High Ring Strain Research Articles

Acetylenic Carbon-Containing Stable Five-Membered Metallacycles

Due to the linear property around an acetylenic carbon, the introduction of such an atom to a small cycle would result in high ring strain. Currently, the smallest isolated rings are five-membered, including metallacycloalkynes and metallapentalynes. Both types contain at least one unusual small bond angle around the acetylenic carbon, thus exhibiting abnormal reactivities. This feature article gives a comprehensive overview on these two kind complexes. The synthesis and reactivities are extensively described, the source of stability is presented, and the future prospect is discussed. The article aims to provide a better development for the chemical diversity of five-membered metallacycloalkynes and metallapentalynes.

Controlled Cyclopolymerization of 1,5-Hexadiynes to Give Narrow Band Gap Conjugated Polyacetylenes Containing Highly Strained Cyclobutenes.

For decades, cyclopolymerization of α,ω-diyne derivatives has been an effective method to synthesize various soluble polyacetylenes containing five- to seven-membered rings in the backbone. However, cyclopolymerization to form four-membered carbocycles was considered impossible due to their exceptionally high ring strain (∼30 kcal/mol). Herein, we demonstrate the successful cyclopolymerization of rationally designed 1,5-hexadiyne derivatives to afford various polyacetylenes containing highly strained cyclobutenes in each repeat unit. After screening, Ru catalysts containing bulky diisopropylphenyl groups promoted challenging four-membered ring cyclization efficiently from various monomers, enabling the synthesis of high molecular weight (up to 40 kDa) polyacetylenes in a controlled manner. Furthermore, living polymerization allowed for block copolymer synthesis by combining with ring-opening metathesis polymerization as well as block copolymerization of two different 1,5-hexadiyne monomers to give a fully conjugated polyacetylene. These new polymers unexpectedly showed much narrower band gaps than conventional substituted polyacetylenes by >0.2 eV. Interestingly, computational studies showed much smaller bond length alternation in the conjugated backbone containing cyclobutenes, resulting in highly delocalized π electrons along the polymer chain and lower band gaps.

Effect of substitution on dissociation kinetics of C2H5X, (X = F, Cl, Br and I): A theoretical study

The decomposition of alkyl halide is controversial concerning C–X bond dissociation reaction and molecular (HX) elimination reaction. In order to identify the feasibility of dissociation reaction, electronic structure calculations were performed at DFT level of theory in conjunction with BMK, B3LYP, and MPW1PW91 functional, and 6-311G** basis set. In addition to this, we have carried out the detail theoretical kinetic analysis for the unimolecular dissociation of ethyl halide (C2H5X, X = F, Cl, Br and I), in the temperature range from 500 to 1700 K and pressure range from 10−9 to 103 kPa. Our kinetic data for decomposition reaction reveals that, the order of reaction is independent on temperature, but it alters with applied pressure. Also, an analysis of the branching ratio of C–X bond dissociation and HX elimination reaction, as a function of temperature, shows that the molecular (HX) is eliminated predominantly from fluoro-, chloro- and bromo-derivative of ethane. On the other hand, the reverse trend was observed upon pyrolysis of iodoethane. Above discrepancy in dissociation behaviour has been attributed towards larger C–X bond length and higher ring strain in cyclic transition state structures involving heavier atom.

Synthetic Applications of Cyclopropene and Cyclopropenone: Recent Progress and Developments

AbstractSmallest ring size, high ring strain, and more reactivity of cyclopropene have brought the attention of researchers for chemical exploration. In this context, the chemistry of cyclopropene and cyclopropenone has exponentially grown over the last few years. This present review focuses on the most recent developments in cyclopropane chemistry.

Benzazetidines and Related Compounds: Synthesis and Potential.

Benzazetidines are a class of N-heterocycles potentially very interesting for a variety of purposes, including biological applications and drug design. In the past, their high ring strain has hampered the development of trustable, general, and efficient synthetic methodologies for their preparation. In this review article, the aim is to disclose all the literature contributions about the synthesis of these compounds and the study of their reactivity, from the early examples to the most recent synthetic approaches. Recently, there has been a growth of interest for this heterocycle, driven by the publication of novel synthetic methodologies based on palladium-catalyzed intramolecular C-H amination and organocatalyzed ring-closure of 2-(N-Boc-anilino)-α-ketoesters/amides.

Organocatalytic Synthesis of Benzazetidines by Trapping Hemiaminals with Protecting Groups.

Benzazetidines are highly strained and inherently unstable heterocycles. There are only few methodologies for assembling these compounds. Here, a protocol is presented to trap an elusive cyclic, four-membered hemiaminal structure. This method affords several benzazetidines in moderate to good yields (up to 81%), and it uses inexpensive materials and does not require catalysts based on transition metals. The high ring strain energy of these benzazetidine systems was estimated by density functional theory calculations to be about 32 kcal mol-1. This synthesis can be applied also on gram scale with reaction yield essentially unchanged.

4-Hydroxyproline-Derived Sustainable Polythioesters: Controlled Ring-Opening Polymerization, Complete Recyclability, and Facile Functionalization.

The sustainable production of chemically recyclable polymers presents a significant opportunity to polymer scientists to tackle the growing environmental and energy problems of current petroleum-based plastics. Despite recent advances, however, there are still pressing needs for an expanded horizon of chemically recyclable polymers. Herein, we introduce a new paradigm of biosourced polythioesters (PTEs) with high polymerizability and complete recyclability under mild and economical conditions. The thiolactone monomers with a high ring strain can be easily prepared in a two-step process from 4-hydroxyproline. Controlled ring-opening polymerizations (ROP) using inexpensive and weak bases afford PTEs with high molar masses ( Mn) up to 259 kg mol-1 and narrow dispersities generally below 1.15. The properties of PTEs can be readily adjusted by copolymerization and/or pre/post-functionalization on the side chains. Selective and complete depolymerizations of the PTEs in dilute solution at ambient to modest temperatures recycle clean monomers. Density functional theory (DFT) calculation of model reactions provides mechanistic insights and highlights the importance of judicious molecular design. Taken together, the unique ROP/depolymerization chemistry of such PTEs may offer a sustainable solution for creating and manufacturing high-value materials such as optical/photochemical plastics, self-immolative polymers, and degradable biomaterials under situations where recycle and reuse are indispensable.

Strain-Release-Driven Homologation of Boronic Esters: Application to the Modular Synthesis of Azetidines.

Azetidines are important motifs in medicinal chemistry, but there are a limited number of methods for their synthesis. Herein, we present a new method for their modular construction by exploiting the high ring strain associated with azabicyclo[1.1.0]butane. Generation of azabicyclo[1.1.0]butyl lithium followed by its trapping with a boronic ester gives an intermediate boronate complex which, upon N-protonation with acetic acid, undergoes 1,2-migration with cleavage of the central C-N bond to relieve ring strain. The methodology is applicable to primary, secondary, tertiary, aryl, and alkenyl boronic esters and occurs with complete stereospecificity. The homologated azetidinyl boronic esters can be further functionalized through reaction of the N-H azetidine, and through transformation of the boronic ester. The methodology was applied to a short, stereoselective synthesis of the azetidine-containing pharmaceutical, cobimetinib.

9-Membered Carbocycles: Strategies and Tactics for their Synthesis.

Many natural products comprising a nine‐membered carbocyclic core structure exhibit interesting biological effects. However, only a minority have succumbed to their synthesis in the past. The synthesis of functionalized nine‐membered carbocycles still remains a challenging goal for synthetic chemists, mainly due to their high ring strain. Different strategies to overcome the unfavorable enthalpic and entropic factors associated with their formation are highlighted in this Concept article. The presented methods are classified into two different categories: (1) the ring‐expansion of smaller rings or the ring‐contraction of larger rings and (2) the direct cyclization of acyclic precursors.

Electron-donating groups and high ring strain promoted ring opening of methylenecyclopropanes catalyzed by rhodium and iridium complexes

The possible ring-opening pathways of X-substituted MCPs (X = NO2, CF3, F, H, Ph, CH3, OH, NH2) promoted by MH(CO)(PY3)3 (M = Rh, Ir, Y = H, Ph) and Wilkinson's catalyst-[RhCl(PY3)3] (Y = H, Ph) were studied by density functional theory. The ring-opening reaction was initiated by the orbital interaction between the transition metal of catalyst and reactant MCP. The strong coordination ability of Ir with CC double bond and the inertness of complex intermediate caused the difficulty in further reaction steps of catalyst dissociation and hydride transfer, rationalizing that IrH(CO)(PPh3)3 catalyzed ring-opening reaction occurred at higher temperature (50 °C) than the RhH(CO)(PPh3)3 catalyzed one (room temperature). Without the medium hydride in RhCl(PPh3)3 catalyst, the CC bond of MCP cannot insert into the RhH bond and the hydride cannot be borrowed from RhCl(PPh3)3 like RhH(CO)(PPh3)3 catalyst, hence making the RhCl(PPh3)3-catalyzed reaction much more difficult to occur. The ring-opening step is predicted to be the rate-determining step for MH(CO)(PPh3)3 catalyst, which is different from the Cp2LnH (Ln = La, Lu) catalyzed reactions. Multifaceted factors of substituents including ring strain, electron-donating ability, and the steric effect of the substituents were revealed for MH(CO)(PPh3)3 catalyzed reactions when M = Rh and Ir. The hydroxyl substituted MCP (X = OH) bears not only higher ring strain but also the stronger electron-donating ability, leading to the lowest activation energy among the studied systems. Understanding of the multifaceted factors of substituents is useful for regulating the ring-opening reaction of substituted MCP promoted by transition metal complexes.

Fluxional behaviour of tricyclo[2.2.1.02,6]heptaphosphide trisanion: a DFT investigation

AbstractThe structures of the tricyclo[2.2.1.02,6]heptaphosphide trisanion, tricyclo[2.2.1.02,6]heptaphosphane triradical and their carbocyclic analogues have been investigated theoretically at the density functional theory (DFT) (B3LYP/6-31 + G*) level. The existence of negative hyperconjugation in these molecules could be established by natural bond orbital analysis. The weakening of theσbonds combined with the possibility of the valence-shell expansion at the anionic charge carrying phosphorus atoms in the tricyclo[2.2.1.02,6]heptaphosphide trisanion induces a degenerate [2,2]sigmatropic rearrangement with a low energy barrier making all the phosphorus atoms equivalent, as detected by31P NMR experimentally. This energy barrier is enhanced in the presence of counterions. Its carbocyclic analogue trisanion fails to undergo a [2,2]sigmatropic rearrangement due to the inability of the anionic carbon centres to expand their valence shell. The tricyclo[2.2.1.02,6]heptaphosphane triradical and its carbocyclic analogue undergo a [2,2]sigmatropic rearrangement, as valence-shell expansion at the carbon atom is not required in this case. A lower activation energy barrier for the [2,2]sigmatropic rearrangement of the tricyclo[2.2.1.02,6]heptane triradical as compared to that for its phospha-analogue can be rationalised on the basis of the higher ring strain of cyclopropane than triphosphirane.

Breaking a bottleneck: Accurate extrapolation to "gold standard" CCSD(T) energies for large open shell organic radicals at reduced computational cost.

Open Shell organic radicals are principal species involved in many diverse areas such as combustion, photochemistry, and polymer chemistry. Computational studies of such species with an accurate method like coupled-cluster with single and double and perturbative triple (CCSD(T)) may be restricted to systems of modest size due to the steep computational scaling of the method. Herein, we assess the accuracy of extrapolated CCSD(T) energies determined using the connectivity-based hierarchy (CBH) method on medium to large sized radicals. In our method, an MP2 calculation on the target radical is coupled with CCSD(T) energies of fragments determined uniquely by our hierarchy to perform accurate extrapolations. A careful assessment is done with a robust CBH-rad49 test set comprising of 49 diverse cyclic and acyclic radicals with a variety of functional groups. We demonstrate that the extrapolation method with CBH-2 or CBH-3 is sufficient to obtain sub-kcal accuracy. ROMP2 and PMP2 calculations with both Pople-style and Dunning-style basis-sets resulted in mean absolute errors for CCSD(T) extrapolation (full CCSD(T)-extrapolated CCSD(T)) within 0.5 kcal/mol. Further speedup for such CCSD(T) extrapolations are obtained with ROHF-based RI-MP2 calculations. Challenging systems with (a) high ring strain, (b) delocalized character, and (c) spin contamination are identified and analyzed in detail. Finally, we apply our extrapolation method on 10 larger radicals containing 10-15 heavy atoms, where accurate CCSD(T) energies are obtained at a fractional cost of full CCSD(T) calculations.

ChemInform Abstract: Intramolecular Cyclopropanation and C—H Insertion Reactions with Metal Carbenoids Generated from Cyclopropenes

AbstractReview: 81 refs.

Intramolecular cyclopropanation and C-H insertion reactions with metal carbenoids generated from cyclopropenes.

Activation of unsaturated carbon-carbon bonds by means of transition metal catalysts is an exceptionally active research field in organic synthesis. In this context, due to their high ring strain, cyclopropenes constitute an interesting class of substrates that displays a versatile reactivity in the presence of transition metal catalysts. Metal complexes of vinyl carbenes are involved as key intermediates in a wide variety of transition metal-catalyzed ring-opening reactions of cyclopropenes. Most of the reported transformations rely on intermolecular or intramolecular addition of nucleophiles to these latter reactive species. This Account focuses specifically on the reactivity of carbenoids resulting from the ring-opening of cyclopropenes in cyclopropanation and C-H insertion reactions, which are arguably two of the most representative transformations of metal complexes of carbenes. Compared with the more conventional α-diazo carbonyl compounds, the use of cyclopropenes as precursors of metal carbenoids in intramolecular cyclopropanation or C-H insertion reactions has been largely underexploited. One of the challenges is to devise appropriately substituted and readily available cyclopropenes that would not only undergo regioselective ring-opening under mild conditions but also trigger the subsequent desired transformations with a high level of chemoselectivity and stereoselectivity. These goals were met by considering several substrates derived from the readily available 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines. In the case of 1,6-cyclopropene-enes, highly efficient and diastereoselective gold(I)-catalyzed ring-opening/intramolecular cyclopropanations were developed as a route to diversely substituted heterocycles and carbocycles possessing a bicyclo[4.1.0]heptane framework. The use of rhodium(II) catalysts enabled us to widen the scope of this transformation for the synthesis of medium-sized heterocyclic scaffolds incorporating an eight-membered ring. The reactivity of rhodium(II) carbenoids generated from 3,3-dimethylcyclopropenylcarbinols was also investigated in intramolecular C(sp(3))-H insertions. Despite their low electrophilic character, these purely donor rhodium(II) carbenoids underwent remarkably efficient diastereoselective 1,5- or 1,6-C-H insertions allowing access to a wide variety of substituted cyclopentanols, cyclohexanols, bicycloalkanols, and tetrahydropyrans with high level of diastereoselectivity and with complete tolerance of a free hydroxyl group. The products arising from the gold(I)- or rhodium(II)-catalyzed ring-opening/intramolecular cyclopropanation or C-H insertion of 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines always incorporate an isopropylidene moiety, which can potentially undergo subsequent oxidative cleavage into a carbonyl group without epimerization. By virtue of this operation, the 3,3-dimethylcyclopropenyl group formally behaves as a valuable surrogate for an α-diazoketone, with obvious advantages considering the ease of access to the corresponding substrates and that no hazardous reagents are involved in their preparation. These studies have set a useful basis for the development of other reaction pathways involving metal carbenoids generated from these readily available families of substituted cyclopropenes, including the investigation of the yet underexploited synthetic potential of purely donor rhodium(II) carbenoids.

A facile and selective route to remarkably inert monocyclic NHC-stabilized boriranes.

Herein we report a facile and selective synthetic route to monocyclic NHC-stabilized boriranes. We have succeeded in obtaining two highly stable new boriranes through salt elimination of NHC-stabilized dichloroboranes with the dianion of trans-stilbene, Na2[C14H12]. One borirane was observed to undergo reaction with [Pt(PEt3)3], in which the Pt(0) center oxidatively adds a backbone C-H bond of the NHC, leading to the isolation of the Pt(II) complex trans-[(Et3P)2PtH{C=CH(NMe)2C·BPh(C14H12)}]. The remarkable inertness of the NHC-boriranes suggests a strong stabilising effect of quaternization of the boron atom.

Steric C-N bond activation on the dimeric macrocycle [{P(μ-NR)}2(μ-NR)]2.

Dimeric cyclophosphazanes [{P(μ-NR)}2(μ-NR)]2 [R = (t)Bu ( 1) and iPr ( 3)] were oxidized with elemental selenium. During these reactions an unexpected C–N bond cleavage and N–H bond formation occurred. Compound 1 produced P4(μ-N(t)Bu)3(μ-NH)3Se4 ( 2) where three tBu groups were lost in the form of isobutylene. In contrast, during the oxidation of the less sterically hindered 3, the resulting product, P4(μ-N(i)Pr)5(μ-NH)Se4 ( 4), showed only one substituent loss. Theoretical studies confirmed the steric nature of the driving force underlying the different outcomes.

ChemInform Abstract: Cleavage of the C=N Bond in Carbodiimides via Release of High Ring Strain: A New Strategy for the Selective Synthesis of 2‐Aminoaryl Alkynyl Imines.

AbstractA novel multicomponent reaction of terminal alkynes or haloalkynes, carbodiimides, and benzynes is achieved via cleavage and reorganization of C=N bond to efficiently obtain the title compounds.

Improved electrolyte and its application in LiNi1/3Mn1/3Co1/3O2–Graphite full cells

Lithium oxalatodifluoroborate (LiODFB) has been synthesized and used as a novel electrolyte additive. Standard and modified electrolytes were flame-sealed in NMR tubes and stored at 60 °C for 3 months. Multiple nuclear NMR (1H, 11B, 13C, 19F, 31P) studies confirmed that the modified electrolyte (2% LiODFB added) showed no signs of decomposition as that of regular electrolyte, which is possibly due to the –F of LiPF6 and oxalate of LiODFB ligand exchange effect. The high temperature stabilization mechanism of the added LiODFB was studied using quantum mechanical calculations. Electrochemical tests of LiNi1/3Mn1/3Co1/3O2 (NMC)–Graphite full-cells with and without LiODFB as the electrolyte additive were conducted. When cycling with the NMC–Graphite full-cell at elevated temperature (60 °C), the 100th cycle capacity retention rate of the modified electrolyte was 60%, compared to 27% with the standard electrolyte. The EIS study indicates the full-cells with LiODFB have much lower interfacial impedance than the standard cells. Theoretical calculations reveal that LiODFB generates a layer of thin and resilient SEI on the graphite surface at a higher reduction potential than ethylene carbonate (EC) due to its higher ring strain and protects graphite from the toxic Mn2+ resulting in improved electrochemical performance of NMC–Graphite based cells.

Oxaphosphirane-borane complexes: ring strain and migratory insertion/ring-opening reactions.

DFT-based HSAB-related parameters predict most favorable P- versus O-complexation of parent oxaphosphirane (1) with a variety of borane reagents BR3 (2). In general, strong P-B bonds are formed, especially for R: H (3a), Cl (3d), and C6F5 (3g), in agreement with large dissociation energies, whereas O-B bonds are usually weaker. A remarkable increase in ring strain is observed upon P-complexation of phosphirane or oxaphosphiranes, especially in the case of 3g and 3d, whereas a moderate decrease occurs in the case of O-complexation for both oxirane and oxaphosphiranes. Stronger P-B bonds also correlate with larger charge transfer from the oxaphosphirane to the borane units. This in turn increases electron density at the boron center and weakens all B-R bonds, thus enabling migratory insertion/ring-opening reactions in which a substituent from the borate center shifts to a ring atom; these reactions are additionally driven by release of the high ring strain of P-complexes 3.

A metallic carbon consisting of helical carbon triangle chains

Carbon is the basis of life on Earth and many technological applications. We computationally report an sp3-hybridization-assembled carbon allotrope constructed by helical triangle chains through the evolutionary structure prediction method. Different from the previous metallic carbon K4, this carbon, called Tri-carbon, is mechanically and dynamically stable at ambient pressure. High ring strain in the carbon triangle blocks forces the C–C bond in Tri-carbon to be a ‘bent bond’, rather than the common single bond in diamond or the π bond in graphite. Unlike the unstrained sp3-hybridization in semiconductive diamond, valence electrons in the ‘bent bond’ are recombined to form extremely anisotropic sp3-hybridized bonds, thus conferring metallicity to Tri-carbon. Under nonhydrostatic conditions, Tri-carbon shows significantly anisotropic ideal tensile and compressive strength. Tri-carbon is expected to be achieved through chemical methods, such as the synthesis of cyclopropane derivatives (e.g. triangulane and tetrahedrane). These methods eliminate the restriction of ultra-high pressure to obtain metallic carbons.