Olefination of Aromatic Carbonyls via Site-Specific Activation of Cycloalkanone Ketals.

Skeletal editing is an important strategy in organic synthesis as it modifies the carbon backbone to tailor molecular structures with precision, enabling access to compounds with specific desired properties. Skeletal editing empowers chemists to transform synthetic approaches of target compounds across diverse applications from drug discovery to materials science. Herein, we introduce a new skeletal editing method to convert readily available aromatic carbonyl compounds into valuable unsaturated carboxylic acids with extended carbon chains. Our reaction setup enables a cascade reaction of enolization-[2+2]cycloaddition-[2+2]cycloreversion between aromatic carbonyl compounds and ketals of cyclic ketones to generate unsaturated carboxylic acids as ring-opening products. Through a simple design, our substrates are specifically activated to react at predetermined positions to enhance selectivity and efficiency. This practical method offers convenient access to versatile organic building blocks as well as provides fresh insights into manipulating traditional reaction pathways for new synthetic applications.

Progress in Catalytic Asymmetric Reactions with 7-Azaindoline as the Directing Group.

α-Substituted-7-azaindoline amides and α,ß-unsaturated 7-azaindoline amides have emerged as new versatile synthons for various metal-catalyzed and organic-catalyzed asymmetric reactions, which have attracted much attention from chemists. In this review, the progress of research on 7-azaindoline amides in the asymmetric aldol reaction, the Mannich reaction, the conjugate addition, the 1,3-dipole cycloaddition, the Michael/aldol cascade reaction, aminomethylation and the Michael addition-initiated ring-closure reaction is discussed. The α-substituted-7-azaindoline amides, as nucleophiles, are classified according to the type of α-substituted group, whereas the α,ß-unsaturated 7-azaindoline amides, as electrophiles, are classified according to the type of reaction.

Ir-Catalyzed Chemo-, Regio-, and Enantioselective Allylic Enolization of 6,6-Dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one Involving Keto-Enol Isomerization.

The utilization of 6,6-dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one made from an unsymmetrical 4,4-dimethylcyclohexane-1,3-dione in iridium-catalyzed allylic enolization involving keto-enol isomerization is accomplished under mild conditions. The chemoselectivity, regioselectivity, and enantioselectivity are facilitated by the quaternary carbon and adjusting the reaction conditions. This method provides the substituted 2-(but-3-en-2-yl)-3-hydroxy-6,6-dimethylcyclohex-2-en-1-ones in good to high yields with high level of chemo-, regio-, and enantioselectivities. The chiral carbon-fluorine bond formation is induced by an adjacent chiral carbon center of the allylated 3-hydroxy-6,6-dimethylcyclohex-2-en-1-one, as well.

Use of multikinase inhibitors/lenvatinib concomitant with locoregional therapies for the treatment of radioiodine-refractory differentiated thyroid cancer.

Locoregional recurrence of differentiated thyroid cancer (DTC) occurs in 20% of thyroid cancer patients. Currently, there are many strategies for management of locoregional recurrence of DTC that lead to local control of the disease. The introduction of lenvatinib into the therapeutic armamentarium provides a new option for the treatment of radioiodine-refractory DTC (RR-DTC). However, results for simultaneous treatment with lenvatinib and locoregional therapies are unknown in patients with RR-DTC. This paper reviews the current status of this approach and gives recommendations on the management of lenvatinib during concomitant locoregional procedures.

Possible Steps of the Carboxylation of Ribulose-1,5-biphosphate from Intermediates: 2,3-Enediol versus 1,2-Enol.

Ribulose 1,5-bisphosphate (RuBP) undergoes enolization to initiate fixation of atmospheric carbon dioxide in the plant carbon cycle. The known model assumes the binding of RuBP to the Rubisco active site with the subsequent formation of 2,3-enediol (2,3,4-trihydroxypent-2-ene-1,5-diyl diphosphate). In the present study, it is assumed that 1,2-enol (2,3,4-trihydroxypent-1-ene-1,5-diyl diphosphate) can be formed in the enolization step to initiate the carboxylation reaction. We have used Kohn-Sham density functional theory on WB97X-D3/Def2-TZVP levels to compare the reaction barriers in the two ways. We considered the pathways of carboxylation of 1/2-ene (mono/di)ol via the C1 and C2 carbons without taking into account the binding of RuBP to the magnesium ion. Calculations of Gibbs free energies confirm the equal probability of the formation of 2,3-enediol and 1,2-enol. Quantum-chemical modeling of enolization and carboxylation reactions supports the important role of the bridging water molecule and diphosphate groups, which provide proton transfer and lower reaction barriers. The results show that carbon dioxide fixation can occur without a magnesium ion, and binding with C1 can have a lower barrier (~12 kcal/mol) than with C2 (~23 kcal/mol).

Interstellar Enolization-Acetaldehyde (CH3 CHO) and Vinyl Alcohol (H2 CCH(OH)) as a Case Study.

Owing to the unique conditions in cold molecular clouds, enols-the thermodynamically less stable tautomers of aldehydes and ketones-do not undergo tautomerization to their more stable tautomers in the gas phase because they cannot overcome tautomerization barriers at the low temperatures. Laboratory studies of interstellar analog ices have demonstrated the formation of several keto-enol tautomer pairs in astrochemically relevant ice mixtures over the last years. However, so far only one of them, acetaldehyde-vinyl alcohol, has been detected in deep space. Due to their reactivity with electrophiles, enols can play a crucial role in our understanding of the molecular complexity in the interstellar medium and in comets and meteorites. To study the enolization of aldehydes in interstellar ices by interaction with galactic cosmic rays (GCRs), we irradiated acetaldehyde ices with energetic electrons as proxies of secondary electrons generated in the track of GCRs while penetrating interstellar ices. The results indicate that GCRs can induce enolization of acetaldehyde and that intra- as well as intermolecular processes are relevant. Therefore, enols should be ubiquitous in the interstellar medium and could be searched for using radio telescopes such as ALMA. Once enols are detected and abundances are established, they can serve as tracers for the non-equilibrium chemistry in interstellar ices thus eventually constraining fundamental reaction mechanisms deep inside interstellar ices.

Comparative Experimental and Theoretical Study of Mg, Al and Zn Aryloxy Complexes in Copolymerization of Cyclic Esters: The Role of the Metal Coordination in Formation of Random Copolymers.

Homogeneity of copolymers is a general problem of catalytic coordination polymerization. In ring-opening polymerization of cyclic esters, the rational design of the catalyst is generally applied to solve this problem by the equalization of the reactivities of comonomers-however, it often leads to a reduction of catalytic activity. In the present paper, we studied the catalytic behavior of BnOH-activated complexes (ВНТ)Mg(THF)2nBu (1), (ВНТ)2AlMe (2) and [(ВНТ)ZnEt]2 (3), based on 2,6-di-tert-butyl-4-methylphenol (BHT-H) in homo- and copolymerization of L-lactide (lLA) and ε-caprolactone (εCL). Even at 1:5 lLA/εCL ratio Mg complex 1 catalyzed homopolymerization of lLA without involving εCL to the formation of the polymer backbone. On the contrary, Zn complex 3 efficiently catalyzed random lLA/εCL copolymerization; the presence of mono-lactate subunits in the copolymer chain clearly pointed to the transesterification mechanism of copolymer formation. Both epimerization and transesterification side processes were analyzed using the density functional theory (DFT) modeling that confirmed the qualitative difference in catalytic behavior of 1 and 3: Mg and Zn complexes demonstrated different types of preferable coordination on the PLA chain (k2 and k3, respectively) with the result that complex 3 catalyzed controlled εCL ROP/PLA transesterification, providing the formation of lLA/εCL copolymers that contain mono-lactate fragments separated by short oligo(εCL) chains. The best results in the synthesis of random lLA/εCL copolymers were obtained during experiments on transesterification of commercially available PLLA, the applicability of 3/BnOH catalyst in the synthesis of random copolymers of εCL with methyl glycolide, ethyl ethylene phosphonate and ethyl ethylene phosphate was also demonstrated.

Speeding up Viedma Deracemization through Water-catalyzed and Reactant Self-catalyzed Racemization.

Viedma deracemization is based on solution phase racemization, dissolution of racemic or scalemic conglomerates and crystal growth through autocatalytic cluster formation. With rate limiting racemization, its acceleration by appropriate catalysts may result in speeding up deracemization. A conglomerate-forming chiral compound may principally racemize directly, or via reverse of its formation reaction. For a hydrazine derivative, we investigated available racemization pathways in presence of pyrrolidine or thiourea amine as base catalysts: via Mannich or aza-Michael reaction steps and their reverse, or by enolization. Racemization by enolization was computationally found to dominate, both under water-free conditions and in presence of water, involving a multitude of different pathways. Faster racemization in presence of water resulted indeed in more rapid deracemization, when the base was pyrrolidine. Under water-free conditions, the role of water as enolization catalyst is assumed by chiral hydrazine itself - in autocatalytic racemization and in which both reactant and product are catalysts.

Racemization of the Succinimide Intermediate Formed in Proteins and Peptides: A Computational Study of the Mechanism Catalyzed by Dihydrogen Phosphate Ion.

In proteins and peptides, d-aspartic acid (d-Asp) and d-ß-Asp residues can be spontaneously formed via racemization of the succinimide intermediate formed from l-Asp and l-asparagine (l-Asn) residues. These biologically uncommon amino acid residues are known to have relevance to aging and pathologies. Although nonenzymatic, the succinimide racemization will not occur without a catalyst at room or biological temperature. In the present study, we computationally investigated the mechanism of succinimide racemization catalyzed by dihydrogen phosphate ion, H2PO4-, by B3LYP/6-31+G(d,p) density functional theory calculations, using a model compound in which an aminosuccinyl (Asu) residue is capped with acetyl (Ace) and NCH3 (Nme) groups on the N- and C-termini, respectively (Ace-Asu-Nme). It was shown that an H2PO4- ion can catalyze the enolization of the Hα-Cα-C=O portion of the Asu residue by acting as a proton-transfer mediator. The resulting complex between the enol form and H2PO4- corresponds to a very flat intermediate region on the potential energy surface lying between the initial reactant complex and its mirror-image geometry. The calculated activation barrier (18.8 kcal·mol-1 after corrections for the zero-point energy and the Gibbs energy of hydration) for the enolization was consistent with the experimental activation energies of Asp racemization.

A Perylene Diimide Crystal with High Capacity and Stable Cyclability for Na-Ion Batteries.

Organic Na-host materials have are now actively pursued as an attractive alternative to conventional transition-metal compounds for development of sustainable sodium ion batteries; however, most of the organic compounds reported so far suffer from their low reversible capacity and poor cyclability. Here, we report a simple perylene diimide, 3,4,9,10-perylene-bis(dicarboximide) (PTCDI), which demonstrates remarkable electrochemical performances as an organic cathode for Na-ion batteries. With the high density of redox-active carbonyl groups in a stable π-conjugated structure, the PTCDI molecule can undergo a two-electron redox reaction with reversible insertion/extraction of 2 Na(+) ions per molecular unit, demonstrating a high capacity of 140 mAh g(-1), a strong rate performance with a reversible capacity of 103 mAh g(-1) at 600 mA g(-1) (5 C,1 C = 120 mA g(-1)) and a long-term cyclability with 90% capacity retention over 300 cycles. Because this PTCDI material is commercially available and nontoxic, it may serve as a new alternative cathode for Na-ion battery applications.

Synergistic Catalysis: Metal/Proton-Catalyzed Cyclization of Alkynones Toward Bicyclo[3.n.1]alkanones.

A highly efficient and practical synergistically metal/proton-catalyzed Conia-ene reaction for the synthesis of bicyclo[3.n.1]alkanones has been developed. This synergistic catalysis was successfully utilized in modifying natural compounds such as methyl dihydrojasmonate, α,ß-thujone, and 5α-cholestan-3-one. Furthermore, the bridged carbonyl group of bicyclo[3.2.1]alkanones could be easily attacked by nucleophiles to give the ring-opened cycloheptenone products or bicyclo[4.2.1]amide in excellent yields. These reactions provide rapid access to a diverse range of cyclic structures from simple starting materials or naturally occurring compounds.

Mechanistic insights on the iodine(III)-mediated α-oxidation of ketones.

The synthesis of α-substituted carbonyl compounds is of great importance due to their ubiquity in both natural and man-made biologically active compounds. The field of hypervalent iodine chemistry has been a great contributor to access these molecules. For example, the α-oxidation of carbonyl compounds has been one of the most investigated iodine(III)-mediated stereoselective transformations. Yet, it is also the transformation that has met the most challenge in terms of achieving high stereoselectivities. The different mechanistic pathways of the iodine(III)-mediated α-tosyloxylation of ketones have been investigated. The calculations suggest an unprecedented iodine(III)-promoted enolization process. Indications that iodonium intermediates could serve as proficient Lewis acids are reported. This concept could have broad impact and foster new developments in the field of hypervalent iodine chemistry.

Effect of reaction pH on enolization and racemization reactions of glucose and fructose on heating with amino acid enantiomers and formation of melanoidins as result of the Maillard reaction.

This study investigates the effect of reaction pH on enolization and racemization reactions of glucose and fructose on heating with amino acid enantiomers, can influence the formation of melanoidins as result of the Maillard reaction. Remarkable enolization reaction of sugars was observed in the course of the Maillard reaction. Especially, the degree of sugar enolization was increased as the pH levels increased, which was higher in fructose than glucose systems. Otherwise, enolization of sugars on heating with amino acid was higher in glucose than fructose systems. Formation of isomer in Glc/d-Lys, Fru/d-Asn and Fru/d-Lys were increased upon increase of pH levels. The relative amounts of isomers in Glc/l-Asn and Glc/d-Asn were decreased upon increase of pH levels. Browning development was dependent on the pH levels, being more significant for model systems apart from heated glucose solution alone. Browning development of fructose systems was higher than glucose-amino acid systems. The l- and d-isomers both showed different absorption in the UV-vis spectra and that these occur at similar shape. Every peak has a stable absorbance appeared in the range between 260 and 320nm, characteristic of melanoidins.