Catalytic Asymmetric Mannich‐Type Reaction Enabled by Efficient Dienolization of α,β‐Unsaturated Pyrazoleamides†

(E)‐α,β‐Unsaturated pyrazoleamides undergo facile dienolization to furnish copper(I)‐(1Z,3Z)‐dienolates as the major in the presence of a copper(I)‐(R)‐DTBM‐SEGPHOS catalyst and Et₃N, which react with aldimines to afford syn‐vinylogous products as the major diastereoisomers in high regio‐ and enantioselectivities. In some cases, the diastereoselectivity is low, possibly due to the low ratio of copper(I)‐(1Z,3Z)‐dienolates to copper(I)‐(1Z,3E)‐dienolates. (Z)‐Allylcopper(I) species is proposed as effective intermediates, which may form an equilibrium with copper(I)‐(1Z,3Z)‐dienolates. Interestingly, the present methodology is a nice complement to our previous report, in which (E)‐β,γ‐unsaturated pyrazoleamides were employed as the prenucleophiles in the copper(I)‐catalyzed asymmetric vinylogous Mannich‐Type reaction and anti‐vinylogous products were obtained. In the previous reaction, copper(I)‐ (1Z,3E)‐dienolates were generated through α‐deprotonation, which might form an equilibrium with (E)‐allylcopper(I) species. Therefore, it is realized in the presence of a copper(I) catalyst that (E)‐α,β‐unsaturated pyrazoleamides lead to syn‐products and (E)‐β,γ‐unsaturated pyrazoleamides lead to anti‐products. Finally, by use of (E)‐β,γ‐unsaturated pyrazoleamide, (E)‐α,β‐unsaturated pyrazoleamide, (R)‐DTBM‐SEGPHOS, and (S)‐DTBM‐SEGPHOS, the stereodivergent synthesis of all four stereoisomers is successfully carried out. Then by following a three‐step reaction sequence, all four stereoisomers of N‐Boc‐2‐Ph‐3‐Me‐piperidine are synthesized in good yields, which potentially serve as common structure units in pharmaceutically active compounds.     

Implications of Nitrogen Doping on Geometrical and Electronic Structure of the Fullerene Dimers

Because of its unsaturated bonds, C₆₀ is susceptible to polymerize into dimers. The implications of nitrogen doping on the geometrical and electronic structure of C₆₀ dimers have been ambiguous for years. A quarter‐century after the discovery of azafullerene dimer (C₅₉N)₂, we reported its single crystallographic structure in 2019. Herein, the unambiguous crystal structure information of (C₅₉N)₂ is elucidated specifically, revealing that the inter‐cage C—C single bond length of (C₅₉N)₂ is comparable with that of an ordinary C(sp³)‐C(sp³) single bond, and that the most stable conformer of (C₅₉N)₂ is gauche‐conformer with a dihedral angle of 66°. To amend the structural deviations, geometrical structure of (C₅₉N)₂ is optimized by a B3LYP‐D3BJ function, which is proved to be more consistent with its single crystal structure than those by the commonly used B3LYP function. Moreover, the calculation method is also suitable for other representative fullerene dimers, such as (C₆₀)₂ and its divalent anion. Additionally, the dissociation of (C₅₉N)₂ at 473 K under mass spectrometric conditions suggests the inter‐cage C—C bond is relatively weaker than an ordinary C—C single bond, which can be explained by the interaction energies of inter‐cages.     

LHRH/TAT dual peptides-conjugated polymeric vesicles for PTT enhanced chemotherapy to overcome hepatocellular carcinoma

Combination therapy such as photothermal therapy (PTT) enhanced chemotherapy is regarded as a promising strategy for cancer treatment. Herein, we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL. To avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance, the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics: doxorubicin (DOX) and paclitaxel (PTX). Besides, indocyanine green (ICG) was encapsulated, and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric vesicles. The results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content, trigger drug release in responsive to the reductive environment, realize high cellular uptake via dual peptides and laser irradiation, and achieve higher cytotoxicity via chemo-photothermal combination therapy. Hence, the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.     

Contradictory effect of gold nanoparticle-decorated molybdenum sulfide nanocomposites on amyloid-β-40 aggregation

The effect of gold nanoparticle-decorated molybdenum sulfide (AuNP-MoS₂) nanocomposites on amyloid-β-40 (Aβ₄₀) aggregation was investigated. The interesting discovery was that the effect of AuNP-MoS₂ nanocomposites on Aβ₄₀ aggregation was contradictory. Low concentration of AuNP-MoS₂ nanocomposites could enhance the nucleus formation of Aβ₄₀ peptides and accelerate Aβ₄₀ fibrils aggregation. However, although high concentration of AuNP-MoS₂ nanocomposites could enhance the nucleus formation of Aβ₄₀ peptides, it eventually inhibited Aβ₄₀ aggregation process. It might be attributed to the interaction between AuNP-MoS₂ nanocomposites and Aβ₄₀ peptides. For low concentration of AuNP-MoS₂ nanocomposites, it was acted as nuclei, resulting in the acceleration of the nucleation process. However, the structural flexibility of Aβ₄₀ peptides was limited as the concentration of AuNP-MoS₂ nanocomposites was increased, resulting in the inhibition of Aβ₄₀ aggregation. These findings suggested that AuNP-MoS₂ nanocomposites might have a great potential to design new multifunctional material for future treatment of amyloid-related diseases.     

Recent advances in the applications of [1.1.1]propellane in organic synthesis

As a highly strained small molecule, [1.1.1]propellane has been widely used in various synthetic transformations owing to the exceptional reactivity of the central bond between the two bridgehead carbons. Utilizing strain-release approaches, the rapid development of strategies for the construction of bicyclo[1.1.1]pentane (BCP) and cyclobutane derivatives using [1.1.1]propellane as the starting material has been witnessed in the past few years. In this review, we highlight the most recent advances in this field. Accordingly, the reactivity of [1.1.1]propellane can be divided into three pathways, including radical, anionic and transition metal-catalyzed pathways under appropriate conditions.     

Visible light induced tandem reactions: An efficient one pot strategy for constructing quinazolinones using in-situ formed aldehydes under photocatalyst-free and room-temperature conditions

A facile tandem route has been developed for constructing quinazolinones from various aminobenzamides and in-situ generated aldehydes. Visible light was found to play a dual role: first oxidizes the alcohol to the aldehyde and then facilitates its cyclization with o-substituted aniline. Furthermore, alcohols are perfect alternatives to aldehydes because they are greener, more available, more economical, more stable, and less toxic than aldehydes. The first reaction step continuously provides material for the second step, which effectively reduces loss through volatilization, oxidation, and polymerization of the aldehyde, while avoiding its toxicity. A variety of quinazolinones can be prepared in the presence of visible light without any additional photocatalyst. The developed synthesis protocol proceeds with the merits of mild conditions, broad substrate scope, operational simplicity, and high atom efficiency, with an eco-energy source under metal-free, photocatalyst-free, and ambient conditions.     

A co-activation strategy for enhancing the performance of hematite in photoelectrochemical water oxidation

Hematite(α-Fe_2O_3) is a promising photoanode for photoelectrochemical(PEC) water splitting.However,the severe charge recombination and sluggish water oxidation kinetics extremely limit its use in photohydrogen conversion.Herein,a co-activation strategy is proposed,namely through phosphorus(P)doping and the loading of CoAl-layered double hydroxides(CoAl-LDHs) cocatalysts.Unexpectedly,the integrated system,CoAl-LDHs/P-Fe_2O_3 photoanode,exhibits an outstanding photocurrent density of 1.56 mA/cm~2 at 1.23 V(vs.reversible hydrogen electrode,RHE),under AM 1.5 G,which is 2.6 times of pureα-Fe_2O_3.Systematic studies reveal that the remarkable PEC performance is attributed to accelerated surface OER kinetics and enhanced carrier separation efficiency.This work provides a feasible strategy to enhance the PEC performance of hematite photoanodes.     

Dinitrile compound containing ethylene oxide moiety with enhanced solubility of lithium salts as electrolyte solvent for high-voltage lithium-ion batteries

A dinitrile compound containing ethylene oxide moiety (4,7-dioxa-1,10-decanedinitrile, NEON) is synthesized as an electrolyte solvent for high-voltage lithium-ion batteries. The introduction of ethylene oxide moiety into the conventional aprotic aliphatic dinitrile compounds improves the solubility of lithium hexafluorophosphate (LiPF₆) used commercially in the lithium-ion battery industry. The electrochemical performances of the NEON-based electrolyte (0.8 M LiPF₆?+?0.2 M lithium oxalyldifluoroborate in NEON:EC:DEC, v:v:v?=?1:1:1) are evaluated in graphite/Li, LiCoO₂/Li, and LiCoO₂/graphite cells. Half-cell tests show that the electrolyte exhibits significantly improved compatibility with graphite by the addition of vinylene carbonate and lithium oxalyldifluoroborate and excellent cycling stability with a capacity retention of 97 % after 50 cycles at a cutoff voltage of 4.4 V in LiCoO₂/Li cell. A comparative experiment in LiCoO₂/graphite full cells shows that the electrolyte (NEON:EC:DEC, v:v:v?=?1:1:1) exhibits improved cycling stability at 4.4 V compared with the electrolyte without NEON (EC:DEC, v:v?=?1:1), demonstrating that NEON has a great potential as an electrolyte solvent for the high-voltage application in lithium-ion batteries.