Peptide cyclisation promoted by supramolecular complex formation

Phenol ester activated dipeptides that are reluctant to ring-closure have been cyclised with the aid of sterically shielding metallo-porphyrins avoiding unwanted intermolecular reactions. The binding of ZnTPP to the dipyridine-functionalised...

Chirality-matched catalyst-controlled macrocyclization reactions

Macrocycles, formally defined as compounds that contain a ring with 12 or more atoms, continue to attract great interest due to their important applications in physical, pharmacological, and environmental sciences. In syntheses of macrocyclic compounds, promoting intramolecular over intermolecular reactions in the ring-closing step is often a key challenge. Furthermore, syntheses of macrocycles with stereogenic elements confer an additional challenge, while access to such macrocycles are of great interest. Herein, we report the remarkable effect peptide-based catalysts can have in promoting efficient macrocyclization reactions. We show that the chirality of the catalyst is essential for promoting favorable, matched transition-state relationships that favor macrocyclization of substrates with preexisting stereogenic elements; curiously, the chirality of the catalyst is essential for successful reactions, even though no new static (i.e., not “dynamic”) stereogenic elements are created. Control experiments involving either achiral variants of the catalyst or the enantiomeric form of the catalyst fail to deliver the macrocycles in significant quantity in head-to-head comparisons. The generality of the phenomenon, demonstrated here with a number of substrates, stimulates analogies to enzymatic catalysts that produce naturally occurring macrocycles, presumably through related, catalyst-defined peripheral interactions with their acyclic substrates.

Recent Progress in Metal-Catalyzed [2+2+2] Cycloaddition Reactions

Metal-catalyzed [2+2+2] cycloaddition is a powerful tool that allows rapid construction of functionalized 6-membered carbo- and heterocycles in a single step through an atom-economical process with high functional group tolerance. The reaction is usually regio- and chemoselective although selectivity issues can still be challenging for intermolecular reactions involving the cross-[2+2+2] cycloaddition of two or three different alkynes and various strategies have been developed to attain high selectivities. Furthermore, enantioselective [2+2+2] cycloaddition is an efficient means to create central, axial, and planar chirality and a variety of chiral organometallic complexes can be used for asymmetric transition-metal-catalyzed inter- and intramolecular reactions. This review summarizes the recent advances in the field of [2+2+2] cycloaddition.1 Introduction2 Formation of Carbocycles2.1 Intermolecular Reactions2.1.1 Cyclotrimerization of Alkynes2.1.2 [2+2+2] Cycloaddition of Two Different Alkynes2.1.3 [2+2+2] Cycloaddition of Alkynes/Alkenes with Alkenes/Enamides2.2 Partially Intramolecular [2+2+2] Cycloaddition Reactions2.2.1 Rhodium-Catalyzed [2+2+2] Cycloaddition2.2.2 Molybdenum-Catalyzed [2+2+2] Cycloaddition2.2.3 Cobalt-Catalyzed [2+2+2] Cycloaddition2.2.4 Ruthenium-Catalyzed [2+2+2] Cycloaddition2.2.5 Other Metal-Catalyzed [2+2+2] Cycloaddition2.3 Totally Intramolecular [2+2+2] Cycloaddition Reactions3 Formation of Heterocycles3.1 Cycloaddition of Alkynes with Nitriles3.2 Cycloaddition of 1,6-Diynes with Cyanamides3.3 Cycloaddition of 1,6-Diynes with Selenocyanates3.4 Cycloaddition of Imines with Allenes or Alkenes3.5 Cycloaddition of (Thio)Cyanates and Isocyanates3.6 Cycloaddition of 1,3,5-Triazines with Allenes3.7 Cycloaddition of Aldehydes with Enynes or Allenes/Alkenes3.8 Totally Intramolecular [2+2+2] Cycloaddition Reactions4 Conclusion

Constructing covalent organic nanoarchitectures molecule by molecule via scanning probe manipulation

Constructing low-dimensional covalent assemblies with tailored size and connectivity is challenging yet often key for applications in molecular electronics where optical and electronic properties of the quantum materials are highly structure dependent. We present a versatile approach for building such structures block by block on bilayer sodium chloride (NaCl) films on Cu(111) with the tip of an atomic force microscope, while tracking the structural changes with single-bond resolution. Covalent homo-dimers in cis and trans configurations and homo-/hetero-trimers were selectively synthesized by a sequence of dehalogenation, translational manipulation and intermolecular coupling of halogenated precursors. Further demonstrations of structural build-up include complex bonding motifs, like carbon–iodine–carbon bonds and fused carbon pentagons. This work paves the way for synthesizing elusive covalent nanoarchitectures, studying structural modifications and revealing pathways of intermolecular reactions.

Acyl(imidoyl)ketenes: Reactive Bidentate Oxa/Aza-Dienes for Organic Synthesis

Polyfunctional building blocks are essential for the implementation of diversity-oriented synthetic strategies, highly demanded in small molecule libraries’ design for modern drug discovery. Acyl(imidoyl)ketenes are highly reactive organic compounds, bearing both oxa- and aza-diene moieties, conjugated symmetrically to the ketene fragment, enabling synthesis of various skeletally diverse heterocycles on their basis. The highlights of reactions utilizing acyl(imidoyl)ketenes are high yields, short reaction time (about several minutes), high selectivity, atom economy, and simple purification procedures, which benefits the drug discovery. The present review focuses on the approaches to thermal generation of acyl(imidoyl)ketenes, patterns of their immediate transformations via intra- and intermolecular reactions, including the reactions of cyclodimerization, in which either symmetric or dissymmetric heterocycles can be formed. Recent advances in investigations on mechanisms, identifications of intermediates, and chemo- and regioselectivity of reactions with participation of acyl(imidoyl)ketenes are also covered.

Chirality-Matched Catalyst-Controlled Macrocyclization Reactions

<p>Macrocycles, formally defined as compounds that contain a ring with 12 or more atoms, continue</p><p>to attract great interest due to their important applications in physical, pharmacological and</p><p>environmental sciences. In syntheses of macrocyclic compounds, promoting intramolecular over</p><p>intermolecular reactions in the ring-closing step, is often a key challenge. Furthermore, syntheses</p><p>of macrocycles with stereogenic elements confer an additional challenge, while access to such</p><p>macrocycles are of great interest. Herein, we report the remarkable effect peptide-based catalysts</p><p>can have in promoting efficient macrocyclization reactions. We show that the chirality of the</p><p>catalyst is essential for promoting favorable, matched transition state relationships that favor</p><p>macrocyclization of substrates with pre-existing stereogenic elements; curiously, the chirality of</p><p>the catalyst is essential for successful reactions, even though no new stereogenic elements are</p><p>created. Control experiments involving either achiral variants of the catalyst, or the enantiomeric</p><p>form of the catalyst, fail to deliver the macrocycles in significant quantity in head-to-head</p><p>comparisons. The generality of the phenomenon, demonstrated here with a number of substrates,</p><p>stimulates analogies to enzymatic catalysts that produce naturally occurring macrocycles,</p><p>presumably through related, catalyst-defined outer-sphere interactions with their acyclic substrates.</p>

Chirality-Matched Catalyst-Controlled Macrocyclization Reactions

<p>Macrocycles, formally defined as compounds that contain a ring with 12 or more atoms, continue</p><p>to attract great interest due to their important applications in physical, pharmacological and</p><p>environmental sciences. In syntheses of macrocyclic compounds, promoting intramolecular over</p><p>intermolecular reactions in the ring-closing step, is often a key challenge. Furthermore, syntheses</p><p>of macrocycles with stereogenic elements confer an additional challenge, while access to such</p><p>macrocycles are of great interest. Herein, we report the remarkable effect peptide-based catalysts</p><p>can have in promoting efficient macrocyclization reactions. We show that the chirality of the</p><p>catalyst is essential for promoting favorable, matched transition state relationships that favor</p><p>macrocyclization of substrates with pre-existing stereogenic elements; curiously, the chirality of</p><p>the catalyst is essential for successful reactions, even though no new stereogenic elements are</p><p>created. Control experiments involving either achiral variants of the catalyst, or the enantiomeric</p><p>form of the catalyst, fail to deliver the macrocycles in significant quantity in head-to-head</p><p>comparisons. The generality of the phenomenon, demonstrated here with a number of substrates,</p><p>stimulates analogies to enzymatic catalysts that produce naturally occurring macrocycles,</p><p>presumably through related, catalyst-defined outer-sphere interactions with their acyclic substrates.</p>

Control of Dynamic sp3-C Stereochemistry

Stereogenic sp3-hybridized carbon centres are fundamental building blocks of chiral molecules. Unlike dynamic stereogenic motifs, such as sp3-nitrogen centres or atropisomeric biaryls, sp3-carbon centres are usually fixed, requiring intermolecular reactions to undergo configurational change. Here, we report the internal enantiomerization of fluxional carbon cages and the consequences of their adaptive configurations for the transmission of stereochemical information. The sp3-carbon stereochemistry of the rigid tricyclic cages is inverted through strain-assisted Cope rearrangements, emulating the low-barrier configurational dynamics typical for sp3 nitrogen inversion or conformational isomerism. This dynamic enantiomerization can be stopped, restarted, or slowed by external reagents, while the configuration of the cage is controlled by neighbouring, fixed stereogenic centres. As part of a phosphoramidite–olefin ligand, the fluxional cage acts as a conduit to transmit stereochemical information from the ligand while also transferring its dynamic properties to chiral-at-metal coordination environments, influencing catalysis and ligand exchange energetics.

Correlation Between Yield and Reduced Mass of Raw Materials in Enzymatic Reactions

Correlation between the yield in the enzymatic reaction and the molecular weight of the substrate as an approximation of the reduced mass of the raw materials was clarified. The correlation was expressed by the same regression equation as in general organic chemical reactions. The coefficient of the regression equation to distinguish between intramolecular and intermolecular reactions were better when the values for intramolecular reactions were used in the plot of literature yields versus predicted yields. It was also found that the adjustment of the reduced mass by the number of rotatable bonds was not necessary and was found to be a good representation of the characteristics of the enzymatic reaction.

Correlation Between Yield and Reduced Mass of Raw Materials in Enzymatic Reactions

Correlation between the yield in the enzymatic reaction and the molecular weight of the substrate as an approximation of the reduced mass of the raw materials was clarified. The correlation was expressed by the same regression equation as in general organic chemical reactions. The coefficient of the regression equation to distinguish between intramolecular and intermolecular reactions were better when the values for intramolecular reactions were used in the plot of literature yields versus predicted yields. It was also found that the adjustment of the reduced mass by the number of rotatable bonds was not necessary and was found to be a good representation of the characteristics of the enzymatic reaction.