Search

The first Ficini reaction between ynamides and acrylates is reported herein. The reaction is catalyzed by B(C6F5)3 acting as a Lewis acid and is giving access to stable tri‐substituted aminocyclobutenes in high yield. The resulting products can be hydrogenated and epimerized under basic conditions or in presence of a Lewis acid, providing two distinct trans‐ aminocyclobutane monoester stereoisomers in high yield and diastereoisomeric ratio (up to quantitative yield and >99 : 1 dr). [ABSTRACT FROM AUTHOR]

Capitalizing the inherent strain energy within molecules, strain‐release‐driven reactions have been widely employed in organic synthesis. Small cycloalkanes like cyclopropanes and cyclobutanes, with their moderate ring strain, typically require dense functionalization to induce bias or distal activation of (hetero) aromatic rings via single‐electron oxidation for relieving the tension. In this study, we present a pioneering direct activation of alkyl cyclopropanes/butanes through electrochemical oxidation. This approach not only showcases the potential for ring‐opening of cyclopropane/butane under electrochemical conditions but also streamlines the synthesis of diverse oxazolines and oxazines. The applicability of our method is exemplified by its broad substrate scopes. Notably, the products derived from cyclobutanes undergo a formal ring contraction to cyclopropanes, introducing an intriguing aspect to our discoveries. These discoveries mark a significant advancement in strain‐release‐driven skeletal rearrangement reactions of moderately strained rings, offering sustainable and efficient synthetic pathways for future endeavours. [ABSTRACT FROM AUTHOR]

Cyclobutanes are popular structural units in bioactive compounds and versatile intermediates in synthetic chemistry, but their synthesis is challenging owing to high ring strain. In this study, a novel method for highly regio‐ and diastereoselective synthesis of fluoroalkylcyclobutanes bearing vicinal quaternary and tertiary stereocenters is realized by a photocatalytic 4‐exo‐trig cyclization cascade of thioalkynes or trifluoromethylalkenes. Density functional theory calculations reveal that a unique fluorine effect, arising from hyperconjugative π→σ*C‐F interactions, accounts for the regio‐reversed radical addition at the sterically hindered alkene carbon, which facilitates an unprecedented 4‐exo‐trig ring closure. This chemistry enables the direct and controllable construction of medicinally valuable quaternary‐carbon‐containing cyclobutanes from readily available raw materials, nicely complementing the existing methods. [ABSTRACT FROM AUTHOR]

In order to expand the knowledge on linear alicyclic musks, a set of 29 small‐ring (racemic) analogues of the biodegradable and renewable alicyclic musk Romandolide was designed, prepared, and evaluated. The common short and modular synthesis employs either commercially available or easily accessible (substituted) cyclopropyl/cyclobutyl ketones and acids. These were transformed in three/four steps to the target compounds. Their qualitative olfactory analysis reveals that contraction of cyclohexane ring of Romandolide to smaller rings annihilates the genuine musk scent, though many of these share the metallic hot‐iron off‐note of some macrocyclic musks. Indeed, these new derivatives exhibit a plethora of pleasant, interesting, and potentially useful scents including herbal, green, fruity, or chocolate ones accompanied by various undertones. The powdery, fruity ionone odor of the dimethyl cyclobutyl compound was found to be most interesting as it possesses a very natural raspberry and violet character. Computational modelling suggest that the lowest‐energy conformers of the target compounds do either not adopt a true U‐shape as was speculated to be a prerequisite for a musk odor, or that the quaternary carbon atom of the dimethyl‐substituted cyclobutane is not well placed to fit into a hydrophobic binding pocket on the corresponding receptor site. [ABSTRACT FROM AUTHOR]

Electrophilic groups are one of the key pillars of contemporary chemical biology and medicinal chemistry. For instance, 3‐membered N‐heterocyclic compounds—such as aziridines, azirines, and oxaziridines—possess unique electronic and structural properties which underlie their potential and applicability as covalent tools. The α‐lactams are also members of this group of compounds, however, their utility within the field remains unexplored. Here, we demonstrate an α‐lactam reagent (AM2) that is tolerant to aqueous buffers while being reactive towards biologically relevant nucleophiles. Interestingly, carboxylesterases 1 and 2 (CES1/2), both serine hydrolases with key roles in endo‐ and xenobiotic metabolism, were found as primary covalent targets for AM2 in HepG2 liver cancer cells. All in all, this study constitutes the starting point for the further development and exploration of α‐lactam‐based electrophilic probes in covalent chemical biology. [ABSTRACT FROM AUTHOR]

A stereoselective one‐pot double derivatization of cyclobutene‐1‐carboxylic acid via a mild organic base catalyzed amidation/aza‐Michael addition of benzo[d]oxazol‐2(3H)‐ones has been developed. This unprecedented tandem reaction provides access to novel β‐N‐heterocyclic cyclobutane carboximide derivatives with a trans geometry. The carboximide moiety reacts smoothly with nucleophiles, allowing access to diverse derivatives of trans‐β‐N‐heterocyclic cyclobutanecarboxylic acid, including peptidomimetic structures. [ABSTRACT FROM AUTHOR]

The ring‐opening reaction of nitro‐substituted donor‐acceptor cyclopropanes with pyrazoles in DMSO was investigated. Unexpectedly, the cyclopropanes underwent Kornblum‐type ring‐opening oxidation with DMSO to form aroylmethylidene malonates as intermediates in the reactions. The intermediates further underwent aza‐Michael addition with pyrazoles in tandem manner to give the corresponding aza‐Michael adducts. The highlights of the methodology include the occurrence of ring‐opening/oxidation under neutral conditions with DMSO and formation of aza‐Michael adducts with pyrazoles under catalyst‐free conditions. [ABSTRACT FROM AUTHOR]

Quantum mechanical tunneling has long been recognized as an important phenomenon when considering transformations dominated by a lightweight hydrogen atom. Tunneling of heavier atoms like carbon, initially dismissed as negligible, has seen a quickly increasing number of computationally predicted and/or experimentally confirmed examples over the last decade, thus highlighting its importance for a wide variety of reactions. However, no common structural motif has been pointed out within these seemingly unconnected examples, strongly limiting the predictability of the impact of heavy‐atom tunneling on a given reaction. This Concept article will provide this perspective and showcase how the recognition of the formation and cleavage of three‐membered rings as common motif can inform the prediction of and research into heavy‐atom tunneling reactions. [ABSTRACT FROM AUTHOR]

Asymmetric de novo synthesis of benzocyclobutenes (BCBs) via catalytic intermolecular reaction is highly desired for efficient access to this important class of compounds, yet such a strategy remains unmet challenge. Here, we report a Pd/Pyrox-catalyzed asymmetric [2+2] annulation between arylboronic acids and functionalized alkenes, providing an unprecedented efficient protocol to access various enantio-enriched BCBs in a modular and versatile manner under mild conditions. A broad substrate scope with excellent enantioselectivity has been achieved under the current protocol. The isolation and characterization of the key chiral palladacycle intermediate, together with DFT calculations, provides strong evidence for the catalytic pathway including an enantiodetermining arylpalladation step., (© 2024 Wiley‐VCH GmbH.)

We report a procedure for the multigram synthesis of 4‐(dimethylamino)pyridinium azide, a stable, non‐explosive, low‐hygroscopic source of azide ion soluble in both protic and aprotic organic solvents. In protic ionic liquid media this reagent was shown to serve as a safer equivalent of toxic and unstable hydrazoic acid. The synthetic utility of this system was demonstrated using donor‐acceptor cyclopropane ring opening as a model process. General procedures furnishing a variety of dialkyl (2‐azido‐2‐arylethyl)malonates or 4‐azido‐4‐arylbutyrates, depending on the protic ionic liquid applied, were elaborated. The conversion times for studied donor‐acceptor cyclopropanes were established providing the relative reactivity sequence. The application of 4‐(dimethylamino)pyridinium azide for a conventional nucleophilic substitution, oxirane ring opening, (3+2)‐cycloaddition to (thio)cyano group as well as their combinations realized as telescopic synthesis was also demonstrated. [ABSTRACT FROM AUTHOR]

A series of highly‐fluorinated triaminocyclopropenium salts, with up to six fluorous groups, were prepared and their properties as ionic liquids investigated. Reaction of pentachlorocyclopropane or tetrachlorocyclopropene with bis(2,2,2‐trifluoroethyl)amine, HN(CH2CF3)2, occurs in the presence of a trialkylamine, NR3, to give cations with two fluorinated amino groups, [C3(N(CH2CF3)2)2(NR2)]+ (R=Et, Pr, Bu, Hex), with traces of [C3(N(CH2CF3)2)3]+. Use of appropriate reagent ratios and reaction times and subsequent addition of a dialkylamine, HNR'R", gives cations with one fluorinated amino group, [C3(N(CH2CF3)2)(NR2)(NR'R")]+ ((NR2)(NR'R")=(NBu2)2, (NEt2)(NPr2), (NBu2)(NBuMe)). These cations were isolated as chloride salts and some of these were converted to bistriflamide, dicyanamide and triflate salts to provide ionic liquids. These salts were characterised by thermal (DSC and TGA) measurements and miscibility/solubility properties (determined in a range of solvents). Ionic liquids (ILs) were also characterised by density, viscosity and conductivity measurements where possible. X‐ray diffraction studies of chloride salts showed the formation of fluorous regions and more hydrophilic ionic regions in the solid state. [ABSTRACT FROM AUTHOR]

The empirical linear scaling dependencies between the literature (ΔrHo(Xn,TAB)) and the calculated (ΔrHo((Xn)i,CALC)) values of atomization of 31 reference aromatic and related compounds (T=298.15 K), as well as their standard errors ((SE4)i≅(σ4)i, Stand.Dev.), are determined for the different quantum mechanical (QMi) approaches. These dependencies are compared and used for the determination of the values of ΔrHo((Xn)i,CORRE)±3(SE4)i of atomization reactions of considered not reference aromatic compounds, as well as for the determination of their values of ΔfHo((Xn)i,CORRE)±3(SE4)i. The values of ΔfHo((Xn)i,CORRE)MEAN±3SEYE (≥99.4 % confidence interval), determined using the intersections of the 3(SE4)i intervals, are consistent with all QMi approaches and their literature values. The M06‐2X/6–311++G(d,p), M08HX/6–311++G(d,p) and wB97XD/6–311++G(d,p) approaches are recommended for the achievement of accuracy (SEYE)≤3.8 kJ/mol of the calculated values of ΔfHo((Xn)i,CORRE)MEAN. The effects of the number of O−H groups, size and multiplicity of compounds on values of error, also studied in this work, demonstrate the limitations of using of several scaled dependencies. [ABSTRACT FROM AUTHOR]

A convenient methodology for constructing 6,6‐difluorospiro[3.3]heptane scaffold – a conformationally restricted isoster of gem‐difluorocycloalkanes – is developed. A large array of novel 2‐mono‐ and 2,2‐bifunctionalized difluorospiro[3.3]heptane building blocks was obtained through the convergent synthesis strategy using a common synthetic precursor – 1,1‐bis(bromomethyl)‐3,3‐difluorocyclobutane. The target compounds and intermediates were prepared by short reaction sequences (6–10 steps) on a multigram scale (up to 0.47 kg). [ABSTRACT FROM AUTHOR]

Using the AlI precursor Cp3tAl in conjunction with triphosphiranes (PAr)3 (Ar=Mes, Dip, Tip) we have succeeded in preparing Lewis base‐free cyclic diphosphadialanes with both the Al and P atoms bearing three substituents. Using the sterically more demanding Dip and Tip substituents the first 1,2‐diphospha‐3,4‐dialuminacyclobutanes were obtained, whereas with Mes substituents [Cp3tAl(μ‐PMes)]2 is formed. This divergent reactivity was corroborated by DFT studies, which indicated the thermodynamic preference for the 1,2‐diphospha‐3,4‐dialuminacyclobutane form for sterically more demanding groups on phosphorus. Using Cp*Al we could extend this concept to the corresponding cyclic diarsadialanes [Cp*Al(μ‐AsAr)]2 (Ar=Dip, Tip) and additionally add the phosphorus variants [Cp*Al(μ‐PAr)]2 (P=Mes, Dip, Tip). The reactivity of one variant [Cp3tAl(μ‐PPh)]2 towards NHCs was tested and resulted in double NHC‐stabilised [Cp3t(IiPr2)Al(μ‐PPh)]2. [ABSTRACT FROM AUTHOR]

The present work describes the preparation of halohydrins from 2‐halocyclobutanones by means of reactions with Grignard reagents at −78 °C. We discovered that the prepared cyclobutanols underwent a thermal ring‐opening reaction. Depending on the structure of the starting cyclobutanol, different products were formed. More specifically, 1‐substituted 2‐bromocyclobutan‐1‐ol was found to open to γ‐substituted butyrophenones. A novel 1,3‐dihydro‐2H‐inden‐2‐ylidene derivative was obtained for indene‐derived cyclobutanols. Based on the outcomes of the performed experiments, a mechanism for the ring‐opening of cyclobutanols can be proposed. [ABSTRACT FROM AUTHOR]

The ultrafast photo‐induced ring opening of the oxirane derivative trans‐stilbene oxide has been studied through the use of ultrafast UV/UV pump‐probe spectroscopy by using photo‐ion detection. Single‐ and multiphoton probe paths and final states were identified through comparisons between UV power studies and synchrotron‐based vacuum ultraviolet (VUV) single‐photon ionization studies. Three major time‐dependent features of the parent ion (sub‐450 fs decay, (1.5±0.2) ps, and >100 ps) were observed. These decays are discussed in conjunction with the primary ring‐opening mechanism of stilbene oxide, which occurs through C−C dissociation in the oxirane ring. The appearance of fragments relating to the masses of dehydrogenated diphenylmethane (167 amu) and dehydrogenated methylbenzene (90 amu) were also investigated. The appearance of the 167 amu fragment could suggest an alternative ultrafast ring‐opening pathway via the dissociation of one of the C−O bonds within the oxirane ring. [ABSTRACT FROM AUTHOR]

We propose a new concept of the triple role of protic ionic liquids with nucleophilic anions: a) a regenerable solvent, b) a Brønsted acid inducing diverse transformations via general acid catalysis, and c) a source of a nucleophile. The efficiency of this strategy was demonstrated using thiocyanate‐based protic ionic liquids for the ring‐opening of donor‐acceptor cyclopropanes. A wide variety of activated cyclopropanes were found to react with 1‐methylimidazolium thiocyanate under mild metal‐free conditions via unusual nitrogen attack of the ambident thiocyanate ion on the electrophilic center of the three‐membered ring affording pyrrolidine‐2‐thiones bearing donor and acceptor substituents at the C(5) and C(3) atoms, respectively, in a single time‐efficient step. The ability of 1‐methylimidazolium thiocyanate to serve as a triplex reagent was exemplarily illustrated by (4+2)‐annulation with 1‐acyl‐2‐(2‐hydroxyphenyl)cyclopropane, epoxide ring‐opening and other organic transformations. [ABSTRACT FROM AUTHOR]

We present a Lewis acid catalyzed nucleophilic ring‐opening of donor‐acceptor cyclopropanes and ‐butanes by sydnones, utilizing their respective 1,3‐ and 1,4‐reactivity. The same conditions can be applied for the addition of sydnones to Michael acceptors. We propose a Friedel‐Crafts like mechanism. The reaction provides a rare, low‐temperature, transition metal‐free, and functional group tolerant protocol for the late‐stage functionalization of these mesoionic compounds of emerging importance in catalysis and bio‐orthogonal chemistry. [ABSTRACT FROM AUTHOR]

Azetidinones and β‐amino acids serve as useful building blocks in synthetic organic chemistry and their structural motifs are often found in biologically active compounds. Due to the importance of these compounds, several synthetic strategies have been developed and availability of new synthetic approaches is highly desirable. In this account, we describe the development of an original method that allows the preparation of β‐lactam and β‐homoproline derivatives not easily accessible through traditional processes. The serendipitous discovery made in our lab in 2000 involved the formation of a β‐lactam by heating a mixture of an alkylidenecyclopropane tethered to a formyl group with N‐methylhydroxylamine hydrochloride. Investigation of the process resulted in disclosing an alternative synthetic method of azetidinones based on an acid induced fragmentative rearrangement of cycloadducts of nitrones with suitable methylenecyclopropane derivatives. Herein, the scope of this process is reviewed. In addition, both experimental and computational studies of the mechanism for this peculiar fragmentative rearrangement are presented. [ABSTRACT FROM AUTHOR]

Sulfamide compounds are an important class of motif in various applications in pharmaceutical agents, agriculture, and material science. In this review, various synthetic strategies toward acyclic and cyclic sulfamide compounds utilizing many different methods are described. Herein, efficient and innovative synthetic methods ranging from small molecules to large rings for bioactive compounds, small molecules, and catalyst development are discussed. [ABSTRACT FROM AUTHOR]

The ladderane family of natural products are well known for their linearly concatenated cyclobutane skeletal structure. Owing to their unique carbocyclic framework, several chemical syntheses have been reported since their discovery in 2002. The focus of this review is to showcase the novel tactics that have been used to generate the ladderane core and the challenges that are associated with the synthesis of these unusual and complex natural products. [ABSTRACT FROM AUTHOR]

1,1,2,2‐Tetracyanocyclopropane derivatives 1 and 2 were designed and synthesized to probe the utility of sp3‐C centred tetrel bonding interactions in crystal engineering. The crystal packing of 1 and 2 and their 1,4‐dioxane cocrystals is dominated by sp3‐C(CN)2⋅⋅⋅O interactions, has significant C⋅⋅⋅O van der Waals overlap (≤0.266 Å) and DFT calculations indicate interaction energies of up to −11.0 kcal mol−1. A cocrystal of 2 with 1,4‐thioxane reveals that the cyclopropane synthon prefers interacting with O over S. Computational analyses revealed that the electropositive C2(CN)4 pocket in 1 and 2 can be seen as a strongly directional 'tetrel‐bond donor', similar to halogen bond or hydrogen bond donors. This disclosure is expected to have implications for the utility of such 'tetrel bond donors' in molecular disciplines such as crystal engineering, supramolecular chemistry, molecular recognition and medicinal chemistry. [ABSTRACT FROM AUTHOR]

A novel semipinacol rearrangement using dibromocyclopropanes as sources of carbocations was developed. Heating dibromocyclopropanes bearing a 1-hydroxyalkyl group with silver perchlorate and 2,6-lutidine induced cleavage of the cyclopropane ring to form allyl cations, which underwent 1,2- shift of a substituent at the α-position of the hydroxy group to give β,γ-unsaturated carbonyl compounds having a quaternary carbon at the α-position. Because the products have convertible functional groups such as bromo, vinyl, and formyl groups, the method is expected to be applicable to the synthesis of various molecules. [ABSTRACT FROM AUTHOR]

A range of protic triaminocyclopropenium salts with cations of the general formula [C3(NR2)2(NR'H)]+ (R=Me, Et; R'=H, Et, Pr, Bu, Pe, Hex, allyl, CH2CH2OMe) have been prepared by treatment of diaminoalkoxycyclopropenium salts with primary amines. Most salts were prepared with the bistriflamide anion, but the cation [C3(NEt2)2(NBuH)]+ was also combined with methylsulfate, dicyanamide, and tetrafluoroborate. The triprotic ionic liquid (IL) [C3(NPhH)3]NTf2 was also prepared and characterized. These protic ILs are characterised by thermal (DSC and TGA), density, viscosity and conductivity. The miscibility/solubility studies of these protic ILs has been determined in range of polar and non‐polar organic solvents. Comparisons have been made with similar series of aprotic bistriflamide (NTf2–) and dicyanamide (DCA) salts that have been reported previously. [ABSTRACT FROM AUTHOR]

Targeting the synthesis of Al/C based ambiphilic molecules, we investigated the dehydrohalogenation of a series of (benz)imidazole alane adducts. Depending on the steric bulk of the heterocycle, different dimeric products with various ring sizes were obtained. Dehydrohalogenation of the adduct of 1‐mesityl imidazole (MesIm) and 0.5 [tBu2AlBr]2 furnished the dimer 2, featuring a "classical" N‐heterocyclic carbene (NHC) and a mesoionic or "abnormal" NHC (aNHC) subunit within a single molecule. The dimer is bound loosely enough to allow thermally induced isomerization of 2 into the isomers 2NHC (all NHC) and 2aNHC (all aNHC). Dehydrohalogenation of the adduct of 1‐mesityl‐2‐methyl imidazole (MesImMe) and 0.5 [tBu2AlBr]2 (4) yielded the dimeric compound 5 consisting of two N‐heterocyclic olefin (NHO) subunits. Although these six‐ and eight‐membered heterocycles show no FLP‐type reactivity towards small molecules like H2, CO or CO2, we observed an ambiphilic behavior of the imidazolyl alanes during our studies. Salt metathesis reactions using MesIm resulted in the formation of 3, which can be viewed as tBu2AlBr adduct of an Al/N ambiphile. Utilizing heterocycles such as benzimidazole or spiroindole provided the entry point to C–H (7, 9) and N–H (10) activation products, most likely resulting from a reactivity of intermediate species as Al/C ambiphiles. [ABSTRACT FROM AUTHOR]

In contrast to cyclic π‐conjugated hydrocarbons, the coordination chemistry of inorganic heterocycles is less developed. Dicarbondiphosphides stabilized by N‐heterocyclic carbenes (NHCs) NHC→C2P2←NHC (1 a,b) (NHC=IPr or SIPr) contain a four‐membered C2P2 ring with an aromatic 6π‐electron configuration. These heterocycles coordinate to a variety of complex fragments with metals from groups 6, 9, and 10, namely [M0(CO)3] (M=Cr, Mo), [CoI(CO)2]+, or [NiIIBr2], through an η4‐coordination mode, leading to complexes 2 a,b, 3 a,b, 5 a,b, and 6 a,b, respectively. These complexes were characterized by X‐ray diffraction methods using single crystals, IR spectroscopy, and DFT calculations. In combination these methods indicate that 1 a,b behave as exceptionally strong 6π‐electron donors. [ABSTRACT FROM AUTHOR]

The diastereoselective synthesis of tetrasubstituted cyclopropanes is described. The two‐step procedure is based on the 3‐exo‐tet Michael addition‐initiated ring closure. In the first step, the enolates derived from α,α‐dibromoketones react with the α,β‐unsaturated Fischer alkoxycarbene complexes to obtain tetrasubstituted cyclopropanes, which are then treated with ceric‐ammonium nitrate to yield the final products. The methodology tolerates diverse functional groups, and high diastereoselectivity (dr ≥ 98:2) is observed in all cases. [ABSTRACT FROM AUTHOR]

The silaboration of [1.1.1]propellane enables direct introduction of B and Si functional groups onto the bicyclo[1.1.1]pentane (BCP) scaffold in high yield under mild, additive‐free conditions. The silaborated BCP can be obtained on a gram‐scale in a single step without the need for column‐chromatographic purification, and is storable and easy to handle, providing a versatile synthetic intermediate for BCP derivatives. We also describe various conversions of the C−B/C−Si bonds on the BCP scaffold, including development of a modified Suzuki–Miyaura cross‐coupling reaction at the highly sterically hindered bridgehead sp3 carbon center of the BCP skeleton using a combination of highly activated BCP boronic esters, copper(I) oxide, and a PdCl2(dppf) catalyst system. [ABSTRACT FROM AUTHOR]

A method for the double functionalization of graphene oxide (GO) under mild alkaline conditions has been developed. Two functional groups were covalently linked to GO in two steps: the first group was attached by an epoxide ring‐opening reaction and the second, bearing an amine function, was covalently conjugated to benzoquinone attached to the GO. The doubly functionalized GO was characterized by several techniques, confirming the sequential covalent modification of the GO surface with two different functional groups. This method is straightforward and the reaction conditions are mild, allowing preservation of the structure and properties of GO. This strategy could be exploited to prepare multifunctional GO conjugates with potential applications in many fields ranging from materials science to biomedicine. [ABSTRACT FROM AUTHOR]

We provide a seminal example of the utility of the 1,2‐azaborine motif as a 4C+1N+1B synthon in organic synthesis. Specifically, conditions for the practically scalable photoisomerization of 1,2‐azaborine in a flow reactor are reported that furnish aminoborylated cyclobutane derivatives. The C−B bonds could also be functionalized to furnish a diverse set of highly substituted cyclobutanes. [ABSTRACT FROM AUTHOR]

A synthesis of highly substituted 2,4‐diacylpyrroles through a Cu‐catalyzed dimerization of acylazirines generated in situ by a photochemical valence isomerization is described. The shown methodology allows the use of simple precursors and a readily available copper(II)‐catalyst. Since the reaction is best performed at elevated temperatures, a method to adjust the temperature of the reaction mixture during this dual light and metal‐induced process was established. Additionally, mechanistic studies of the reaction were performed in order to provide a deeper understanding of the chemistry of 2‐acylazirines. [ABSTRACT FROM AUTHOR]

The influence of substituents on α‐borylated phosphorus ylides (α‐BCPs) has been investigated in a combined experimental and quantum chemical approach. The synthesis and characterization of Me3PC(H)B(iBu)2 (1), consisting of small Me substituents on phosphorous and iBu residues on boron, is reported. Compound 1 is accessible through a novel synthetic approach, which has been further elucidated through DFT studies. The reactivity of 1 towards various small molecules was probed and compared with that of a previously published derivative, Ph3PC(Me)BEt2 (2). Both α‐BCPs react with NH3 to undergo heterolytic N−H bond cleavage. Different di‐ and trimeric ring structures were observed in the reaction products of 1 with CO and CO2. With PhNCO and PHNCS, the expected insertion products [Me3PC(H)(PhNCO)B(iBu)2] and [Me3PC(H)(PhNCS)B(iBu)2], respectively, were isolated. [ABSTRACT FROM AUTHOR]

Although various functionalized units can be incorporated into polyolefins by transition metal catalyzed coordination copolymerizations of nonfunctionalized olefins with polar functional monomers, the incorporated functional units are largely limited to a C1 unit from either CO or C2 units from vinyl monomers. Reported here is the Pd‐catalyzed copolymerization of ethylene with cyclopropenone, leading to incorporation of C3 units with functional groups, α,β‐unsaturated ketones, in the chain. Coordination‐insertion of the carbonyl group and ring opening of the strained three‐membered ring are proposed as the key steps in the mechanism. Under different reaction conditions an isolated ketone structure was afforded as the major carbonyl unit, and could be generated by the copolymerization of ethylene with CO formed in situ from cyclopropenone. [ABSTRACT FROM AUTHOR]

Substituted pyrazolines were obtained by Ni(ClO4)2·6H2O‐catalyzed reaction of 1,5‐diazabicyclo[3.1.0]hexanes with donor‐acceptor cyclopropanes. The mechanism of this reaction includes alkylation of diaziridine nitrogen with Lewis acid‐activated donor‐acceptor cyclopropane followed by hydration of the formed 1,6‐zwitterionic intermediate and oxidation of pyrazolidine with air oxygen. This pathway is realized when starting bicyclic diaziridines have bulky alkyl substituent(s) at the C(6) atom preventing (3+3)‐annulation of two three‐membered rings. [ABSTRACT FROM AUTHOR]

An unprecedented Michael/intramolecular etherification cascade reaction of phenyl vinyl selenone with 3‐hydroxyoxindoles under aqueous basic conditions at room temperature is described. The method provides a domino access to new spirooxindole 2,2‐disubstituted oxetanes in moderate to good yields under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Herein, a full structural description is presented for the archetypical supramolecular synthone squaric acid (3,4‐dihydroxy‐3‐cyclobutene‐1,2‐dione), placed in the gas phase by laser ablation and characterized by chirped pulse Fourier transform microwave technique. Free from natural environmental disturbances, two different anti‐anti and syn‐anti planar forms and the corresponding water clusters have been revealed in a supersonic expansion. The substitution structure of the most stable anti‐anti conformer has also been extracted from the analysis of the rotational spectra of the 13C and 18O isotopic species in their natural abundance. The interplay between inter‐ and intramolecular interactions involving hydroxy and carbonyl groups has been analyzed by QTAIM (quantum theory of atoms in molecules) methods for squaric acid and its water clusters to understand their chemical behavior and further rationalize their role in the stabilization of these molecular systems. [ABSTRACT FROM AUTHOR]

Catalytic diastereo‐ and enantioselective hydroalkenylation of 3,3‐disubstituted cyclopropenes with readily accessible alkenylboronic acids, promoted by a chiral phosphine/Co complex, is presented. Such a process constitutes the unprecedented and direct introduction of a wide range of alkenyl groups onto the cyclopropane motif to afford multisubstituted cyclopropanes in up to 95 % yield with greater than 95:5 d.r. and 99:1 e.r. Functionalization of the products delivered enantioenriched cyclopropanes that are otherwise difficult to access. [ABSTRACT FROM AUTHOR]

A catalytic nucleophilic addition reaction of 3‐hydroxybenzofuran‐2‐carboxylic acid derivatives to 2H‐azirines for the high‐yield synthesis of NH‐aziridines with a 3‐coumaranone substituent has been developed. The Ph3PAuNTf2‐catalyzed reaction is diastereoselective to give predominantly (RS,SR)‐isomer of aziridine in good yield. The Ni(hfacac)2‐catalyzed reaction affords aziridines in up to 98% yield and low or moderate diastereoselectivity, which in some cases is opposite to that observed for the gold(I)‐catalyzed reaction. The Ph3PAuNTf2 works well for sterically hindered azirines as well as benzofurans bearing electron‐withdrawing groups, whereas Ni(hfacac)2 is the catalyst of choice for the preparation of aziridines having diazoacetyl substituent. The latter compounds can serve as substrates for the synthesis of fused aziridines via Buchner ring expansion reaction. [ABSTRACT FROM AUTHOR]

Cycloaddition reactions can be used to efficiently assemble pyrrolidine rings that are significant in a variety of chemical and biological applications. We have developed a method for the formal cycloaddition of cyclopropyl ketones with hydrazones that utilizes photoredox catalysis to enable the synthesis of a range of structurally diverse pyrrolidine rings. The key insight enabling the scope of photoredox [3+2] cycloadditions to be expanded to C=N electrophiles was the use of a redox auxiliary strategy that allowed for photoreductive activation of the cyclopropyl ketone without the need for an exogenous tertiary amine co‐reductant. These conditions prevent the deleterious reductive ring‐opening of the cyclopropyl substrates, enabling a range of less‐reactive coupling partners to participate in this cycloaddition. [ABSTRACT FROM AUTHOR]

A regioselective synthesis of general applicability has been designed for the one‐pot preparation of 2,3‐disubstituted‐cyclobutenones from iodoalkynes through cyclobutenylation, Suzuki CC coupling, and ketone formation. This one‐pot methodology has been applied to the selective synthesis of an orally active cyclooxygenase II inhibitor. Furthermore, the obtained cyclobut‐2‐en‐1‐ones were used as synthons in several transformations, such as, the preparation of β‐lactams, phthalazines, cyclohexa‐2,5‐dien‐1‐ones, and cyclopent‐3‐en‐1‐ones. [ABSTRACT FROM AUTHOR]

3‐Allyl‐substituted quinolones undergo a triplet‐sensitized di‐π‐methane rearrangement reaction to the corresponding 3‐cyclopropylquinolones upon irradiation with visible light (λ=420 nm). A chiral hydrogen‐bonding sensitizer (10 mol %) was shown to promote the reaction enantioselectively (88–96 % yield, 32–55 % ee). Surprisingly, it was found that the enantiodifferentiation does not occur at the state of initial product formation but that it is the result of a deracemization event. The individual parameters that control the distribution of enantiomers in the photostationary state have been identified. Mirror mirror on the wall, where has the other enantiomer gone? Catalyst 2 establishes an equilibrium between the two enantiomers 1 and ent‐1 in which one enantiomer prevails (up to 55 % ee). The deracemization is responsible for the enantioselective formation of 3‐cyclopropylquinolones from 3‐allyl‐substituted quinolones. [ABSTRACT FROM AUTHOR]

[Display omitted] • Protic ionic liquid (PIL) was used simultaneously as solvent, catalyst, nucleophile. • Switching chemoselectivity by changing PIL has been demonstrated for the first time. • Donor-acceptor cyclopropanes were transformed to new ring systems by domino reactions. • Unusual spiro[2-thioxopyrrolidine-3,2′-indane-1′,3′-diones] were formed via N -attack. • Unprecedented ring system of thieno[2,3-c][2]benzazepine was obtained via S -attack. Triple-role thiocyanate-containing protic ionic liquids (PILs) were employed as a regenerable solvent, a Brønsted acid catalyst, and a source of the nucleophile for the ring-opening of 1,3-indanedione-based donor–acceptor cyclopropanes. [ABSTRACT FROM AUTHOR]

Palladium‐ and rhodium‐catalyzed selective reactions of 2H‐azirines and N‐(acyloxy)amides leading to α‐amino oxime esters were described. The regioselectivities of the reactions are catalyst‐controlled, and two different α‐amino oxime esters were selectively obtained in high yields. These reactions involved the construction of new N–O and C–N bonds, which are characterized by 100 % atom economy, good to excellent yields, and mild reaction conditions. Palladium‐ and rhodium‐catalyzed selective reactions of 2H‐azirines and N‐(acyloxy)amides leading to α‐amino oxime esters were described. The regioselectivity is catalyst‐controlled, and two different α‐amino oxime esters were chemoselectively obtained in high yields. [ABSTRACT FROM AUTHOR]

The concept and the first example for electronic frustration within a C−B π‐bond arising from the competition for a lone pair of electrons is reported. The α‐borylated phosphorus ylide (α‐BCP) Ph3PC(CH3)BEt2 (1) has been synthesized, characterized, and investigated with the aid of density functional theory calculations. These show the presence of a highly polarized C−B π‐bond, induced by the electron‐withdrawing Ph3P+ substituent. This competition for the C‐based lone pair of electrons leads to an FLP‐type reactivity (FLP=frustrated Lewis pair), which has been demonstrated by reacting 1 with various small molecules: the dimeric insertion products [Ph3PC(CH3)COBEt2]2 (2) and [Ph3PC(CH3)(CO2)BEt2]2 (5) result from the reaction of 1 with CO and CO2, respectively, whereas monomeric products of the general formula [Ph3PC(CH3)(XYZ)BEt2] were obtained by treating 1 with COS (3), CS2 (4) or the heterocumulenes PhNCO (6) and PhNCS (7). A strained C−B π‐bond: The concept and the first example for electronic frustration within a C−B π‐bond arising from the competition for a lone pair of electrons is reported. The α‐borylated phosphorus ylide (α‐BCP) Ph3PC(CH3)BEt2 (1) has been synthesized, characterized, and investigated with the aid of density functional theory calculations. 1 has been demonstrated to react with various small molecules. [ABSTRACT FROM AUTHOR]

Abstract: Treatment of epoxides with bis(trimethylsilyl)‐selenide under strictly controlled conditions allows to isolate β‐hydroxy selenols which evidence an unexpected stability, taking into account their known propensity to afford diselenides. Also thiiranes and aziridines lead to functionalized selenols bearing a thiol and a N‐Ts‐ or N‐Boc‐protected amino moiety on β‐position. These selenols were stable enough to react with different electrophiles. Ab‐initio DF calculations on two suitable model systems, n‐propyl selenol and β‐hydroxy derivative, allow to ascribe the observed low tendency to oxidation to noncovalent interactions between the selenol moiety and the −OH group. [ABSTRACT FROM AUTHOR]

Fluorinated α‐bromoenones react readily with amino alcohols containing a secondary amino group to give monocyclic morpholine derivatives or unexpected bicyclic compounds containing a morpholine moiety fused with an oxetane ring. The reactions are highly stereoselective. The assembly of these heterocycles starts with an aza‐Michael addition followed by intermolecular substitution and addition processes. [ABSTRACT FROM AUTHOR]

Abstract: The first example of (3+3)‐annulation of two different three‐membered rings is reported herein. Donor‐acceptor cyclopropanes in reaction with diaziridines were found to afford perhydropyridazine derivatives in high yields and diastereoselectivity under mild Lewis acid catalysis. The disclosed reaction is applicable for the broad substrate scope and exhibits an excellent functional group tolerance. [ABSTRACT FROM AUTHOR]

Several varieties of cycloaddition as well as nucleophilic and free radical addition to the highly reactive central bond of the title fluorocarbon (1) are described. [2 + 2] Cycloaddition to 1 has made available four of the five known representatives of the [2.2.2]propellane ring system, which are rare because of their extreme strain (in the absence of fluorine substitution) and high reactivity. Two of these, a propellanone and a propellene, are first reported here. Quantum mechanical calculations have shed light on many of these transformations. [ABSTRACT FROM AUTHOR]

A 4‐methylene‐5‐spirocyclopropane isoxazolidine was prepared with complete regioselectivity through the 1,3‐dipolar cycloaddition reaction of a pyrroline N‐oxide with a cyclopropylidene acetate, followed by reduction and elimination. Thermal rearrangement of the isoxazolidine gives an indolizidinone that retains the exocyclic methylene moiety. The exo‐methylene substituent confers a particular reactivity to this heterocycle; it can undergo thermal hetero‐Diels–Alder cycloadditions and ene reactions with different reaction partners. [ABSTRACT FROM AUTHOR]