Homogenizing The Low-Dimensional Phases for Stable 2D-3D Tin Perovskite Solar Cells.

2D-3D tin-based perovskites are considered as promising candidates for achieving efficient lead-free perovskite solar cells (PSCs). However, the existence of multiple low-dimensional phases formed during the film preparation hinders the efficient transport of charge carriers. In addition, the non-homogeneous distribution of low-dimensional phases leads to lattice distortion and increases the defect density, which are undesirable for the stability of tin-based PSCs. Here, mixed spacer cations [diethylamine (DEA+) and phenethylamine (PEA+)] are introduced into tin perovskite films to modulate the distribution of the 2D phases. It is found that compared to the film with only PEA+, the combination of DEA+ and PEA+ favors the formation of homogeneous low-dimensional perovskite phases with three octahedral monolayers (n = 3), especially near the bottom interface between perovskite and hole transport layer. The homogenization of 2D phases help improve the film quality with reduced lattice distortion and released strain. With these merits, the tin PSC shows significantly improved stability with 94% of its initial efficiency retained after storing in a nitrogen atmosphere for over 4600 h, and over 80% efficiency maintained after continuous illumination for 400 h.

Overcoming a Radical Polarity Mismatch in Strain-Release Pentafluorosulfanylation of [1.1.0]Bicyclobutanes: An Entryway to Sulfone- and Carbonyl-Containing SF5-Cyclobutanes.

The first assortment of achiral pentafluorosulfanylated cyclobutanes (SF5-CBs) are now synthetically accessible through strain-release functionalization of [1.1.0]bicyclobutanes (BCBs) using SF5Cl. Methods for both chloropentafluorosulfanylation and hydropentafluorosulfanylation of sulfone-based BCBs are detailed herein, as well as proof-of-concept that the logic extends to tetrafluoro(aryl)sulfanylation, tetrafluoro(trifluoromethyl)sulfanylation, and three-component pentafluorosulfanylation reactions. The methods presented enable isolation of both syn and anti isomers of SF5-CBs, but we also demonstrate that this innate selectivity can be overridden in chloropentafluorosulfanylation; that is, an anti-stereoselective variant of SF5Cl addition across sulfone-based BCBs can be achieved by using inexpensive copper salt additives. Considering the SF5 group and CBs have been employed individually as nonclassical bioisosteres, structural aspects of these unique SF5-CB "hybrid isosteres" were then contextualized using SC-XRD. From a mechanistic standpoint, chloropentafluorosulfanylation ostensibly proceeds through a curious polarity mismatch addition of electrophilic SF5 radicals to the electrophilic sites of the BCBs. Upon examining carbonyl-containing BCBs, we also observed rare instances whereby radical addition to the 1-position of a BCB occurs. The nature of the key C(sp3)-SF5 bond formation step - among other mechanistic features of the methods we disclose - was investigated experimentally and with DFT calculations. Lastly, we demonstrate compatibility of SF5-CBs with various downstream functionalizations.

Molecular Editing of Pyrroles to Benzenes/Naphthalenes by N2O Deletion.

A molecular editing reaction for converting pyrrole rings into benzene rings through a sequential pathway of Diels-Alder and cheletropic reactions was developed. The nitrogen atom in a N-bridged intermediate is eliminated in the form of N2O by a strain-releasing pathway, ultimately leading to the formation of substituted benzene and naphthalene derivatives.

Silver-Enabled Cycloaddition of Bicyclobutanes with Isocyanides for the Synthesis of Polysubstituted 3-Azabicyclo[3.1.1]heptanes.

Synthesis of bicyclic scaffolds has emerged as an important research topic in modern drug development because they can serve as saturated bioisosters to enhance the physicochemical properties and metabolic profiles of drug candidates. Here we report a remarkably simple silver-enabled strategy to access polysubstituted 3-azabicyclo[3.1.1]heptanes in a single operation from readily accessible bicyclobutanes (BCBs) and isocyanides. The process is proposed to involve a formal (3+3)/(3+2)/retro-(3+2) cycloaddition sequence. This novel protocol allows for rapid generation of molecular complexity from simple starting materials, and the products can be easily derivatized, further enriching the BCB cycloaddition chemistry and the growing set of valuable sp3-rich bicyclic building blocks.

Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2-Amino-bicyclo[2.1.1]hexenes.

Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)3-catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2-amino-bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB-based cycloaddition chemistry.

Lewis Acid-Catalyzed Unusual (4+3) Annulation of para-Quinone Methides with Bicyclobutanes: Access to Oxabicyclo[4.1.1]Octanes.

Over the past few years, there has been a surge of interest in the chemistry of bicyclobutanes (BCBs). Although BCBs have been used to synthesize bicyclo[2.1.1]hexanes and bicyclo[3.1.1]heptanes, the synthesis of bicyclo[4.1.1]octanes has remained elusive. Herein, we report the first Lewis acid-catalyzed unexpected (4+3) annulation of para-quinonemethides (p-QMs) with BCBs allowing the synthesis of oxabicyclo[4.1.1]octanes proceeding under mild conditions. With 5 mol % of Bi(OTf)3, the reaction afforded the (4+3) annulated product in high regioselectivity and good functional group compatibility via a simultaneous Lewis acid activation of BCBs and p-QMs. The reaction is likely initiated by the 1,6-addition of Lewis acid activated BCBs to p-QMs followed by the C2-selective intramolecular addition of the phenol moiety to the generated cyclobutyl cation intermediate. Moreover, detailed mechanistic studies provided insight into the mechanism of the reaction.

Expedient synthesis of spiro[3.3]heptan-1-ones via strain-relocating semipinacol rearrangements.

A novel approach for the formation of the highly strained spiro[3.3]heptan-1-one motif was developed through the reaction of 1-sulfonylcyclopropanols and lithiated 1-sulfonylbicyclo[1.1.0]butanes. Following initial nucleophilic addition to the cyclopropanone formed in situ, the resulting 1-bicyclobutylcyclopropanol intermediate is prone to a 'strain-relocating' semipinacol rearrangement in the presence of acid, directly affording the substituted spiro[3.3]heptan-1-one. The process is shown to be fully regio- and stereospecific when starting from a substituted cyclopropanone equivalent, leading to optically active 3-substituted spiro[3.3]heptan-1-ones. The reaction likely proceeds via initial protonation of the bicyclobutyl moiety followed by [1,2]-rearrangement of the resulting cyclopropylcarbinyl cation.

Synthesis of 2-Azanorbornanes via Strain-Release Formal Cycloadditions Initiated by Energy Transfer.

Rigid bicycles are becoming more popular in the pharmaceutical industry because they allow for expansion to new and unique chemical spaces. This work describes a new strategy to construct 2-azanorbornanes, which can act as rigid piperidine/pyrrolidine scaffolds with well-defined exit vectors. To achieve the synthesis of 2-azanorbornanes, new strain-release reagent, azahousane, is introduced along with its photosensitized strain-release formal cycloaddition with alkenes. Furthermore, new reactivity between a housane and an imine is disclosed. Both strategies lead to various substituted 2-azanorbornanes with good selectivities.

Photocatalytic C-C Cleavage of Methylenecyclobutanes for γ,δ-Unsaturated Aldehydes by Strain Release.

Radical additions onto olefins have surfaced as an increasingly powerful strategy for the synthesis of difunctionalized scaffolds. However, despite of major advances, known approaches continue to be largely limited to two manifolds, namely 1,2-difunctionalization of alkenes and remote difunctionalization via hydrogen atom transfer (HAT). Herein, we describe a mechanistically distinct approach by photoinduced carbon-carbon (C-C) activation/ring-opening to access γ,δ-unsaturated aldehydes from methylenecyclobutanols and sulfonyl chlorides by strain release. Remarkably, the sulfonyl motif on the products was easily removed by another photocatalytic process, which enabled the concise assembly of the natural product alatanone A. The synthetic utility of our approach was reflected by versatile functional group tolerance, ample substrate scope, and scalability. The photocatalysis represents a conceptually distinct alternative to existing approaches for remote 1,4-diversifications, with a double bond remaining in the thus obtained products.

Catalytic Formal [2π+2σ] Cycloaddition of Aldehydes with Bicyclobutanes: Expedient Access to Polysubstituted 2-Oxabicyclo[2.1.1]hexanes.

Synthesis of bicyclic scaffolds has attracted tremendous attention because they are playing an important role as saturated bioisosteres of benzenoids in modern drug discovery. Here, we report a BF3 -catalyzed [2π+2σ] cycloaddition of aldehydes with bicyclo[1.1.0]butanes (BCBs) to access polysubstituted 2-oxabicyclo[2.1.1]hexanes. A new kind of BCB containing an acyl pyrazole group was invented, which not only significantly facilitates the reactions, but can also serve as a handle for diverse downstream transformations. Furthermore, aryl and vinyl epoxides can also be utilized as substrates which undergo cycloaddition with BCBs after in situ rearrangement to aldehydes. We anticipate that our results will promote access to challenging sp3 -rich bicyclic frameworks and the exploration of BCB-based cycloaddition chemistry.

Cation-Promoted Strain-Release-Driven Access to Functionalized Azetidines from Azabicyclo[1.1.0]butanes.

Access to 1,3-functionalized azetidines through a diversity-oriented approach is highly sought-after for finding new applications in drug-discovery. To this goal, strain-release-driven functionalization of azabicyclo[1.1.0]-butane (ABB) has generated significant interest. Through appropriate N-activation, C3-substituted ABBs are shown to render tandem N/C3-fucntionalization/rearrangement, furnishing azetidines; although, modalities of such N-activation vis-à-vis N-functionalization remain limited to selected electrophiles. This work showcases a versatile cation-driven activation strategy of ABBs. And capitalizes on the use of Csp3 precursors amenable to forming reactive (aza)oxyallyl cations in situ. Herein, N-activation leads to formation of a congested C-N bond, and effective C3 activation. The concept was extended to formal [3+2] annulations involving (aza)oxyallyl cations and ABBs, leading to bridged bicyclic azetidines. Besides the fundamental appeal of this new activation paradigm, operational simplicity and remarkable diversity should engender its prompt use in synthetic and medicinal chemistry.

Switchable and Strain-Releasable Mg-Ion Diffusion Nanohighway Enables High-Capacity and Long-Life Pyrovanadate Cathode.

Rechargeable magnesium batteries (RMBs) suffer from low capacity and poor cyclability of cathode materials, which is due to the sluggish Mg2+ diffusion kinetics and large lattice strain. Here, a layer-interweaving mechanism in lamellar cathode to simultaneously facilitate Mg2+ diffusion and release Mg2+ -insertion strain is reported. In the Cu3 V2 O7 (OH)2 ·2H2 O (CVOH) cathode, Mg2+ diffusion highways are generated by the vertical interweaving of CVOH layers and V6 O13 layers that nucleate in CVOH during discharging, which are switchable by Mg2+ insertion/extraction. These highways enhance the Mg2+ diffusion coefficient by three orders of magnitude and release 50% Mg2+ -insertion strain. This enables CVOH to exhibit a high capacity of 262 mAh g-1 at high current density of 250 mA g-1 in aqua, and extremely low capacity loss of 0.0004% per cycle in the activated carbon//CVOH cell. This work inspires designing the magnesiation phase transformation of electrodes to resolve both kinetic and strain issues for high-performance RMBs.

Vinylcyclopropane [3+2] Cycloaddition with Acetylenic Sulfones Based on Visible Light Photocatalysis.

The first intermolecular visible light [3+2] cycloaddition reaction performed on a meta photocycloadduct employing acetylenic sulfones is described. The developed methodology exploits the advantages of combining UV and visible-light in a two-step sequence that provides a photogenerated cyclopropane which, through a strain-release process, generates a new cyclopentane ring while significantly increasing the molecular complexity. Mechanistic studies and DFT calculations indicate an energy transfer pathway for the visible light-driven reaction step. This strategy could be extended to simpler vinylcyclopropanes.

Beyond Bioisosteres: Divergent Synthesis of Azabicyclohexanes and Cyclobutenyl Amines from Bicyclobutanes.

The development of two divergent and complementary Lewis acid catalyzed additions of bicyclobutanes to imines is described. Microscale high-throughput experimentation was integral to the discovery and optimization of both reactions. N-arylimines undergo formal (3+2) cycloaddition with bicyclobutanes to yield azabicyclo[2.1.1]hexanes in a single step; in contrast, N-alkylimines undergo an addition/elimination sequence to generate cyclobutenyl methanamine products with high diastereoselectivity. These new products contain a variety of synthetic handles for further elaboration, including many functional groups relevant to pharmaceutical synthesis. The divergent reactivity observed is attributed to differences in basicity and nucleophilicity of the nitrogen atom in a common carbocation intermediate, leading to either nucleophilic attack (N-aryl) or E1 elimination (N-alkyl).

Palladium-Catalyzed Stagewise Strain-Release-Driven C-C Activation of Bicyclo[1.1.1]pentanyl Alcohols.

A palladium-catalyzed chemoselective coupling of readily available bicyclo[1.1.1]pentanyl alcohols (BCP-OH) with various halides is reported, which offers expedient approaches to a wide range of cyclobutanone and ß,γ-enone skeletons via single or double C-C activation. The chemistry shows a broad substrate scope in terms of both the range of BCP-OH and halides including a series of natural product derivatives. Moreover, dependency of reaction chemodivergence on base additive has been investigated through experimental and density functional theory (DFT) studies, which is expected to significantly enrich the reaction modes and increase the synthetic potential of BCP-OH in preparing more complex molecules.

Strain Release Chemistry of Photogenerated Small-Ring Intermediates.

Photochemical processes, such as isomerizations and cycloadditions, have proven to be very useful in the construction of highly strained molecular frameworks. Photoinduced ring strain enables subsequent exergonic reactions which do not require the input of additional chemical energy and provides a variety of attractive synthetic options leading to complex structures. This review covers the progress achieved in the application of sequences combining excitation by ultraviolet light to form strained intermediates, which are further transformed to lower energy products in strain-release reactions. As ring strain is considerable in small ring systems, photogenerated three- and four-membered rings will be covered, mainly focusing on examples from 2000 to May 2020.

α-Selective Ring-Opening Reactions of Bicyclo[1.1.0]butyl Boronic Ester with Nucleophiles.

The reaction of bicyclo[1.1.0]butyl pinacol boronic ester (BCB-Bpin) with nucleophiles has been studied. Unlike BCBs bearing electron-withdrawing groups, which react with nucleophiles at the ß-position, BCB-Bpin reacts with a diverse set of heteroatom (O, S, N)-centred nucleophiles exclusively at the α-position. Aliphatic alcohols, phenols, carboxylic acids, thiols and sulfonamides were found to be competent nucleophiles, providing ready access to α-heteroatom-substituted cyclobutyl boronic esters. In contrast, sterically hindered bis-sulfonamides and related nucleophiles reacted with BCB-Bpin at the ß'-position leading to cyclopropanes with high trans-selectivity. The origin of selectivity is discussed.

Divergent Strain-Release Amino-Functionalization of [1.1.1]Propellane with Electrophilic Nitrogen-Radicals.

Herein we report the development of a photocatalytic strategy for the divergent preparation of functionalized bicyclo[1.1.1]pentylamines. This approach exploits, for the first time, the ability of nitrogen-radicals to undergo strain-release reaction with [1.1.1]propellane. This reactivity is facilitated by the electrophilic nature of these open-shell intermediates and the presence of strong polar effects in the transition-state for C-N bond formation/ring-opening. With the aid of a simple reductive quenching photoredox cycle, we have successfully harnessed this novel radical strain-release amination as part of a multicomponent cascade compatible with several external trapping agents. Overall, this radical strategy enables the rapid construction of novel amino-functionalized building blocks with potential application in medicinal chemistry programs as p-substituted aniline bioisosteres.

Organocatalytic Regiodivergent C-C Bond Cleavage of Cyclopropenones: A Highly Efficient Cascade Approach to Enantiopure Heterocyclic Frameworks.

Here a highly efficient cascade approach is reported that combines a cycloaddition reaction with a regioselective strain-release process to afford diverse heterocyclic frameworks through bifunctional catalysis. The cooperation of hydrogen-bonding network activation and a regiodivergent strain-assisted effect is the key to promoting this complex chemical transformation, leading to the generation of two different ring systems in high yields with excellent stereoselectivities. The reaction proceeded by a mechanism involving a "spring-loaded" intermediate with switchable C-C bond cleavages achieved by controllable ring-strain release. This reaction was also amenable to gram scale synthesis with only 0.1 mol % catalyst loading.

Malolactone strikes: K-Ras-G12D's Achilles' heel.

In a recent study in Nature Chemical Biology, Zheng et al. exploiting strain release by malolactone-based electrophiles designed a first-in-class covalent inhibitor that targets the elusive aspartate of the Kirsten rat sarcoma viral oncogene homolog (K-Ras)-G12D variant, which is highly prevalent in pancreatic cancer. The compound drastically inhibited oncogenic signaling and tumor growth in preclinical K-Ras-G12D-mutant pancreatic cancer models, expanding treatment potential beyond K-Ras-G12C-targeted therapies.