Sodium Bicyclo[1.1.1]pentanesulfinate: A Bench-Stable Precursor for Bicyclo[1.1.1]pentylsulfones and Bicyclo- [1.1.1]pentanesulfonamides

Herein, we present the synthesis of the bench-stable sodium bicyclo[1.1.1]pentanesulfinate (BCP-SO₂Na) and its application in the synthesis of bicyclo[1.1.1]pentyl (BCP) sulfones and sulfonamides. The salt can be obtained in a four-step procedure from commercially available precursors in multigram scale without the need for column chromatography or crystallization. Sulfinates are known to be useful precursors in radical and nucleophilic reactions and are widely used in medicinal chemistry. This building block enables access to BCP sulfones and sulfonamides avoiding the volatile [1.1.1]propellane which is favorable for the extension of SAR studies. Further, BCP-SO₂Na enables the synthesis of products that were not available with previous methods. A chlorination of BCP-SO₂Na and subsequent reaction with a Grignard reagent provides a new route to BCP sulfoxides. Several products were analyzed by single-crystal X-ray diffraction.     

Si3S-, Si3Se-, Si3Te-Bicyclo[1.1.0]butanes and Si3S2-Bicyclo[1.1.1]pentane

The reaction of trisilirene 1 with propylene sulfide or elemental sulfur produced Si₃S-bicyclo[1.1.0]butane 2, which underwent Si–Si insertion of a second S atom forming Si₃S₂-bicyclo[1.1.1]pentane 3. Analogous reactions of 1 with elemental Se or Te resulted in the formation of heavier analogues of 2, namely, Si₃Se-bicyclo[1.1.0]butane 4 and Si₃Te-bicyclo[1.1.0]butane 5.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

GRAPHICAL ABSTRACT     

Thermal behaviour of some dibenzobicyclo[2.2.2]octane derivatives

A number of dibenzobicyclo[2.2.2]octane derivatives have been studied due to the interest of such compounds as ligands for coordination compounds with potential biological activity. Their thermal behaviour has been analyzed in order to find out more information about their fragmentation. A connection between the bridge substituents and the fragmentation process has been observed.     

Synthesis of Bicyclo[1.1.1]pentane (BCP)-Based Straight-Shaped Diphosphine Ligands**

[1.1.1]Propellane, which is structurally simple and compact, exhibits promising potential for the synthesis of disubstituted straight-shaped bicyclo[1.1.1]pentane (BCP) compounds by manipulation of its highly reactive internal C−C bond. BCPs are considered to be isosteres of 1,4-disubstituted benzenes, which have found broad applications in the areas of functional molecules and drug discovery. The internal C−C single bond of [1.1.1]propellane is regarded as a charge-shift bond, which can be readily cleaved by radical means to construct BCPs. We herein report a novel synthetic method for (un)symmetric diphosphines based on the BCP motif, which can be interpreted as isosteres of 1,4-bis(diphenylphosphino)benzenes. The obtained BCP-diphosphine derivatives were used to generate a straight-shaped Au complex and an Eu-based coordination polymer.     

Bicyclo[1.1.1]pentane Embedded in Porphyrinoids**

We report a two-step approach to obtain synthetically versatile bicyclo[1.1.1]pentane (BCP) derivatives using Grignard reagents. This method allows the incorporation of BCP units in tetrapyrrolic macrocycles and the synthesis of a new class of calix[4]pyrrole analogues by replacing two bridging methylene groups with two BCP units. In addition, a doubly N-confused system was also formed in the presence of electron-withdrawing substituents at the BCP bridgeheads. The pyrrole rings in BCP containing macrocycles exist in 1,3-alternate or αβαβ conformations, as observed from single-crystal X-ray diffraction analyses and 2D NMR spectroscopy.     

Synthesis and characterization of poly(benzazoles) containing the bicyclo[2.2.2]octane moiety

Poly(benzobisoxazoles) (PBOs), poly(benzobisthiazoles) (PBTs) and copolymers thereof containing the 2,5-dihydroxybicyclo[2.2.2]octane moiety have been prepared and studied. The homopolymers were synthesized by the polycondensation of 2,5-dihydroxybicyclo[2.2.2]octane-1,4-dicarboxylic acid with 4,6-diamino-1,3-benzenediol dihydrochloride or 2,5-diamino-1,4-benzenedithiol dihydrochloride in poly(phosphoric acid). Random and block copolymers (PBO–PBT) were also prepared. The polymers were characterized by solubility, X-ray diffraction, spectroscopy (infrared and solid-state ¹³C nuclear magnetic resonance), and thermal analysis such as differential scanning calorimetry and thermogravimetric analysis. Thermogravimetric analysis showed thermal stability of the polymers above 375°C in air and under argon atmosphere. The polymers exhibited high resistance to organic and inorganic solvents. The polymers were converted to the more stable aromatic polymers via dehydration and retro Diels–Alder reactions of the 2,5-dihydroxybicyclo[2.2.2]octyl moiety by pyrolysis. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 277–281, 1998     

Synthesis,characterization, and properties of colorless rigid-rod poly(benzobisthiazole) derived from bicyclo[2.2.2]octane

Polycondensation in polyphosphoric acid of 2,5-diamino-1,4-benzene dithiol dihydrochloride with bicyclo[2.2.2]octane-1,4-dicarboxylic acid, as well as the corresponding dimethyl ester or diacid chloride, led to rigid-rod benzobisthiazole polymers. Colorless and soluble polymers with intrinsic viscosities as high as 30.6 dL/g (methanesulfonic acid, 30°C) were obtained. The ultraviolet-visible spectrum of a polymer film cast from methanesulfonic acid under reduced pressure displayed no absorptions in the visible range (400–900 °m). The polymer was thermooxidatively stable up to 420°C in air as determined by thermogravimetric analysis. Fibers spun from a lyotropic polyphosphoric acid solution exhibited a tensile strength of 300–450 Ksi, a modulus of 26 Msi, and a compressive strength of 53 Ksi. Wide-angle X-ray scattering patterns of polymer fibers indicated a 3-dimensional crystal structure rather than a nematic liquid crystal structure. © 1994 John Wiley & Sons, Inc.     

1,4-二氮杂双环[2.2.2]辛烷催化的有机化学反应

综述了有机小分子催化剂1,4-二氮杂双环[2.2.2]辛烷(DABCO)在有机合成反应中的应用与发展。这种有机小分子催化的反应大多数条件温和、操作简单;相对过渡金属而言,对环境友好;在一定条件下,这种催化剂可以回收再利用。     

1,3-Difunctionalizations of [1.1.1]Propellane via 1,2-Metallate Rearrangements of Boronate Complexes

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.     

9,9-Dimethyl-8,10-dioxapentacyclo[5.3.0.0.0.0]decane and naphthotetracyclo[5.1.0.0.0]oct-3-ene: new substituted [1.1.1]propellanes as precursors to 1,2,3,4-tetrafunctionalized bicyclo[1.1.1]pentanes

Two new substituted [1.1.1]propellanes have been generated from the corresponding bicyclo[1.1.0]butanes in either single-step (1a) or four-step procedures (1b). The observed degree of double lithiation of the bicyclo[1.1.0]butanes is discussed in the context of DFT computational results. Addition reactions across the central C(1)-C(3) bonds of the propellanes were studied. Only the propellane 1b gave the biacetyl addition product.     

1,3-bicyclo[1.1.1]pentanediyl: the shortest rigid linear connector of phenylated photochromic units and a 1,5-dimethoxy-9,10-di(phenylethynyl)anthracene fluorophore

An excess of bis-1,3-(4-iodophenyl)bicyclo[1.1.1]pentane, prepared in 63 % yield by iodination of 1,3-diphenylbicyclo[1.1.1]pentane, was selectively mono-coupled with 9-ethynyl-1,5-dimethoxy-10-phenylethynylanthracene (26), and subsequently with the zinc derivatives of 1-(2-methyl/methoxy-4-methyl-5-phenylthiophen-3-yl)-2-(2-methyl/methoxy-4-methylthiophen-3-yl)perfluorocyclopentenes (38-H-41-H). Regioselective synthesis of the 2-unsubstituted thiophenes 38-H-41-H required intermediate preparation of 2-trimethylsilyl-3,5-dimethyl-4-bromothiophene (37) or 2-trimethylsilyl-5-methoxy-3-methyl-4-bromothiophene (40). Protection of the alpha-position of the thiophene ring with a 2-trimethylsilyl group blocks the rearrangement of the 4-lithio derivatives into the corresponding 2-lithiated thiophenes. With the bicyclo[1.1.1]pentane fragment linking the photochromic units 1-3 and 1,5-dimethoxy-9,10-di(phenylethynyl)anthracene as a fluorescent part, quantitative resonance energy transfer between the excited state of the fluorophore (donor) and the closed form of the photochromic units 1-3 (acceptors) was observed. The closed forms of the methoxy-substituted photochromic units 2 and 3 are less resistant to UV light (313 nm) than the closed form of 1.     

1-氮杂环[2.2.2]辛烷的高效合成

将4-（2-羟乙基）哌啶蒸汽在425 ℃下通过CNM-3型固体酸催化剂进行分子内脱水反应,一步合成了目的产物1-氮杂环[2.2.2]辛烷（奎宁环）,4 h内25 g 4-（2-羟乙基）哌啶蒸汽单程收率可达76.8%,最高收率84.3%。 该方法原料易得,适合于奎宁环的工业化制备。     

Organic reactions catalyzed by 1, 4-diazabicyclo [2.2.2] octane (DABCO)

The organic reactions catalyzed by 1, 4-diazabicyclo [2.2.2] octane (DABCO) are reviewed. Most of the reactions start conveniently from available substrate and proceed under mild conditions. The reactions are environmentally friendly and the catalyst can be recycled in some cases. The perspectives on DABCO-catalyzed reactions are pointed out. __________ Translated from Chemistry online, 2007, 70(10): 759–765 [译自: 化学通报]     

Recent advances in the applications of [1.1.1]propellane in organic synthesis

As a highly strained small molecule, [1.1.1]propellane has been widely used in various synthetic transformations owing to the exceptional reactivity of the central bond between the two bridgehead carbons. Utilizing strain-release approaches, the rapid development of strategies for the construction of bicyclo[1.1.1]pentane (BCP) and cyclobutane derivatives using [1.1.1]propellane as the starting material has been witnessed in the past few years. In this review, we highlight the most recent advances in this field. Accordingly, the reactivity of [1.1.1]propellane can be divided into three pathways, including radical, anionic and transition metal-catalyzed pathways under appropriate conditions.     

Recent advances in the applications of [1.1.1]propellane in organic synthesis

As a highly strained small molecule, [1.1.1]propellane has been widely used in various synthetic transformations owing to the exceptional reactivity of the central bond between the two bridgehead carbons. Utilizing strain-release approaches, the rapid development of strategies for the construction of bicyclo[1.1.1]pentane (BCP) and cyclobutane derivatives using [1.1.1]propellane as the starting material has been witnessed in the past few years. In this review, we highlight the most recent advances in this field. Accordingly, the reactivity of [1.1.1]propellane can be divided into three pathways, including radical, anionic and transition metal-catalyzed pathways under appropriate conditions.     

A General and Practical Route to Functionalized Bicyclo[1.1.1]Pentane-Heteroaryls Enabled by Photocatalytic Multicomponent Heteroarylation of [1.1.1]Propellane

1-Aryl-substituted bicyclo[1.1.1]pentanes (BCPs) are an important class of BCP derivatives with widespread application in drug development. Most syntheses of these materials require multiple chemical steps via BCP electrophiles or nucleophiles derived from [1.1.1]propellane. Although one-step, multicomponent radical cross-coupling reactions could provide a more sustainable and rapid route to access diverse heteroarylated BCPs, current approaches are limited to tertiary alkyl radicals, leading to a decrease in their practical value. In this study, a conceptually different approach enabled by a radical multicomponent heteroarylation of [1.1.1]propellane to access functionalized heteroarylated BCPs is described. Importantly, this protocol is compatible with primary-, secondary-, and tertiary aliphatic radicals, as well as various fluoroalkyl radical sources, thus enabling rapid library generation of sought-after BCP derivatives for drug development.     

1,3‐Difunctionalizations of [1.1.1]Propellane via 1,2‐Metallate Rearrangements of Boronate Complexes

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.     

Studies on photochemical rearrangement of non-oxygenated bicyclo[2.2.2]octenones and mono-oxygenated bicyclo[2.2.2]octenones from masked o-benzoquinones: Access to protoilludane and marasmane skeletons

In this work, we described flexible approaches to protoilludane-like (5,6,4-tricyclic ring) and marasmane-like (5,6,3-tricyclic ring) skeletons with naturally occurring cis/anti/cis stereochemistry using photochemical rearrangement of bicyclo[2.2.2]octenones and Diels-Alder reaction of masked o-benzoquinones as the key steps.     

Synthesis of molecular motors incorporating para-phenylene-conjugated or bicyclo[2.2.2]octane-insulated electroactive groups

The insulating role of the bicyclo[2.2.2]octane fragment has been theoretically evaluated by comparing the electronic coupling parameter (V(ab)) in 1,4-bis(ferrocenyl)benzene (1) and 1,4-bis(ferrocenyl)bicyclo[2.2.2]octane (2). The geometries were optimized by DFT and an extended Hückel calculation was performed to evaluate V(ab) by the dimer splitting method. The calculations showed a 12-fold decrease of the electronic coupling from 60 meV for 1 to 5 meV for 2. The second part describes the synthesis of two potential molecular motors with one incorporating the insulating bicyclo[2.2.2]octane fragment. These molecules are based on a ruthenium complex bearing a tripodal stator functionalized to be anchored onto surfaces. The ferrocenyl electroactive groups and the cyclopentadienyl (Cp) rotor are connected through a p-phenylene spacer (5) or through a spacer incorporating an insulating bicyclo[2.2.2]octane moiety (6).     

Bridging and Conformational Control of Porphyrin Units through Non-Traditional Rigid Scaffolds

Connecting two porphyrin units in a rigid linear fashion, without any undesired electron delocalization or communication between the chromophores, remains a synthetic challenge. Herein, a broad library of functionally diverse multi-porphyrin arrays that incorporate the non-traditional rigid linker groups cubane and bicyclo[1.1.1]pentane (BCP) is described. A robust, reliable, and versatile synthetic procedure was employed to access porphyrin-cubane/BCP-porphyrin arrays, representing the largest non-polymeric structures available for cubane/BCP derivatives. These reactions demonstrate considerable substrate scope, from utilization of small phenyl moieties to large porphyrin rings, with varying lengths and different angles. To control conformational flexibility, amide bonds were introduced between the bridgehead carbon of BCP/cubane and the porphyrin rings. Through varying the orientation of the substituents around the amide bond of cubane/BCP, different intermolecular interactions were identified through single crystal X-ray analysis. These studies revealed non-covalent interactions that are the first-of-their-kind including a unique iodine-oxygen interaction between cubane units. These supramolecular architectures indicate the possibility to mimic a protein structure due to the sp³ rigid scaffolds (BCP or cubane) that exhibit the essential conformational space for protein function while simultaneously providing amide bonds for molecular recognition.