Cathleen Wismach

Reactions of Organoselenenyl Iodides with Thiouracil Drugs: An Enzyme Mimetic Study on the Inhibition of Iodothyronine Deiodinase

The proposed mechanism of iodothyronine deiodinase inhibition by the thiourea-derived drugs 6-n-propylthiouracil (PTU) and 6-methylthiouracil is supported by experimental evidence. Model reactions with sterically or coordinatively stabilized organoselenyl iodides as enzyme-mimetic substrates (E-SeI; see scheme) support the proposal that PTU reacts not with the enzyme but with the enzyme-SeI intermediate containing a covalent Se-I bond, and suggest that the Se-I bond is kinetically activated by basic amino acid groups such as histidine.

Biomimetic Studies on Iodothyronine Deiodinase Intermediates: Modeling the Reduction of Selenenyl Iodide by Thiols

Enzyme mimetic studies on the crucial intermediate (E−SeI) of the iodothyronine deiodinase cycle have been carried out by using an areneselenenyl iodide stabilized by intramolecular Se⋅⋅⋅N interactions. Treatment of this compound with aromatic thiols and thiobenzoxazole in the presence of NEt3 affords areneselenenyl sulfides that are stable towards disproportionation reactions. The structures of three of the areneselenenyl sulfides were determined by X‐ray crystallography. In one case, in the absence of NEt3, a diselenide can be formed rather than the selenenyl sulfide. The areneselenenyl iodide also reacts with a related selenol to produce the corresponding diselenide, and this reaction is found to be much faster than that with thiols. The high reactivity of the selenenyl iodide with the selenol suggests that a reduced selenol group (R′−SeH) may react with the E−SeI intermediate to produce a diselenide (E−Se−Se−R′) without any thiol cosubstrate. The intermediacy of selenenyl sulfides during the reduction of selenenyl iodide by thiols and its possible relevance to the iodothyronine deiodinase catalytic cycle is also described.

Electrophilic terminal phosphinidene complex–Lewis base adducts: Chemistry between carbon–halide bond activation and weak Lewis base adduct formation

Comparative studies on the reactivity of a transiently formed terminal phosphinidene complex towards various organobromide derivatives show that carbon-bromine bond insertion is preferred with benzyl bromide, whereas formal HBr-insertion resulted with 2-bromopyridine and a surprising selectivity enhancement (of the phosphinidene complex) was observed with bromobenzene; all new products were established by elemental analyses, NMR spectroscopy, mass spectrometry and single crystal X-ray diffraction studies.

Synthesis of functional Δ3-1,3,5-oxazaphospholene and 2H-1,4,2-diazaphosphole complexes via catalytic ring expansion reactions of a 2H-azaphosphirene complex

Abstract Catalytically-induced ring expansion of 2H-azaphosphirene complex 1 using ferrocenium hexafluorophosphate and acetone ( 2 ), diethylketone ( 3 ), cyclohexanone ( 4 ), benzaldehyde ( 5 ) or para-hydroxy-benzaldehyde ( 6 ) furnished selectively the Δ3-1,3,5-oxazaphospholene complexes 7–11 , whereas with ortho- and para-hydroxy- or ortho- and para-amino-substituted benzonitriles the 2H-1,4,2-diazaphosphole complexes 16–19 were obtained. Two further findings are noteworthy: (1) The significant decreased reaction time in the case of the sterically more demanding carbonyl derivatives 2–4 and (2) the formation of diastereomers in the case of 10 and 11 with a ratio of 8:1 and 9:1, respectively. All products were characterized by NMR, MS and elemental analysis and the configuration of complexes 7 and 10a were determined by X-ray single-crystal diffraction analysis.

Synthesis of a C-pyridine-substituted 2H-1,3,2-diazaphosphole complex and subsequent oxidation to its PV-sulfide and PV-selenide derivatives

Abstract Thermal ring opening of 2H-azaphosphirene tungsten complex 1 in the presence of 2-piperidino carbonitrile and 2-cyanopyridine furnished selectively the 2H-1,3,2-diazaphosphole tungsten complex 3. Liberation of the diazaphosphole ligand by applying various decomplexation reagents failed. However, the corresponding PV-sulfide 4 and PV-selenide 5 were obtained by oxidative decomplexation using elemental sulfur and selenium. All products were characterized by NMR spectroscopy and MS spectrometry. The constitution of 3 and 5 could also be established by single crystal X-ray diffraction.

Di(phosphavinyl) ethers (2,4-diphospha-3-oxapentadienes)

Hydrolytic cleavage of the P-chlorophosphaalkenes (RMe2Si)2C=PCl (R = Me: 1a; R = iPr: 1b) in the presence of triethylamine leads to di(phosphavinyl) ethers (2,4-diphospha-3-oxapentadienes) [(RMe2Si)2C=P]2O (2a, 2b) as main products, accompanied by alkylphosphinic acids (RMe2Si)2(H)CP(H)(O)OH (3a, 3b). The hydrolysis of (PhMe2Si)2C=PCl (1c) proceeds less selectively. Reactions with metal oxides under aprotic conditions provide 2a [impure, from 1a with (nBu3Sn)2O] and 2b [from iodophosphaalkene (iPrMe2Si)2C=PI with Ag2O] as oils. 1H, 13C, 29Si and 31P NMR spectra, however, allow unambiguous characterisation of 2a and 2b. Formation mechanisms, structure, and C=P-O π stabilisation of the oxabisphosphaalkene [(H3Si)2C=P]2O (2ʹ) were studied with DFT methods. The double [2+4] cycloaddition reaction of 2a with two equivalents of cyclopentadiene leads to the phosphinous anhydride 7 as a mixture of diastereomers whereas the addition of two equivalents of tetrachloro-o-benzoquinone proceeds in a diastereoselective fashion. An X-ray crystal structure determination of the resulting oxo-bridged bis(2-phospha-2,5-dioxa-3,4-benzophospholene) derivative 8 revealed the presence of a racemic mixture of (R,R)- and (S,S)-configurated molecules. The solid state structure of a by-product, bisylphosphonic tetrachlorocatechol monoester (Me3Si)2CH-P(=O)(OH)-o-OC6Cl4OH 9, was also determined crystallographically. Graphical Abstract Di(phosphavinyl) Ethers (2,4-Diphospha-3-oxapentadienes)

Diastereoselective Reactions of Sulfur- and Selenium-Bridged Bisphosphaalkenes with Tetrachloro-o-benzoquinone

2,4-Diphospha-3-thia- and 3-selenapentadienes [(Me 3 Si) 2 C = P] 2 E ( 1a : E = S; 1b : Se) react as bifunctional phosphaalkenes with two equivalents of cyclopentadiene and of tetrachloro-o-benzoquinone (TOB), furnishing 2a and 2b from double [2+4] cycloaddition reactions of the diene and 3a and 3b from the reactions of TOB with the P = C double bonds. The phosphanorbornane-related chalcogenophosphinous anhydrides 2a and 2b are obtained as pairs of isomers, whereas the reactions with TOB proceed diastereoselectively. X-ray crystallographic data confirm that bis-dioxaphospholene-related 3b consists of a mixture of (RR) and (SS) enantiomers. A third equivalent of TOB can be added oxidatively to one phosphorus atom of 3a and 3b , furnishing the spirocyclic compounds 6a and 6b with P(σ < eqid1 > λ < eqid2 > 5 < eqid3 > 5 ) connectivity. 3a and 6a are configurationally stable at room temperature, whereas the selenium derivatives 3b and 6b undergo slow isomerisation in solution.

An unconventional route to [(Me3Si)2HCPCl2W(CO)5] and its conversion to the structurally characterized P-chalcogenides (Me3Si)2HCP(X)Cl2[X = S, Se]

Heating a solution of 2H-azaphosphirene complex 1 in CCl4 at 75 °C for 2 h yields selectively [(Me3Si)2HCPCl2W(CO)5] (6). Attempts to convert this cleanly to the corresponding P-oxide [(Me3Si)2HCP(O)Cl2] (7) were unsuccessful and even the reaction of (Me3Si)2HCPCl2 (9) with the urea–H2O2 adduct in toluene led only to the formation of the hydrolysis product [(Me3Si)2HCP(O)(OH)Cl] (8). However, 9 could be selectively converted to 7 by the use of DMSO. In contrast, the related chalcogenides [(Me3Si)2HCP(S)Cl2] (10) and [(Me3Si)2HCP(Se)Cl2] (11) could be synthesized from either 6 or 9 with elemental sulfur and selenium, respectively. All products were characterized by NMR and MS and, additionally 6, 8, 10 and 11 by single crystal X-ray studies. Compound 10 represents the first example of a structurally characterized thiophosphonic dihalide.

2,4,6‐Tripiperidino‐1,3,5‐triazine

In the title compound, C18H30N6, the central triazine ring is planar, with C—N bond lengths 1.3415 (14)–1.3504 (13) A, N—C—N angles 125.58 (10)–125.97 (9)° and C—N—C angles 113.82 (9)–114.33 (9)°.

Synthesis of the first 1,2,3,4-azatriphospholene complex

Synthesis of the first 1,2,3,4-azatriphospholene complex was achieved by heating a solution of a P-phenyl-substituted 7-phosphanorbornadiene tungsten complex and triphenylphosphonio cyanomethylide, whereby CH-insertion products were formed in a competing reaction; these results also provide first evidence for the ability of electrophilic terminal phosphanediyl complexes to react at the ylide carbon atom and at the carbonitrile nitrogen atom of Wittig-ylides having a nitrile functional group; the structures of both complexes were established through X-ray single-crystal diffraction studies.