In Situ Metal-Assisted Ligand Modification Induces Mn4 Cluster-to-Cluster Transformation: A Crystallography,Mass Spectrometry,and DFT Study

Dehydration of (S,S)-1,2-bis(1H-benzo[d]imidazol-2-yl)ethane-1,2-diol (H₄L) to (Z)-1,2-bis(1H-benzo[d]imidazol-2-yl)ethenol) (H₃L′) was found to be metal-assisted, occurs under solvothermal conditions (H₂O/CH₃OH), and leads to [Mn^II₄(H₃L)₄Cl₂]Cl₂ ⋅ 5 H₂O ⋅ 5 CH₃OH ( Mn₄L₄ ) and [Mn^II₄(H₂L′)₆(μ₃-OH)]Cl ⋅ 4 CH₃OH ⋅ H₂O ( Mn₄L′₆ ), respectively. Their structures were determined by single-crystal XRD. Extensive ESI-MS studies on solutions and solids of the reaction led to the proposal consisting of an initial stepwise assembly of Mn₄L₄ from the reactants via [MnL] and [Mn₂L₂] below 80 °C, and then disassembly to [MnL] and [MnL₂] followed by ligand modification before reassembly to Mn₄L′₆ via [MnL′], [MnL′₂], and [Mn₂L′₃] with increasing solvothermal temperature up to 140 °C. Identification of intermediates [Mn₄L_xL′_6−x] (x=5, 4, 3, 2, 1) in the process further suggested an assembly/disassembly/in situ reaction/reassembly transformation mechanism. These results not only reveal that multiple phase transformations are possible even though they were not realized in the crystalline state, but also help to better understand the complex transformation process between coordination clusters during “black-box” reactions.     

Copper Bis(oxazoline)-Catalyzed Enantioselective Alkynylation of Benzopyrylium Ions

The stereocontrolled construction of biologically relevant chromanones and tetrahydroxanthones has been achieved through the addition of alkynes to benzopyrylium trilfates under the influence of copper bis(oxazoline) catalysis. Excellent levels of enantiocontrol (63–98 % ee) are achieved in the addition of a variety of alkynes to an array of chromenones with a hydrogen in the 2-position. Promising levels of enantiocontrol (54–67 % ee) are achieved in the alkynylation of chromenones with esters in the 2-position, generating tertiary ether stereocenters resembling those frequently found in naturally occurring metabolites.     

Transition-Metal-Free Multiple Functionalization of Piperidines to 4-Substituted and 3,4-Disubstituted 2-Piperidinones

Remote and multiple functionalization of piperidines without the use of transition-metal catalysts and elaborate directing groups is one of the major challenges in organic synthesis. Herein is reported an unprecedented two-step protocol that enables the multiple functionalization of piperidines to either 4-substituted or trans-3,4-disubstituted 2-piperidones. First, by exploiting the duality of TEMPO reactivity, which under oxidative and thermal conditions fluctuates between cationic and persistent-radical form, a novel multiple C(sp³)-H oxidation of piperidines to α,β-unsaturated 2-piperidones was developed. Second, the intrinsic low reactivity of the unsaturated piperidones toward conjugated Grignard additions was overcome by using trimethylsilyl chloride (TMSCl) as Lewis acid. Subsequently, conjugated Grignard addition/electrophilic trapping protocol provided substituted 2-piperidone intermediates, some of which were then transformed into pharmaceutical alkaloids.     

Sulfuryl Fluoride Mediated Synthesis of Amides and Amidines from Ketoximes via Beckmann Rearrangement

A metal-free and redox-neutral method for Beckmann rearrangement employing inexpensive and readily available SO₂F₂ gas is described. The reported transformation proceeds at ambient temperature and is compatible with a wide range of sterically and electronically diverse aromatic, heteroaromatic, aliphatic and lignin-like oximes providing amides in good to excellent yields. The reaction proceeds through the formation of an imidoyl fluoride intermediate that can also be used for the synthesis of amidines.     

Increasing Complexity: A Practical Synthetic Approach to Three-Dimensional,Cyclic Sulfoximines and First Insights into Their in Vitro Properties

A short synthetic approach with broad scope to access five- to seven-membered cyclic sulfoximines in only two to three steps from readily available thiophenols is reported. Thus, simple building blocks were converted to complex molecular structures by a sequence of S-alkylation and one-pot sulfoximine formation, followed by intramolecular cyclization. Seventeen structurally diverse cyclic sulfoximines were prepared in high overall yields. In vitro evaluation of these underrepresented, three-dimensional, cyclic sulfoximines with respect to properties relevant to medicinal chemistry did not reveal any intrinsic flaw for application in drug discovery.     

Iron-Catalyzed Cleavage Reaction of Keto Acids with Aliphatic Aldehydes for the Synthesis of Ketones and Ketone Esters

The radical–radical coupling reaction is an important synthetic strategy. In this study, the iron-catalyzed radical–radical cross-coupling reaction based on the decarboxylation of keto acids and decarbonylation of aliphatic aldehydes to obtain valuable aryl ketones is reported for the first time. Remarkably, when tertiary aldehydes were used as carbonyl sources, ketone esters were selectively obtained instead of ketones. The gram-scale preparation of aryl ketone through this strategy was easily achieved by using only 3 mol % of the iron catalyst. As a proof-of-concept, the bioactive molecule flurprimidol was synthesized in two steps by using this strategy.     

The Forgotten Pyrazines: Exploring the Dakin–West Reaction

Pyrazines are an underreported class of N-heterocycles available from nitrogen-rich biomass presenting an interesting functional alternative for current aromatics. In this work, access to pyrazines obtained from amino acids by using the 90 year old Dakin–West reaction was explored. After a qualitative screening several functional proteinogenic amino acids proved good substrates for this reaction, which were successfully scaled to multigram scale synthesis of the corresponding intermediate α-acetamido ketones. Subsequently, the conditions towards pyrazine formation using δ-amino-levulinic acid were optimized, and these were employed to synthesize a relevant set of five functional dimethylpyrazines in high purity. These pyrazines can be considered a versatile toolbox of aromatic building blocks for a wide range of applications, such as in the synthesis of polymers or metal–organic frameworks.     

Trifluorosulfonylation Cascade in Allenols: Stereocontrolled Synthesis of Bis(triflyl)enones

Herein, we report investigations embodying the first example of reversal of the native regioselectivity in the reaction of allenols with electrophiles. The effortlessness of C−C bond formation, mild reaction conditions, neither catalysts nor light irradiation, and exquisite selectivity, both in terms of functional-group tolerance and chemo-, site-, and stereo-selectivity, converts this trifluorosulfonylation-rearrangement sequence into an appealing protocol for the preparation of novel functionalized enones. The synthetic utility of this method has been validated by the conversion of the initially prepared bis(triflyl)enones into a variety of bis(triflyl)-functionalized molecules such as 1,3-dienes, allylic alcohols, pyrroles, pyrazoles, and chromenes. Besides, DFT calculations have provided a reliable understanding of observed selectivity.     

Three-Component Reaction for the Synthesis of Highly Functionalized Propargyl Ethers

Multicomponent reactions provide efficient means to access molecular complexity. Herein, we report a copper-catalyzed three-component reaction of diazo compounds, alcohols and ethynyl benziodoxole (EBX) reagents for the synthesis of propargyl ethers. Extensive variations of the three partners of the reaction is possible, leading to highly functionalized and structurally diverse products under mild conditions. Alkynylation of a copper ylide intermediate is postulated as key step for this transformation.     

Recent Advances in Iodine-Promoted C−S/N−S Bonds Formation

Sulfur-containing scaffold, as a ubiquitous structural motif, has been frequently used in natural products, bioactive chemicals and pharmaceuticals, particularly C−S/N−S bonds are indispensable in many biological important compounds and pharmaceuticals. Development of mild and general methods for C−S/N−S bonds formation has great significance in modern research. Iodine and its derivatives have been recognized as inexpensive, environmentally benign and easy-handled catalysts or reagents to promote the construction of C−S/N−S bonds under mild reaction conditions, with good regioselectivities and broad substrate scope. Especially based on this, several new strategies, such as oxidation relay strategy, have been greatly developed and accelerated the advancement of this field. This review focuses on recent advances in iodine and its derivatives promoted hybridized C−S/N−S bonds formation. The features and mechanisms of corresponding reactions are summarized and the results of some cases are compared with those of previous reports. In addition, the future of this domain is discussed.