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Photoirradiation of the titled compounds perfluoro- cis -1,2-dimethyl-butadienyl benzenes ( 1 ), which were prepared in several steps from perfluorovinyl bromide, results in the formation of the corresponding novel naphthalene derivatives and 1,4-dihydronaphthalenes. Isolated 1,1,2-trifluoro-3,4-bis(trifluoromethyl)-1,4-dihydronaphthalene ( 3a ) could be converted into 1,2-bistrifluoromethyl-3,4-difluoronaphthalene ( 2a ) by base treatment (DABCO); however, 3a did not lead to 2a by photoreaction, suggesting 3a was not a possible photochemical precursor. Competitive photoreaction studies suggest that varying the substituent on benzene ring (e.g. methyl or trifluoromethyl) does not significantly affect the reaction rate. Presently, this reaction mechanism is not yet clearly understood.

Zinc centers in pseudo-tetrahedral geometry are widely found in biology, often with three histidine ligands from protein. The trispyrazolylborate “scorpionate” ligand is used as a model for this tris(histidine) motif, and spectroscopically active CoII is often used as a substitute for spectroscopically silent ZnII. In this work, four pseudo-tetrahedral scorpionate complexes with the formula (Tpt-Bu,Tn)CoL, where Tpt-Bu,Tn = hydrotris(3-tert-butyl, 5–2′-thienyl-pyrazol-1-yl)borate anion and L = Cl−, N3−, NCO−, or NCS−, were studied using variable-temperature, variable-field magnetic circular dichroism (VTVH MCD) spectroscopy. The major goal was to determine the axial and rhombic zero field splitting (ZFS) parameters (D and E, respectively) of these S = 3/2 systems and compare these ZFS parameters to those determined previously by high-frequency and -field electron paramagnetic resonance (HFEPR) spectroscopy on the same (L = Cl− and NCS−) or closely related complexes. Additionally, HFEPR studies were undertaken here on the complexes with L = N3−, NCO−. Crystal structures for these two complexes are also first reported here. The values of D determined by VTVH MCD were + 12.8 and + 3.6 cm−1 for the L = Cl− and NCS- complexes, respectively. These values are in close agreement with those for the same complexes as previously determined by HFEPR. The values of D determined by VTVH MCD were + 3.0 and + 6.6 cm−1 for the L = N3− and NCO- complexes, respectively. These values were not as close to those determined by HFEPR in the present study, which are 4.2 cm−1 ≤ |D| ≤ 5.6 cm−1 in Tpt-Bu,TnCoN3, and 8.3 cm−1 ≤ |D| ≤ 11.0 cm−1 in Tpt-Bu,TnCoNCO. The bands in MCD spectra of these complexes were assigned in C3v symmetry and a complete ligand-field analysis of the MCD data was made using the Angular Overlap Model (AOM), which is compared to previous results.

We have prepared and characterized two ruthenium(II) complexes supported by phosphine-functionalized N-heterocyclic (NHC) ligands. One of the complexes (2a) underwent ortho-metalation of the N-phenyl moiety giving rise to a tridentate PCNHCC− coordinating ligand whereas 2b bears an N-mesityl group in order to prevent C–H activation of the aryl ring thereby enforcing a PCNHC bidentate binding mode. Both 2a and 2b were shown to catalyze transfer hydrogenation of ketones at 82 °C in 2-propanol in the presence of KOtBu albeit with vastly different catalytic activities. Catalytic transfer hydrogenation by 2b was shown to proceed at room temperature and in air using unpurified 2-propanol as solvent and hydrogen donor. Time studies revealed unique kinetic profiles for the two precatalysts; this may shed light on the difference in their catalytic activities.

Two tetraarylethylene derivatives symmetrically functionalized at the 4, 4′, 4″, and 4 ‴ positions with either 4-pyridyl or 3-pyridyl groups were converted to their corresponding tetrapyridinium perchlorate salts upon exposure to Fe(ClO4)3·xH2O. These tetra-perchlorates were isolated as single crystals and their structures were determined by X-ray diffractometry. In both cases extensive hydrogen bonding networks were observed involving pyridinium N–H groups, perchlorate anions, and included water molecules. Additionally, both structures feature hydrophobic crystalline regions formed from stacking of tetraarylethylene cations in helical fashion. Polar pyridinium N–H groups are directed outward from these stacks into hydrophilic crystalline regions containing perchlorate anions and water molecules of hydration. Information obtained regarding the solid state structures of these functionalized tetraarylethylene derivatives should prove useful in design of more elaborate supramolecular architectures.

Two tetrapyridyl-substituted tetraphenylethylenes have been prepared via Suzuki coupling between tetrabromo tetraphenylethylene and 3- or 4-pyridine boronic acid. Both compounds exhibit aggregation-induced emission as determined by solid state fluorescence spectroscopy and solution phase fluorescence measurements performed in aqueous/organic solvent mixtures. Solution phase fluorescence was also found to be switchable as a function of pH. 3-Pyridyl-substituted tetraphenylethylene has been structurally characterized by X-ray crystallography.

The cis-fused hexahydroxanthene system can be obtained through a cascade cyclization initiated by Lewis acid-mediated epoxide opening and terminated by reaction with a MOM-protected phenol. Only a single diastereomer of the product was obtained with stereochemistry verified by diffraction analysis. This demonstrates the viability of this approach to natural products containing the cis-fused hexahydroxanthene skeleton, and supports preparation of more complex targets through a similar strategy.

The organoditantalum complexes (η-C5Me5)2Ta2(μ-X)4 (X = Cl, Br) react with 1–5 equiv. of allene under mild conditions to afford the fluxional allene adducts (C5Me5)2Ta2(μ-η1,η3-C3H4)(μ-X)X3 as shown by spectroscopic and spectrometric data. Low-temperature-limit proton NMR data at −95 °C for (C5Me5)2Ta2(μ-η1,η3-C3H4)(μ-Cl)Cl3 show a large chemical shift range for the inequivalent allene hydrogens, with a high-field value for one hydrogen at δ −0.36, and inequivalent Cp* groups. The low-temperature-limit 13C NMR resonances for the allene ligand are found at δ 204.4 (central C), δ 70.3 (CH2, 1JCH = 154 Hz), and the substantially upfield value of δ 42.9. The latter resonance has remarkably different coupling constants (1JCH = 173, 154 Hz). The allene coordinates in a novel alkylidene-diyl fashion in the solid-state, as shown by X-ray diffractometry on (C5Me5)2Ta2(μ-η1,η3-C3H4)(μ-Cl)Cl3 at 200 K. One tantalum is doubly-bonded to the central allenic carbon (Ta1 C22 distance, 2.011(7) A) and interacts with an allene hydrogen in a probable β-agostic manner (Ta1–H21A distance of 2.25(10) A). The second tantalum is coordinated to the allene in a hybrid of η3-allylic and sigma bonding, with Ta2–C distances to the allene methylenes of 2.206(8) and 2.276(9) A and a Ta2–C22 bond distance to the central allenic carbon of 2.253(7) A. The allene hydrogens are oriented above and below the C–C–C plane, consistent with appreciable σ-bonding between the Ta(2) and the allene methylenes. The bent allene ligand has a C–C–C angle of 106.0(6)° and can be viewed as reduced by four electrons, with concomitant oxidation of the two d2 tantalum centers of the organoditantalum(III) reactant. The long Ta⋯Ta nonbonded distance of 3.3052(8) A is consistent with two d0 tantalum centers in an organoditantalum(V) product.

The asymmetric synthesis of both enantiomers of modafinil, a unique CNS stimulant with a reduced abuse liability, is described. This approach effectively prepares modafinil on a multigram scale in several steps from benzhydrol. The described synthetic route has also been used to produce the more water soluble analogue, adrafinil. X-ray crystallographic analysis on (−)-(diphenylmethanesulfinyl)acetic acid has determined the absolute configuration to be R.

Malettinin A (1) has been isolated from cultures of an unidentified fungus encountered as a colonist of Hypoxylon stromata. The structure of 1 was proposed by analysis of NMR and MS data, and confirmed by X-ray diffraction analysis of a methanol adduct. Malettinin A shows significant activity in assays against Aspergillus flavus.

The terminal (diphenylalkenyl)alkylidene complexes (C5Me4R)Ta(CHCHCPh2)X2 (R=Me, Et; X=Cl, Br) are formed in moderate yields from the ring-opening reaction of 3,3-diphenylcyclopropene with the organoditantalum(III) halides (η-C5Me4R)2Ta2(μ-X)4. Potassium amalgam reduction of these alkenylalkylidene complexes afforded the alkylidene-tethered tantallanorbornadienes (C5Me4R)Ta[CHCHCPh(σ2-C6H5)], which possess a bent, boat conformation σ2-arene ligand with a fold angle of 19.24(46)° (R=Me) in the solid state. 13C and 1H NMR spectroscopies are consistent with a rapid flip-flop motion that averages the resonances of the σ2-phenyl group to fewer resonances than expected from the solid-state structure.

Palladium(0) catalyzed coupling of β-bromostyrene (E/Z = 89/11) with (E)-(1,2-difluoro-1,2-ethenediyl)bis[tributylstannane], 1, in DMF at room temperature stereospecifically gave only (1E,3E,5E)-3,4-difluoro-1,6-diphenylhexatriene. Similarly, palladium(0) catalyzed coupling of (E)-ethyl 3-bromoacrylate as the vinyl halide precursor stereospecifically gave (2E,4E,6E)-diethyl-4,5-difluoroocta-2,4,6-trienedioate. This work demonstrates that a non-fluorine-containing vinyl bromide will selectively undergo coupling with 1 and enable the stereospecific preparation of a mixed polyene system. The (E)-ethyl 3-bromoacrylate coupling with 1 illustrates that mixed functionalized hexatriene systems can be easily accessed via this methodology. The X-ray structure of (2E,4E,6E)-diethyl-4,5-difluoroocta-2,4,6-trienedioate confirmed its structure.

Chaetochalasin A (1), a new bioactive fungal metabolite with a previously undescribed ring system, has been isolated from an EtOAc extract of Chaetomium brasiliense (NRRL 22999). The structure of 1 was determined by NMR experiments and single-crystal X-ray diffraction analysis.

The reaction of [Z]-1,1,2,5,5,5-hexafluoro-4-phenyl-3-trifluoromethyl-1,3-pentadiene (1), prepared in several steps from perfluorovinyl bromide (3), and pyridine results in the formation of the 4-quinolizone derivatives 6 and 7. The reactions of [Z]-1,1,2,5,5,5-hexafluoro-4-iodo-3-trifluoromethyl-1,3-pentadiene (2), also prepared from perfluorovinyl bromide (3), and pyridine derivatives result in the formation of the 4-quinolizone derivatives 8-10. Since the observed cycloaddition reaction would have been expected to proceed with inverse electron demand, the facile reaction of 1 and 2 with pyridine provides a unique entry to the 4-quinolizone derivatives.

Massarilactones A and B ( 1 and 2 ) have been isolated from cultures of the freshwater aquatic fungus Massarina tunicata. The structures, including absolute stereochemistry, were determined by X-ray diffraction analysis of their bis(4-bromobenzoate) derivatives.

Louis Messerle, PhD,*1,2 Donald Nolting, BS1, Lizann Bolinger, PhD3, Alan H. Stolpen, MD/PhD2, Brian F. Mullan, MD,2 Dale Swenson, PhD,1 and Mark Madsen, PhD2 1Department of Chemistry, The University of Iowa, Iowa City IA 52242, 2Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, 3National Research Council Canada, Institute for Biodiagnostics, Winnipeg, MB, R3B 1Y6

Analysis of X-ray crystallographic data on steroids provides information concerning preferred conformations, relative stabilities, and substituent influence on the interactive potential of steroid hormones. Analysis of the data on the 4-ene-3-one ring indicates that it normally has a conformation midway between the 1α,2β-half chair and the 1α-sofa forms. Strain introduced into the molecule by substitution on the fused ring system shifts the A-ring conformation toward the more symmetric forms with an attendant change in the conjugation of the 4-ene-3-one system. Crystallographic data on 85 pregnane structures having a 20-one substituent provide information on 17β-side chain flexibility. In eighty-one structures the C(16)-C(17)-C(20)-O(20) torsion angle is between 0° and −46°. This is consistent with CD, i.r. and n.m.r. solution spectra and more precisely defines the side chain conformation in solution. The four structures whose side chains lie outside this range do so because of the presence of a 16β-substituent and not because of crystal packing forces. The steroid A ring appears to be primarily responsible for initiating and maintaining hormone binding to the estrogen and progestin receptors. When the structures of agonists and antagonists of specific steroid hormones are compared, they generally exhibit similarities in their A-ring region and dissimilarities in the D-ring region further suggesting that the steroid A-ring bears responsibility for receptor binding while the D-ring controls expression of activity. Antihormoncs that compete for the receptor site of a steroid hormone may be expected to have structural features appropriate for receptor binding (A-ring composition and conformation) and lack structural features that induce or stabilize subsequent receptor functions (D-ring conformatjonal features and functional groups).

The alpha- and beta-anomers of the 17 beta-D-glucuronide conjugate of ethynylestradiol were synthesized by the SnCl4-promoted reaction between beta-acetoxy GAM and the t-17 beta-hydroxyl group of EE2-3-acetate. The conjugates were resolved by crystallization and HPLC. Positive identification was established by u.v. spectrophotometry, i.r. and mass spectrometry and 1H- and 13C-n.m.r. The structure of the beta-anomer was confirmed by X-ray crystallographic analysis. In addition, the alpha-anomer was refractory to hydrolysis by bovine beta-glucuronidase, establishing a biochemical difference between the conjugate pair.

The catechol estrogens have varying degrees of affinity for the estrogen receptor, catecholamine enzymes and the dopamine receptor. The X-ray crystal structures of 2-hydroxyestradiol, 2-hydroxyestrone and 4-hydroxyestrone are reported here and compared with those of estradiol, estrone, dopamine and apomorphine. The overall molecular shapes and hydrogen bonding patterns have been examined for possible relevance to protein binding and activity. The principal structural observations and their potential significance are the following: (1) The 4-hydroxyestrone results indicate that the 4-substituent does not constitute a steric impediment to estrogen receptor binding but does restrict the probable location of the hydrogen bond acceptor atom on the receptor. (2) The reduced affinity of 2-hydroxyestradiol for the estrogen receptor may be due to a combination of steric interaction and interference with hydrogen bond formation of O(3). (3) The reduced affinity of 17-one substituted steroids in this series for the estrogen receptor most strongly supports the probable importance of a hydrogen bond donor at that position interacting directly with the receptor. (4) In the catechol estrogens the formation of an intramolecular and two or more intermolecular hydrogen bonds together with the extension of the A ring's planar surface to include the hydroxyl substituents and part of the B ring must account for its high binding affinity for catechol amine related enzymes, the dopamine receptor and a putative catechol estrogen receptor. (5) Two orientations of the catechol estrogens relative to that of dopamine when bound to its receptor are suggested by this study. One achieves maximum overlap of the hydrogen bond pattern of the dihydroxy benzene ring and the other maximizes similarity in overall shape. The results of this investigation are consistent with the hypothesis that the A-ring plays a primary role in initiating estrogen binding to its receptor and suggests an even more highly specific A-ring interaction with the dopamine receptor and catechol amine enzymes.