Fragmentation‐Related Phosphonylation of Nucleophiles Utilizing P‐Alkyl 2,3‐oxaphosphabicyclo[2.2.2]octene 3‐oxide Precursors

New P‐alkyl 2,3‐oxaphosphabicyclo‐[2.2.2]octene 3‐oxides were synthesized by the Bayer–Villiger oxidation of the corresponding 7‐phosphanorbornene 7‐oxides and were used as precursors for reactive alkylmetaphosphonates useful in the phosphonylation of alcohols. This is the first case that the reactivity of the two regioisomers formed by O‐insertion was differentiated and that the fragmentation‐related phosphonylation leading to phosphonic acid‐esters was achieved under microwave‐assisted conditions.     

Synthesis and fragmentation of new 2‐phosphabicyclo[2.2.2]octene 2‐oxides

The substitution pattern of the 2‐phosphabicyclo[2.2.2]octene framework and the skeleton itself were varied to obtain new cycloadducts usable in phosphorylations and to study their ability to undergo fragmentation. Thus, an N‐methyl and several P‐trialkylphenyl derivatives ( 7 and 9 , respectively) were synthesized, together with two diaza species ( 8 ) whose stereostructure was evaluated by single crystal X‐ray analysis. Mechanistic studies on the UV light‐mediated photolysis of the P‐aryl phosphabicyclooctenes ( 9 ) in the presence of methanol supports the suggestion of a novel addition–elimination reaction path. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:626–632, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10052     

Steric Control in the π‐Dimerization of Oligothiophene Radical Cations Annelated with Bicyclo[2.2.2]octene Units

A Two series of oligothiophenes 2 (nT) (n=4,5), annelated with bicyclo[2.2.2]octene (BCO) units at both ends, and quaterthiophenes 3 a – c , annelated with various numbers of BCO units at different positions, were newly synthesized to investigate the driving forces of π‐dimerization and the structure–property relationships of the π‐dimers of oligothiophene radical cations. Their radical‐cation salts were prepared through chemical one‐electron oxidation by using nitrosonium hexafluoroantimonate. From variable‐temperature electron spin resonance and electronic absorption measurements, the π‐dimerization capability was found to vary among the members of the 2 (nT)^{+ .} SbF₆^? series and 3 ^{+ .} SbF₆^? series of compounds. To examine these results, density functional theory (DFT) calculations at the M06‐2X/6‐31G(d) level were conducted for the π‐dimers. This level of theory was found to successfully reproduce the previously reported X‐ray structure of ( 2 (3T))₂²⁺ having a bent π‐dimer structure with cis–cis conformations. The absorption bands obtained by time‐dependent DFT calculations for the π‐dimers were in reasonable agreement with the experimental spectra. The attractive and repulsive forces for the π‐dimerization were divided into four factors: 1) SOMO–SOMO interactions, 2) van der Waals forces, 3) solvation, and 4) Coulomb repulsion, and the effects of each factor on the structural differences and chain‐length dependence are discussed in detail.     

Regioselective synthesis and characterization of new 3‐aryl‐7‐trifluoromethyl‐[1,2,4]triazolo[4,3–a]pyrimidines

The regioselective synthesis and characterization of a new series of 3‐aryl‐7‐trifluoromethyl[1,2,4]triazolo[4,3–a]pyrimidines from the oxidative heterocyclization of 2‐(N′‐benzylidenehydrazino)‐4‐trifluoromethylpyrimidines with copper dichloride is described. J. Heterocyclic Chem., (2011).     

Stereoselectivity in the Diels‐Alder Cycloadditions of a Facially Dissymmetric Bicyclo[2.2.2]octadiene‐Grafted Maleic Anhydride with Exocyclic Butadienes. Unexpected Facial Selectivity in the Cycloaddition with 2,3,5,6‐tetramethylidenebicyclo[2.2.2]octene

The Diels‐Alder cycloadditions of facially dissymmetric maleic anhydride 1 with facially nonequivalent exocyclic 1,3‐butadienes(dimethylidenebicyclo[2.2.2]octene 3 and 2,3,5,6‐tetramethylidenebicyclo[2.2.2]‐octene ( 4 )) were investigated. In each cycloaddition, the reaction occurred via the course in which 1 added exclusively by its syn‐face (same face as the etheno‐bridge) onto either π‐face of the exocyclic 1,3‐butadiene systems to produce only two of the four possible stereoisomeric monocycloadducts ( 8a / 8b and 9a / 9b ). In the Diels‐Alder cycloaddition of 1 with bis‐exocyclic butadiene 4 , however, both monocycloadducts 9a and 9b underwent subsequent cycloaddition with distinctive facial selectivity to produce the C_s‐symmetric bis‐cyclohexanobarrelene 10a as only bis‐cycloadduct.     

An Unexpected Double Diels–Alder Reaction of (E)‐2‐Bromo‐4‐aryl‐1,3‐pentadiene Involving [1,5]‐Hydrogen Migration and HBr Elimination: Synthesis of Bicyclo[2.2.2]octene Derivatives

An unexpected double Diels–Alder (DDA) reaction of (E)‐2‐bromo‐4‐aryl‐1,3‐pentadiene was developed and resulted in a series of “butterfly‐like” bicyclo[2.2.2]octene derivatives in moderate to good yields without the need for a metal catalyst. The proposed mechanism involves a [1,5]‐sigmatropic hydrogen migration and HBr elimination. Through this decisive [1,5]‐hydrogen shift step, the electronic properties and steric hindrance of the conjugated diene substrate are completely altered and the DDA reaction of this potential diene synthon is successfully achieved.     

Copper‐Catalyzed Enantio‐, Diastereo‐, and Regioselective [2,3]‐Rearrangements of Iodonium Ylides

The first highly enantioselective, diastereoselective, and regioselective [2,3]‐rearrangement of iodonium ylides has been developed as a general solution to catalytic onium ylide rearrangements. In the presence of a chiral copper catalyst, substituted allylic iodides couple with α‐diazoesters to generate metal‐coordinated iodonium ylides, which undergo [2,3]‐rearrangements with high selectivities (up to >95:5 r.r., up to >95:5 d.r., and up to 97 % ee ). The enantioenriched iodoester products can be converted stereospecifically into a variety of onium ylide rearrangement products, as well as compounds that are not accessible by classical onium ylide rearrangements.     

Diazabicycloalkanes with nitrogen atoms in bridgehead positions 20. Synthesis of naphtho[2,3-b]-1,4-diazabicyclo[2.2.2]octene

Reaction of 2-acetamido-3-bis(2-hydroxyethyl)aminonaphthalene with phosphorus oxychloride leads to the formation of 2-methyl-1-(2-chloroethyl)naphtho[2,3-d]imidazole, while reaction with hydrobromic acid gives naphtho[23-b]-1,4-diozabicyclo[2.2.2]octane in 13% yield. The yield of the latter can be increased to 45% by exchange of the hydroxyl groups in the starting material by chlorine and by deacetylation.For Communication 19, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 97–100, January, 1991.     

Unprecedented 1,14‐seco‐Crotofolanes from Croton insularis: Oxidative Cleavage of Crotofolin C by a Putative Homo‐Baeyer–Villiger Rearrangement

EBC‐162 isolated from Croton insularis, obtained from the northern rainforest of Australia, was structurally affirmed as crotofolin C ( 4 ). Novel oxidative degradation products, EBC‐233 and EBC‐300, which are the first crotofolane endoperoxides, were also isolated. Both endoperoxides were found to be stable intermediates, which are proposed to undergo an unprecedented homo‐Baeyer–Villiger biosynthetic rearrangement to give a new class of 1,14‐seco‐crotofolane diterpenes. Prolonged storage of all isolates assisted in authenticating their natural product status. Anticancer activities of reported compounds are presented.     

Unexpected Approach to the Synthesis of 2‐Phenylquinoxalines and Pyrido[2,3‐b]pyrazines via a Regioselective Reaction

An unexpected approach to the preparation of quinoxaline and pyrido[2,3‐b]pyrazine derivatives 5 is described. The reaction between 1H‐indole‐2,3‐diones 1 , 1‐phenyl‐2‐(triphenylphosphoranylidene)ethanone ( 2 ), and benzene‐1,2‐ or pyridine‐2,3‐diamines 3 proceeds in MeOH under reflux in good to excellent yields (Scheme 1 and Table). No co‐catalyst or activator is required for this multi‐component reaction (MCR), and the reaction is, from an experimental point of view, simple to perform. The structures of 5, 5′ , and 6 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and were confirmed by comparison with reference compounds. A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Synthesis of Some New 6,8‐Disubstituted 7,8‐Dihydropyrimido[2,3:4,3]pyrazolo[1,5‐a]pyrimidines and 6,7,8‐Trisubstituted Pyrimido[2,3:4,3]Pyrazolo[1,5‐a]Pyrimidine Derivatives

Cyclization of 5‐cyano‐1,6‐dihydro‐4‐methyl‐2‐phenyl‐6‐thioxopyrimidine 4 with excess of 85% hydrazine hydrate afforded the 3‐amino‐4‐methyl‐6‐phenylpyrazolo[3,4‐d]pyrimidine 5 , which can react with appropriate Mannich base derivatives 13a‐c and chalcones 27a,b to yield the corresponding 6,8‐disubstituted 7,8‐dihydropyrimido[2,3:4,3]pyrazolo[1,5‐a]pyrimidines 15a‐c and 30a,b , respectively. On the other hand, the 6,7,8‐trisubstituted pyrimido[2,3:4,3]pyrazolo[1,5‐a]pyrimidine derivatives 8a‐g, 20a‐e, 36 and 38 were obtained by treatment of compound 5 with appropriate 1,3‐diketones 6a‐g , 3‐dimethylamino‐1‐(substituted)prop‐2‐enones 18a‐e , 3‐aminocrotononitrile 3 , and ethoxymethylenemalononitrile 37 under acidic condition, respectively.     

DFT study on the hydrogen bonds of phenol–cyclohexanone and phenol–H2O2 in the Baeyer–Villiger oxidation

Hydrogen bonds of phenol–cyclohexanone and phenol–H₂O₂ in the studied Baeyer–Villiger (B–V) oxidation have been investigated by HF, B3LYP, and MP2 methods with various basis sets. The accurate single‐point energies were performed using CCSD(T)/6‐31+G(d,p) and CCSD(T)/aug‐cc‐pVDZ on the optimized geometries of MP2/6‐31+G(d,p). It has been confirmed that B3LYP/6‐31+G(d,p) could be used to study such hydrogen bonds. Energetic analysis of complexes was carried out using the Xantheas method with BSSE corrected by CP method. Orbital energy order (ε) illuminated that phenol with good hydrogen donor‐acceptor property can interact with cyclohexanone or H₂O₂ to form hydrogen bound complexes, and the binding energies (BE) range from ?4.38 to ?14.06 kcal mol^?1. NBO analysis indicated that the redistribution of atomic charges in the complexes facilitated nucleophilic attack of H₂O₂ on cyclohexanone. The calculated results match remarkably well with the experimental phenomena. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

Short Synthesis of Enantiopure Thieno[2,3‐f]triazolo[1,5‐a][1,4]diazepines and Thieno[2,3‐f][1,4]diazepin‐5‐ones

Starting from 2‐carboxy‐3‐thenylazide 1 and enantiopure amines 2 as the chiral building blocks, we developed a two‐step synthesis of the title compounds involving an intramolecular azide cycloaddition as the key step.     

Nanomagnetically modified thioglycolic acid (γ‐Fe2O3@SiO2‐SCH2CO2H): Efficient and reusable green catalyst for the one‐pot domino synthesis of spiro[benzo[a]benzo[6,7]chromeno[2,3‐c]phenazine] and benzo[a]benzo[6,7]chromeno[2,3‐c]phenazines

Superparamagnetic nanoparticles of modified thioglycolic acid (γ‐Fe₂O₃@SiO₂‐SCH₂CO₂H) represent a new, efficient and green catalyst for the one‐pot synthesis of novel spiro[benzo[a ]benzo[6,7]chromeno[2,3‐c ]phenazine] derivatives via domino Knoevenagel–Michael–cyclization reaction of 2‐hydroxynaphthalene‐1,4‐dione, benzene‐1,2‐diamines, ninhydrin and isatin. This novel magnetic organocatalyst was easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused at least six times without significant loss in its activity. The catalyst was fully characterized using various techniques. This procedure was also applied successfully for the synthesis of benzo[a ]benzo[6,7]chromeno[2,3‐c ]phenazines.     

catena‐Poly[1,4‐dihydroxy‐1,4‐diazoniabicyclo[2.2.2]octane [aquatri‐μ‐chlorido‐trichloridodicuprate(II)]]

The title compound, {(C₆H₁₄N₂O₂)[Cu₂Cl₆(H₂O)]}_n, consists of 1,4‐dihydroxy‐1,4‐diazoniabicyclo[2.2.2]octane dications and one‐dimensional inorganic anionic {[Cu₂Cl₆(H₂O)]²⁻}_n chains in which both five‐coordinate [CuCl₃(H₂O)]⁻ and five‐coordinate [CuCl₃]⁻ units exist. These two distinct type of unit are linked together by one chloride ion and are bridged across centres of inversion to further units of their own type through two chloride ions, giving rise to novel polymeric zigzag chains parallel to the c axis. The chains are connected by O—H...Cl hydrogen bonds to produce R₂⁴(16) ring motifs, resulting in two‐dimensional layers parallel to the ac plane. These layers are linked into a three‐dimensional framework with the organic cations via O—H...Cl hydrogen bonds. Hydrogen bonding between the chains, and between the chains and the organic cations, provides stability to the crystal structure.