The synthesis of strained carbocyclic building blocks is relevant for Medicinal Chemistry, and methylenecyclobutanes are particularly challenging with current synthetic technology. Careful inspection of the reactivity of [1.1.1]propellane and diboron reagents has revealed that bis(catecholato)diboron (B2cat2) can produce a bis(borylated) methylenecyclobutane in a few minutes at room temperature. This reaction constitutes the first example of B-B bond activation by a special apolar hydrocarbon and also the first time that propellane is electrophilically activated by boron. Mechanistic studies including in situ NMR kinetics and DFT calculations demonstrate that the diboron moiety can be directly activated through coordination with the inverted sigma bond of propellane, and reveal that DMF is involved in the stabilization of diboronate ylide intermediates rather than the activation of the B-B bond. These results enable new possibilities for both diboron and propellane chemistry, and for further developments in the synthesis of methylenecyclobutanes based on propellane strain release.

In this review, the current state of affairs in the novel field of the group 14 element clusters based on the bicyclo[1.1.0]butane framework, namely, bicyclo[1.1.0]butane, [1.1.1]propellane, and tricyclo[2.1.0.02,5 ]pentane derivatives, are overviewed. Structural similarities and differences between these three classes of highly strained polycyclic compounds are considered from the viewpoint of the critically important nature of their bridgehead bonds. Synthetic strategies towards bicyclo[1.1.0]butanes, [1.1.1]propellanes, and tricyclo[2.1.0.02,5 ]pentanes, as well as their peculiar structural and bonding features, and specific reactivity, are also presented and discussed in this review.

Polymer dielectrics with high energy density are of urgent demand in electric and electronic devices, but the tradeoff between dielectric constant and breakdown strength is still unsolved. Herein, the synthesis and molar mass control of three alternating [1.1.1]propellane-(meth)acrylate copolymers, denoted as P-MA, P-MMA, and P-EA, respectively, are reported. These copolymers exhibit high thermal stability and are semi-crystalline with varied glass transition temperatures and melting temperatures. The rigid bicyclo[1.1.1]pentane units in the polymer backbone promote the orientational polarization of the polar ester groups, thus enhancing the dielectric constants of these polymers, which are 4.50 for P-EA, 4.55 for P-MA, and 5.11 for P-MMA at 10 Hz and room temperature, respectively. Moreover, the high breakdown strength is ensured by the non-conjugated nature of bicyclo[1.1.1]pentane unit. As a result, these copolymers show extraordinary energy storage performance; P-MA exhibits a discharge energy density of 9.73 J cm-3 at 750 MV m-1 and ambient temperature. This work provides a new type of promising candidates as polymer dielectrics for film capacitors, and offers an efficient strategy to improve the dielectric and energy storage properties by introducing rigid non-conjugated bicyclo[1.1.1]pentane unit into the polymer backbone.

Strategies commonly used for the synthesis of functionalised bicyclo[1.1.1]pentanes (BCP) rely on the reaction of [1.1.1]propellane with anionic or radical intermediates. In contrast, electrophilic activation has remained a considerable challenge due to the facile decomposition of BCP cations, which has severely limited the applications of this strategy. Herein, we report the electrophilic activation of [1.1.1]propellane in a halogen bond complex, which enables its reaction with electron-neutral nucleophiles such as anilines and azoles to give nitrogen-substituted BCPs that are prominent motifs in drug discovery. A detailed computational analysis indicates that the key halogen bonding interaction promotes nucleophilic attack without sacrificing cage stabilisation. Overall, our work rehabilitates electrophilic activation of [1.1.1]propellane as a valuable strategy for accessing functionalised BCPs.

The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α-cyclodextrin (α-CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3-diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non-polar solvents. The combination of these methodologies enables simple, on-demand preparation of [1.1.1]propellane in various solvents under mild conditions from α-CD capsules containing 1,3-diiodo BCP.

We report a range of highly regioselective openings of [1.1.1]propellane with various allylic zinc halides, as well as zinc enolates of ketones, esters and nitriles. The resulting zincated bicyclopentanes (BCPs) were trapped with a range of electrophiles including acyl chlorides, sulfonothioates, hydroxylamino benzoates, tosyl cyanide as well as aryl and allyl halides, generating highly functionalized BCP-derivatives. The unusually high regioselectivity of these reactions has been rationalized using DFT calculations. A bioisostere of the synthetic opioid pethidine was prepared in 95 % yield in one step using this method.

Inverted bonds: In this Correspondence, the authors comment on the recent paper on inverted bonds in [1.1.1]propellane by Chaquin et al.

1,3-Disubstituted bicyclo[1.1.1]pentanes (BCPs) are valuable bioisosteres of para-substituted aromatic rings. The most direct route to these structures is via multicomponent ring-opening reactions of [1.1.1]propellane. However, challenges associated with these transformations mean that difunctionalized BCPs are more commonly prepared by multistep reaction sequences with BCP-halide intermediates. Herein, we report three- and four-component 1,3-difunctionalizations of [1.1.1]propellane with organometallic reagents, organoboronic esters, and a variety of electrophiles. This process is achieved by trapping intermediate BCP-metal species with boronic esters to form boronate complexes, which are versatile intermediates whose electrophile-induced 1,2-metallate rearrangement chemistry enables a broad range of C-C bond-forming reactions.

This article dwells on the nature of \"inverted bonds\", which refer to the σ interaction between two sp hybrids by their smaller lobes, and their presence in [1.1.1]propellane. Firstly, we study H3 C-C models of C-C bonds with frozen H-C-C angles reproducing the constraints of various degrees of \"inversion\". Secondly, the molecular orbital (MO) properties of [1.1.1]propellane and [1.1.1]bicyclopentane are analyzed with the help of orbital forces as a criterion of bonding/antibonding character and as a basis to evaluate bond energies. Triplet and cationic states of [1.1.1]propellane species are also considered to confirm the bonding/antibonding character of MOs in the parent molecule. These approaches show an essentially non-bonding character of the σ central C-C interaction in propellane. Within the MO theory, this bonding is thus only due to π-type MOs (also called \"banana\" MOs or \"bridge\" MOs) and its total energy is evaluated to approximately 50 kcal mol-1 . In bicyclopentane, despite a strong σ-type repulsion, a weak bonding (15-20 kcal mol-1 ) exists between both central C-C bonds, also due to π-type interactions, though no bond is present in the Lewis structure. Overall, the so-called \"inverted\" bond, as resulting from a σ overlap of the two sp hybrids by their smaller lobes, appears highly questionable.

Herein we present the synthesis of symmetrically and unsymmetrically substituted 1,3-bissulfanylbicyclo[1.1.1]pentanes from disulfides and [1.1.1]propellane. Bicyclo[1.1.1]pentanes (BCPs) recently gained interest as rigid linkers and as bioisosters of para-substituted benzene and alkyne moieties. The most promising precursor for BCPs is [1.1.1]propellane (1). The available methods to synthesize BCPs are quite limited and many groups contribute to the development of novel methods. The insertion of 1 into disulfide bonds is known, but has never been thoroughly investigated. In this study, we show that an UV initiated radical reaction can be used to synthesize symmetrically and unsymmetrically substituted BCP sulfides by reaction of [1.1.1]propellane (1) with disulfides. Depending on the ratio of 1 to the disulfide, only the BCP product (with up to 98% yield) or a mixture of BCP and [2]staffane can be obtained. The reaction tolerates functional groups such as halogens, alkyl and methoxy groups. The separation of the corresponding BCP and [2]staffane products is challenging but possible by column chromatography and preparative TLC in most cases. Single crystal X-ray diffraction analysis confirms the rod-like structure of the [2]staffanes that is often required in material applications.