Chemoselective synthesis of xanthenes and tetraketones in a choline chloride-based deep eutectic solvent

A chemoselective synthesis of tetraketone and xanthene derivatives, by means of tandem Knoevenagel condensation and Michael addition in choline chloride-based deep eutectic solvents (DESs), is presented. The reaction of readily available aldehydes and active methylene compounds in malonic acid- and ZnCl₂-based DES gives various xanthenes derivatives with good to excellent yields under mild reaction conditions. On the other hand, tetraketones were synthesized in almost quantitative yields by simple condensation of an aldehyde and active methylene compounds in milder deep eutectic solvents of urea and SnCl₂. In addition, the reaction of other types of choline chloride-based DES leads to a mixture of tetraketone and xanthene.     

Polystyrene-supported TiCl4 as a novel,efficient and reusable polymeric Lewis acid catalyst for the chemoselective synthesis and deprotection of 1,1-diacetates under eco-friendly conditions

Copolymer beads of styrene and divinylbenzene (5–7%) were synthesized and combined with titanium tetrachloride in CS₂ to form a stable complex. The PS/TiCl₄ complex was used as a mild and efficient polymer-supported Lewis acid catalyst for the preparation of 1,1-diacetates from various types of aldehydes under heterogeneous conditions at room temperature. Deprotection of the resulting 1,1-diacetates has also been achieved using the same catalyst in methanol. This new protocol has the advantages of easy availability, stability, reusability of the eco-friendly catalyst, high to excellent yields, chemoselectivity, simple experimental and work-up procedure. Moreover, this polymeric catalyst could be recovered easily and reused several times without significant loss in activity.     

Silica supported Br?nsted acids as catalyst in organic transformations:A comprehensive review

Br?nsted acid catalysts have been used in a number of organic transformations. To overcome limi‐tations, such as toxicity, volatility, high price and hazardous nature of the conventional methods, the c...     

Dual side-reactions limit the utility of a key polymer therapeutic precursor

In contrast to literature reports, the activated polyacid poly(methacryloxysuccinimide) reacts with nucleophiles to give, initially, a high proportion of ring-opened residues. This copolymer then reacts intramolecularly to form a polymer with a high fraction of glutarimide residues. These side reactions occur to such an extent as to preclude the use of poly(methacryloxysuccinimide) as a precursor to polymethacrylamides.     

A Metal‐Free Synthesis of 2‐Alkyl(or Aryl) Thiomethyl‐2‐cyclohexenones from Cyclic Morita–Baylis–Hillman Bromides

Under mild conditions, an efficient and rapid S‐allylation of thiols with cyclic Morita–Baylis–Hillman (MBH) bromides without the need of a transition‐metal catalyst or an expensive additive is described herein. Treatment of the MBH bromides with various thiols or ethane‐1,2‐dithiol in the presence of Et₃N regioselectively affords the corresponding 2‐alkyl(or aryl) thiomethyl‐2‐cyclohexenones or the perhydro benzo[1,4]dithiepinone, respectively, in moderate to good yields (40 – 73%). The reaction is rapid and carried out in THF at room temperature.     

Guanidine Additive Enabled Intermolecular ortho-Phthalaldehyde-Amine-Thiol Three-Component Reactions for Modular Constructions

Recently, ortho-phthalaldehyde (OPA) is experiencing a renascence for the modification of proteins and peptides through OPA-amine two-component reactions for bioconjugation and intramolecular OPA-amine-thiol three-component reactions for cyclization. Historically, small thiol molecules were used in large excess to allow for the intermolecular OPA-amine-thiol reaction forming 1-thio-isoindole derivatives. In this study, we discovered that guanidine could serve as an effective additive to switch the intermolecular OPA-amine-thiol three-component reaction to a stoichiometric process and enable the modular construction of peptide-peptide, and peptide-drug conjugate structures. Thus, 12 model peptide-peptide conjugates have been synthesized from unprotected peptides featuring all proteinogenic residues. Besides, 6 peptide-drug conjugates have been prepared in one step, with excellent conversions and isolated yields. In addition, a conjugate product has been further functionalized by utilizing a premodified OPA derivative, demonstrating the versatility and flexibility of this reaction.     

A Chemoselective Polarity-Mismatched Photocatalytic C(sp3)−C(sp2) Cross-Coupling Enabled by Synergistic Boron Activation**

We report the development of a C(sp³)−C(sp²) coupling reaction using styrene boronic acids and redox-active esters under photoredox catalysis. The reaction proceeds through an unusual polarity-mismatched radical addition mechanism that is orthogonal to established processes. Synergistic activation of the radical precursor and organoboron are critical mechanistic events. Activation of an N-hydroxyphthalimide (NHPI) ester by coordination to boron enables electron transfer, with decomposition leading to a nucleofuge rebound, activating the organoboron to radical addition. The unique mechanism enables chemoselective coupling of styrene boronic acids in the presence of other alkene radical acceptors. The scope and limitations of the reaction, and a detailed mechanistic investigation are presented.     

Chemoselective Quinoline and Isoquinoline Reduction by Energy Transfer Catalysis Enabled Hydrogen Atom Transfer

(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation and Birch reduction are the two broadly utilized approaches for (hetero)arene reduction across academia and industry over the last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline and isoquinoline reduction protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom transfer (HAT). The design of this protocol bypasses the conventional metric of reduction reaction, that is, the reductive potential, and instead relies on the triplet energies of the chemical moieties and the kinetic barriers of energy and hydrogen atom transfer events. Many reducing labile functional groups, which were incompatible with previous (hetero)arene reduction reactions, are retained in this reaction. We anticipate that this protocol will trigger the further advancement of chemoselective arene reduction and enable the current arene-rich drug space to escape from flatland.     

Synthesis of Phthalocyaninato Silicium Monooxide by Intramolecular Dehydration of Dihydroxo (Phthalocyaninato) Silicium

2,9,16,23-tetra-tetradecanophthalocyaninato silicium monooxide was first synthesized by the reaction of dihydroxo (2,9,16,23-tetra-tetradecano phthalocyaninato) silicium with NaOCH₃ The conversion was more than 90% and the selectivity was 100%.     

Amino acid intercalated layered double hydroxide catalyzed chemoselective methylation of phenols and thiophenols with dimethyl carbonate

Sixteen different amino acids are intercalated into Mg–Al layered double hydroxides (LDHs) by the reconstruction method and are characterized by powder XRD and FT-IR. The intercalated amino acid–LDHs (AA-LDHs) are used as catalysts for chemoselective O-methylation of phenol and S-methylation of thiophenol with dimethyl carbonate (DMC) as a green methylating agent. The intercalation behavior of various amino acids is influenced by various structural features of amino acids, namely, carbon chain length, structure, and physicochemical properties. In particular, amino acids possessing a hydrophobic side-chain show higher catalytic activity. A suitable reaction mechanism is proposed. The catalyst can also be recycled.