst and Cl3CCN as a novel water scavenger. At room temperature, a wide variety of aryl and α,β‐unsaturated aldehydes react readily with functionalized 1,2‐ and 1,3‐diols to furnish the corresponding acetals in very good yields. Labile functional groups, like N‐Boc, N‐Cbz, ‐OTBDMS, ‐OBn, ‐N3 and acetonide are found to be stable under the reaction conditions. The versatility of this method is further demonstrated with carbohydrate substrates and optically active diols.

The use of the novel glycosyl acceptor and supramer analysis in the synthesis of sialyl-α(2–3)-galactose building block

A new glycosyl acceptor to be used in sialylation was designed as a 3-hydroxy derivative of 4-methoxyphenyl β-d-galactopyranoside with 2-O-acetyl group and O-4 and O-6 protected as benzylidene acetal. Two alternative syntheses of this compound were compared. Sialylation of 3-OH group of the glycosyl acceptor with O-chloroacetylated N-trifluoroacetylneuraminic acid phenyl thioglycoside (NIS, TfOH, MeCN, MS 3 Å, −40 °C) was studied in a wide concentration range (5–150 mmol L−1). The outcome of sialylation generally followed the predictions of supramer analysis of solutions of sialyl donor in MeCN, which was performed by polarimetry and static light scattering and revealed two concentration ranges differing in solution structure and the structures of supramers of glycosyl donor. The optimized conditions of sialylation (C = 50 mmol L−1) were used to synthesize protected Neu-α(2–3)-Gal disaccharide (78%, α:β = 13:1), which was then converted to sialyl-α(2–3)-galactose imidate building block useful for the synthesis of complex sialo-oligosaccharides.

Chapter 4: Formation and Cleavage of Benzylidene Acetals Catalyzed by NaHSO4·SiO2 by Lifeng Sun, Xin-Shan Ye, and Xingdi Wang

Chapter 4: Formation and Cleavage of Benzylidene Acetals Catalyzed by NaHSO4·SiO2 by Lifeng Sun, Xin-Shan Ye, and Xingdi Wang

Concise synthesis of 2,7-anhydrosialic acid derivatives and its application

In N-acetylneuraminic acid, apart from O9 and O8, a possible glycosylation site is the O4 position. For example, gangliosides HLG-2 and HPG-7 are considered to be potential lead compounds for carbohydrate-based drug development to treat neural disorders. However, the construction of their α(1 → 4) fucosyl sialic acid and α(2 → 4) linkages between sialic acids is difficult because of the regioselectivity problem. Herein, N-acetyl-2,7-anhydroneuraminic acid was synthesized in three steps from Neu5Ac methyl ester through per-O-trimethylsilylation, heating-assisted intramolecular anomeric protection (iMAP) and desilylation. The iMAP simultaneously circumvents both the 2- and 7-OH protection. Upon protecting the 8- and 9-OH groups as a benzylidene acetal, only 4-OH is free for glycosylation. These 2,7-anhydro-8,9-O-benzylidenesialic acid derivatives were examined as acceptor for an α-selective fucosylation to construct the glycosidic linkage of fucosyl α(1 → 4) 2,7-anhydroneuraminic acid.

Substituent Effects on the pH Sensitivity of Acetals and Ketals and Their Correlation with Encapsulation Stability in Polymeric Nanogels.

The effect of structural variations in acetal- and ketal-based linkers upon their degradation kinetics is studied through the design, synthesis, and study of six series of molecules, comprising a total of 18 different molecules. Through this systematic study, we show that the structural fine-tuning of the linkers allows access to variations in kinetics of degradation of more than 6 orders of magnitude. Hammett correlations show that the ρ value for the hydrolysis of benzylidene acetals is about -4.06, which is comparable to an SN1-like process. This shows that there is a strong, developing positive charge at the benzylic position in the transition state during the degradation of acetals. This positively charged transition state is consistent with the relative degradation rates of acetals vs ketals (correlated to stabilities of 1°, 2°, and 3° carboxonium ion type intermediates) and the observed effect of proximal electron-withdrawing groups upon the degradation rates. Following this, we studied whether the degradation kinetics study correlates with pH-sensitive variations in the host-guest characteristics of polymeric nanogels that contains these acetal or ketal moieties as cross-linking functionalities. Indeed, the trends observed in the small molecule degradation have clear correlations with the encapsulation stability of guest molecules within these polymeric nanogels. The implications of this fundamental study extend to a broad range of applications, well beyond the polymeric nanogel examples studied here.

Synthesis of racemic Entecavir

Racemic Entecavir was prepared from Corey lactone diol benzylidene acetal in four steps in 24% overall yield.

A catalytic enantioselective approach to tetrol bearing vicinal all-carbon quaternary stereogenic centers.

The first highly enantioselective catalytic protocol for selective manipulation of tetrol benzylidene acetals through chiral phosphoric acid mediated oxidative desymmetrization is reported. This efficient approach provides a general access to vicinal all-carbon quaternary stereogenic center structural motifs, as well as structures containing vicinal tertiary and quaternary stereocenters enantioselectively. The synthetic utility has been furthermore demonstrated by transformations and gram-scale processes.