Pathway-Dependent Post-assembly Modification of an Anthracene-Edged MII4L6 Tetrahedron

FeII4L6 tetrahedral cage 1 undergoes post-assembly modification (PAM) via a Diels–Alder cycloaddition of the anthracene panels of the cage with tetracyanoethylene (TCNE). The modified cage 2 possesses an enclosed cavity suitable for encapsulation of the fullerene C60, whereas original cage 1 forms a unique covalent adduct through a Diels–Alder cycloaddition of three of its anthracene ligands with C60. This adduct undergoes further PAM via reaction of the remaining three ligands with TCNE, enabling the isolation of two distinct products depending on the order of addition of C60 and TCNE. Modified cage 2 was also able to bind an anionic guest, [Co(C2B9H11)2]−, which was not encapsulated by the original cage, demonstrating the potential of PAM for tuning the binding properties of supramolecular hosts

Covalent Post-assembly Modification Triggers Multiple Structural Transformations of a Tetrazine-Edged Fe4L6 Tetrahedron

Covalent post-assembly modification (PAM) reactions are useful synthetic tools for functionalizing and stabilizing self-assembled metal-organic complexes. Recently, PAM reactions have also been explored as stimuli for triggering supramolecular structural transformations. Herein we demonstrate the use of inverse electron-demand Diels-Alder (IEDDA) PAM reactions to induce supramolecular structural transformations starting from a tetrazine-edged FeII4L6 tetrahedral precursor. Following PAM, this tetrahedron rearranged to form three different architectures depending on the addition of other stimuli: an electron-rich aniline or a templating anion. By tracing the stimulus-response relationships within the system, we deciphered a network of transformations that mapped different combinations of stimuli onto specific transformation products. Given the many functions being developed for self-assembled three-dimensional architectures, this newly established ability to control the interconversion between structures using combinations of different stimulus types may serve as the basis for switching the functions expressed within a system.D.A.R. acknowledges the Gates Cambridge Trust. B.S.P. acknowledges the Royal Commission for the Exhibition of 1851 Fellowship and Corpus Christi College, Cambridge. This work was supported by the UK Engineering and Physical Sciences Research Council (EP/M01083X/1)

Post-assembly Modification of Tetrazine-Edged Fe(II)4L6 Tetrahedra.

Post-assembly modification (PAM) is a powerful tool for the modular functionalization of self-assembled structures. We report a new family of tetrazine-edged Fe(II)4L6 tetrahedral cages, prepared using different aniline subcomponents, which undergo rapid and efficient PAM by inverse electron-demand Diels-Alder (IEDDA) reactions. Remarkably, the electron-donating or -withdrawing ability of the para-substituent on the aniline moiety influences the IEDDA reactivity of the tetrazine ring 11 bonds away. This effect manifests as a linear free energy relationship, quantified using the Hammett equation, between σ(para) and the rate of the IEDDA reaction. The rate of PAM can thus be adjusted by varying the aniline subcomponent.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC). The au-thors thank Diamond Light Source (UK) for synchro-tron beamtime on I19 (MT8464), the Department of Chemistry NMR facility, University of Cambridge, and the EPSRC UK National Mass Spectrometry Facility at Swansea University. D.A.R. acknowledges the Gates Cambridge Trust for Ph.D. funding. B.S.P. acknowledges the Herchel Smith Research Fellowship from the University of Cambridge and the Fellowship from Corpus Christi College, Cambridge.This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b0508

The chemistry of phosphines in constrained, well-defined microenvironments

Developments in the confinement of phosphines within micro- or nano-environments are explored. Phosphines are ubiquitous across metal coordination chemistry and underpin some of the most famous homogeneous transition metal catalysts. Constraining phosphines within confined environments influences not only their behaviour but also that of their metal complexes. Notable examples include the use of metal–organic frameworks (MOFs) or metal–organic cages (MOCs) to support phosphines which demonstrate how the microenvironment within such constructs leads to reactivity modification. The development of phosphine confinement is explored and parallels are drawn with related constrained macrocyclic systems and mechanically interlocked molecules. The review concludes by identifying areas that remain a challenge and those that will provide new avenues for research

Short and Efficient Syntheses of Protoberberine Alkaloids using Palladium-Catalyzed Enolate Arylation

A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladium‐catalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50 % is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine‐containing derivative synthesized here

Palladium-catalyzed enolate arylation as a key C-C bond-forming reaction for the synthesis of isoquinolines.

The palladium-catalyzed coupling of an enolate with an ortho-functionalized aryl halide (an α-arylation) furnishes a protected 1,5-dicarbonyl moiety that can be cyclized to an isoquinoline with a source of ammonia. This fully regioselective synthetic route tolerates a wide range of substituents, including those that give rise to the traditionally difficult to access electron-deficient isoquinoline skeletons. These two synthetic operations can be combined to give a three-component, one-pot isoquinoline synthesis. Alternatively, cyclization of the intermediates with hydroxylamine hydrochloride engenders direct access to isoquinoline N-oxides; and cyclization with methylamine, gives isoquinolinium salts. Significant diversity is available in the substituents at the C4 position in four-component, one-pot couplings, by either trapping the in situ intermediate after α-arylation with carbon or heteroatom-based electrophiles, or by performing an α,α-heterodiarylation to install aryl groups at this position. The α-arylation of nitrile and ester enolates gives access to 3-amino and 3-hydroxyisoquinolines and the α-arylation of tert-butyl cyanoacetate followed by electrophile trapping, decarboxylation and cyclization, C4-functionalized 3-aminoisoquinolines. An oxime directing group can be used to direct a C-H functionalization/bromination, which allows monofunctionalized rather than difunctionalized aryl precursors to be brought through this synthetic route

Mechanically interlocked molecular handcuffs

The field of mechanically interlocked molecules that employ a handcuff component are reviewed. The variety of rotaxane and catenane structures that use the handcuff motif to interlock different components are discussed and a new nomenclature, distilling diverse terminologies to a single approach, is proposed. By unifying the interpretation of this class of molecules we identify new opportunities for employing this structural unit for new architectures

Perfluorinated Ligands Induce Meridional Metal Stereochemistry to Generate M8L12, M10L15, and M12L18 Prisms.

Meridional (mer) coordination promotes the generation of larger and lower-symmetry prismatic metallosupramolecular structures, in contrast with the facial (fac) coordination common to smaller and higher-symmetry polyhedra. Here, we describe a general route to the selective formation of large metallosupramolecular prisms that contain exclusively mer-coordinated metal vertices. The use of 2-formylpyridine subcomponents that contain perfluorophenylene substituents at their 5-positions resulted in stereoselective formation of the iron(II) complexes from these subcomponents. Only mer vertices were observed, as opposed to the statistical fac/mer mixture otherwise generated. This mer-selective self-assembly could be used to prepare tetragonal (M8L12), pentagonal (M10L15), and hexagonal (M12L18) prisms by taking advantage of the subtle selectivities imposed by the different anilines and counterions employed. The equilibrium between the tetragonal and pentagonal prism followed a linear free-energy relationship, with the ratio between structures correlating with the Hammett σp(+) parameter of the incorporated aniline. The contrasting preferences of the fluorinated and nonfluorinated ligands to generate prisms and tetrahedra, respectively, were quantified energetically, with the destabilization increasing linearly for each "incorrect ligand" incorporated into either structure.This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642192 and was supported by the UK Engineering and Physical Sciences Research Council (EPSRC). The authors thank Diamond Light Source (UK) for synchrotron beamtime on I19 (MT8464 and MT11397), the Department of Chemistry NMR facility, University of Cambridge, and the EPSRC UK National Mass Spectrometry Facility at Swansea University. M.K. acknowledges the Cambridge Commonwealth, European and International Trust and the Frédéric Fontaine scholarship from Michelin SCA. B.S.P. acknowledges the Herchel Smith Research Fellowship from the University of Cambridge and a Fellowship from Corpus Christi College, Cambridge. D.A.R. acknowledges the Gates Cambridge Trust for Ph.D. funding.This is the final version of the article. It first appeared from the American Chemical Society via https://doi.org/10.1021/jacs.6b0244

MASC 2022: What challenges and opportunities do supramolecular chemists face in coming years?

Supramolecular chemistry has gone from strength to strength in recent decades, with its impact felt from catalysis to materials science to chemical biology. This Voices article, published to coincide with the 2022 Macrocyclic and Supramolecular Chemistry Group meeting at the University of Nottingham, UK, asks speakers from the meeting: what are the major challenges and opportunities facing the field in coming years

Signal transduction in a covalent post-assembly modification cascade

Natural reaction cascades control the movement of biomolecules between cellular compartments. Inspired by these systems, we report a synthetic reaction cascade employing post-assembly modification reactions to direct the partitioning of supramolecular complexes between phases. The system is composed of a self-assembled tetrazine-edged FeII8L12 cube and a maleimide-functionalized FeII4L6 tetrahedron. Norbornadiene (NBD) functions as the stimulus that triggers the cascade, beginning with the inverse-electron-demand Diels–Alder reaction of NBD with the tetrazine moieties of the cube. This reaction generates cyclopentadiene as a transient by-product, acting as a relay signal that subsequently undergoes a Diels–Alder reaction with the maleimide-functionalized tetrahedron. Cyclooctyne can selectively inhibit the cascade by outcompeting NBD as the initial trigger. Initiating the cascade with 2-octadecyl NBD leads to selective alkylation of the tetrahedron upon cascade completion. The increased lipophilicity of the C18-tagged tetrahedron drives this complex into a non-polar phase, allowing its isolation from the initially inseparable mixture of complexes