Synthesis of 2,4,6,8,9,11-hexaaza[3.3.3]propellanes as a new molecular skeleton for explosives

Azapropellanes are of great interest in many disciplines, including materials science and medicinal chemistry. Various synthetic approaches for azapropellanes have been explored; however, the synthetic study of the polyazapropellane skeleton containing five or more nitrogen atoms is rare. Here, we report a simple yet highly efficient protocol for the synthesis of the hexaaza[3.3.3]propellane skeleton as a building block for high energy materials for the first time. The key reactions include the Boc₂O-assisted cyclization of glycoluril diamine without a column purification step and the first full reduction of all the three carbonyl groups to the methylene groups through a combination of LiAlH₄ and DIBAL-H. All the structures were confirmed by spectroscopic and X-ray analyses.     

Propellanes. Part LXXVIII. Preparation of Several Triaza[3.3.3]propellanes and an Oxadiaza[3.3.3]propellane

3,7,10-Tribenzyl-3,7,10-triaza[3.3.3]propellane ( 4a ), 3,7-dibenzyl-10-phenyl-3,7,10-triaza[3.3.3]propellane ( 4c ), 3,7-dibenzyl-10-(p-tolyl)-3,7,10-triaza[3.3.3]propellane ( 4b ), and 3-oxa-7,10-diaza[3.3.3]propellane ( 6 ) have been prepared.     

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.     

Wagner-Meerwein rearrangement of a [3.3.3]- to a [4.3.3]propellane: deuterium tracer and conformational analysis

Formation of (-)-[4.3.3]propellane 4 from (-)-14-hydroxymodhephene (2) proceeds through a Wagner-Meerwein rearrangement via C3--C4 bond-shift to give a stable intermediate, dimethylcyclohexadienyl cation A, which undergoes deprotonation. Herein, this mechanism was investigated by using a deuterium labeled substrate at the C-14 methylene group of (-)-2, which was incorporated into the C-4 position of (-)-[4.3.3]propellane 4. The stereostructure of (-)-4 was investigated by applying a combination of NMR experimental and theoretical approaches.     

Reduction studies on benzaza[3.3.3]propellanc derivatives

Sodium borohydride reduction of 3-methyl-2,3-dioxo-7,8-benzo-3-aza[3.3.3]propellan-6-one (1b) gave 2,4-dioxo-3-methyl-7,8-benzo-3-aza[3.3.3]propellan-6-ol, while lithium aluminum hydride reduction gave 3-methyl-7,8-benzo-3-aza[3.3.3]propellan-6-ol, which on oxidation, gave the corresponding ketone. This ketone formed the corresponding thioketal upon reaction with 1,2-ethanedithiol. Raney nickel desulfurization of the thioketal provided 3-methyl-6,7-benzo-3-aza[3.3.3]propellane. The same compound was also obtained in poor yield by forming the thioketal of Ib followed by lithium aluminum hydride reduction and Raney nickel desulfurization of the product. Desulfurization of the thioketal of Ib gave 2,4-dioxo-6,7-Benzo-3-aza[3.3.3]propellane.     

An Improved Synthesis of Bicyclo[3.3.3]undecane

A shorter and significantly higher-yield procedure for the preparation of bicyclo[3.3.3]undecane (manxane) is reported.     

异色满并[4,3-b]喹啉衍生物的合成

早在1931年,Hetherington等从念珠状曲菌(Aspergillus Cand inin)和土曲菌(Asperillus tereus)等菌类中分离出带有异色满(Isochroman)环系结构的左旋抗菌素橘霉素(C itrinin),后来又相继发现诸多带有异色满环系的天然产物[1-3],新近在软木木质素中也发现了多种具有异色满结构的     

Chemo- and diastereoselective synthesis of new oxa[3.3.3]propellane via a domino cascade four-component reaction based on diketene

A highly convergent, eco-friendly and straightforward synthesis of new O-fused heterocycles, functionalized indeno[1,2-b]furan derivatives was successfully accomplished through a one-pot four-component cascade reaction involving, ninhydrin, malononitrile, diketene and various primary amines in the presence of a catalytic quantity of triethylamine in ethanol at ambient temperature, in one pot fashion. This new efficient cascade reaction generates two rings by the simultaneous construction of C-N (one), C-O (two) and C-C (two) multiple bonds, presumably through a sequence of Knoevenagel reaction/Michael addition/intramolecular O-cyclization and imine-enamine/keto-enol tautomerization. The merits of this protocol are highlighted as utilization of inexpensive commercially accessible starting materials, operational simplicity, atom economy, clean reaction profile, simple work-up procedure being conducted at ambient temperature in relatively short reaction times, preventing chromatographic purification, giving excellent yields, and tolerance to a wide variety of functional groups.     

Synthesis of heterocyclic [3.3.3]propellanes via a sequential four-component reaction

A highly chemoselective heteroannulation protocol for the synthesis of unreported polysubstituted heterocyclic [3.3.3]propellanes has been developed by sequential four-component reaction of ninhydrin, malononitrile, primary amines, and dialkyl acetylenedicarboxylates under mild conditions in water. To the best of our knowledge, there are no previous reports for the synthesis of these classes of heterocyclic [3.3.3]propellanes. The merit of this sequential Knoevenagel condensation/enamine formation/Michael addition/cyclization sequence is highlighted by its high atom-economy, excellent yields, the use of water as reaction media, and the efficiency of production without the use of any activator or metal promoters. This synthesis serves as a nice addition to group-assistant-purification (GAP) chemistry in which purification via chromatography and recrystallization can be avoided, and the pure products were obtained simply by washing the crude products with 95% ethanol.     

Synthesis of novel dihydrothiazolo[3,2-a]pyrimidinone derivatives

Condensation of 2-amino-4-hydroxy-2-mercaptopyrimidine (2) hydrate and ethyl 4-bromocrotonate gave a mixture of ethyl 7-amino-2,3-dihydro-5-oxo-5H-thiazolo[3,2-a]pyrimidine-3-acetate (4) and 2a,3-dihydro-1-thia-5,8,8b-triazaacenaphthylene-4,7(2H)-dione (5) whereas reaction of 2 with 4-bromocrotononitrile afforded only 7-amino-2,3-dihydro-5-oxo-5H-thiazolo[3,2-a] pyrimidine-3-acetonitrile. Reaction of the tricycle 5 (which was isolated as a hemihydrate) with excess methyl iodide/potassium carbonate in dimethylformamide resulted in both ring hydrolysis and methylation to give 3,4-dihydro-1,7-dimethyl-4- [(methylthio)methyl]-2H-pyrimido[1,6-a]pyrimidine-2,6,8(1H,7H)-trione (10). Methylating 5 with excess methyl iodide/sodium methoxide in methanol also resulted in ring fragmentation and methylation but instead afforded methyl 7-methyl-amino-2,3-dihydro-5-oxo-7H-thiazolo[3,2-a]pyrimidine-3-acetate. The mechanistic aspects of these reactions are discussed.     

Synthesis of novel spiro-cyclohexene bicyclo[2.2.2]octane derivatives

A methodology for the synthesis of novel spiro-cyclohexene bicyclo[2.2.2]octane derivatives, including Claisen rearrangement and ring-closing metathesis (RCM) as key synthetic steps, is described.     

Attempted synthesis of a substituted [2.2.2]propellane derivative from triptycene derivatives

Bromotriptycene derivatives substituted at the bridgehead were subjected to varying reaction conditions in the attempt to obtain a substituted [2.2.2]propellane. The desired cyclization was not effected. The bromine atoms were replaced by hydrogens.     

Synthesis and characterization of novel calix[6]phyrin derivatives

Three novel calix[6]phyrin derivatives have been synthesized by reaction of corresponding tripyrrane with aromatic aldehyde. The reaction condition was optimized and the structures of these compounds have been characterized by NMR and MS.     

Synthesis of pyrazolo[3,4-c]isoquinoline and pyrazolo[3,4-b]pyridine derivatives from azomethines and CH-acidic compounds

Summary Donor substituted arylidene aminopyrazoles1a–c and CH-acidic 1,3-dicarbonyl compounds2a–e give in ethanol in an addition/cyclization reaction pyrazolo[3,4-c]isoquinolines4a–i and pyrazolo[3,4-b]pyridine derivatives5a,b, respectively. Using ethyl cyanoacetate as CH-acidic component, cinnamate6 and the cyano substituted pyrazolo[3,4-b]pyridine7 are formed.

---

Synthese von Pyrazolo[3,4-c]isochinolin- und Pyrazolo[3,4-b]pyridin-Derivaten aus Azomethinen und CH-aciden Verbindungen

Zusammenfassung Die Reaktion der donorsubstituierten Aryliden-aminopyrazole1a–c mit den CH-aciden 1,3-Dicarbonylverbindungen2a–e führt in einer Additions/Cyclisierungsreaktion zu den Pyrazolo[3,4-c]isochinolin-4a–i bzw. Pyrazolo[3,4-b]pyridin-Derivaten5a,b. Verwendet man Cyanessigester als CH-acide Komponente, werden der Zimtsäureester6 und das cyanosubstituierte Pyrazolo[3,4-b]pyridin7 gebildet.

     

Highly stereocontrolled synthesis of [3.3.3] propellane sesquiterpenes. ( ± )-Modhephene and (±)-epimodhephene

Stereospecific total synthesis of (±)-modhephene (2) and (±)-epimodhephene (3) are reported. Conjugate addition of 1-trimethylsilyl-1-butyn-4-yl cuprate (BF₃-etherate catalysis) to bicyclic ketone 6, fluoride ion-promoted deblocking of the terminal acetylene, and ene reaction, gave tricyclic enone 11. Sequential Wittig methylenation, regiocontrolled epoxidation, and Lewis acid catalyzed isomerization afforded ketone 14 whose double bond relocation and Wolff-Kishner reduction led exclusively to 2. In a still shorter route to 3, 3-butenyl cuprate addition to 6 was utilized to gain access to 7. Thermolysis of this intermediate, methylenation, and double bond isomerization were found to deliver pure 3 successfully.     

Synthesis and phototransformations of novel styryl-substituted furo-benzobicyclo[3.2.1]octadiene derivatives

Novel cis- and trans-(o-H/Me/vinyl) substituted styryl furo-benzobicyclo[3.2.1]octadiene derivatives (7a,b, 8) were prepared and transformed to the novel naphthofuran derivatives of benzobicyclo[3.2.1]octadiene (6a,b) and novel phenanthrene-benzobicyclo[3.2.1]octadiene derivative (11) by photochemical electrocyclic ring closure in the presence of iodine and by intramolecular photoinduced [4+2] cycloaddition, respectively. These novel annelated bicyclo[3.2.1]octadiene derivatives (6a,b, 11) are especially interesting for their rigid methano-bridged junction of two aromatic units at defined geometrical arrangement and thereby as potentials for molecular clips.     

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.