Carl H. Schiesser

Preparation of 5-Selenopentopyranose Sugars from Pentose Starting Materials by Samarium(II) Iodide or (Phenylseleno)formate Mediated Ring Closures

Abstract 2,3,4-Tri-O-benzyl-1,5-dideoxy-5-seleno- d -pentopyranose sugars (16, 23, 24) are readily prepared by thermolysis of 2,3,4-tri-O-benzyl-5-benzylseleno- d -ribit-1-yl formate, 2,3,4-tri-O-benzyl-5-benzylseleno- d -xylit-1-yl formate and 2,3,4-tri-O-benzyl-5-benzylseleno- d -arabit-1-yl formate (13, 21, 22) in transformations which involve intramolecular nucleophilic attack of the benzylseleno moiety with concomitant loss of carbon dioxide and phenylselenoate. In a complementary procedure, treatment of 2,3,4-tri-O-benzyl-5-benzylseleno-5-deoxyribose (19) with samarium(II) iodide in THF affords 2,3,4-tri-O-benzyl-5-deoxy-5-seleno- d -ribopyranose (26) in 50% isolated yield in a process most likely involving intramolecular homolytic substitution at the selenium atom in the selenosugar.

Selenosartans: novel selenophene analogues of milfasartan and eprosartan.

A series of selenophene analogues of the thiophene-containing antihypertensives milfasartan and eprosartan were prepared and tested for AT(1) receptor antagonist properties. All four selenophene compounds proved to be potent AT(1) receptor antagonists, with pK(B) estimates indicating that these selenides are at least as effective as the thiophene parent compounds at blocking AT(1) receptor mediated responses. These results reveal that replacement of sulfur with selenium in thiophene-containing sartans does not interfere with sartan activity.

An ab initio study of some free-radical homolytic substitution reactions at sulfur, selenium and tellurium

Abstract Ab initio molecular orbital calculations using pseudopotential basis sets and electron correlation (MP2, QCISD) predict that homolytic substitution by methyl, silyl, germyl and stannyl radicals at the chalcogen atom in methanethiol, methaneselenol and methanetellurol, with the expulsion of methyl radical, proceeds smoothly. With the exception of dimethyl- λ 4 -tellanyl at the MP2 and QCISD levels of theory, no hypervalent (9-E-3) intermediates were located in any of the reactions in this study. Reactions of germyl and stannyl radicals at methaneselenol and methanetellurol are predicted to be reversible.

Cyclizative radical carbonylations of azaenynes by TTMSS and hexanethiol leading to α-silyl- and thiomethylene lactams. Insights into the E/Z stereoselectivities

Free-radical mediated cyclizative carbonylations of azaenynes were carried out using TTMSS as a radical mediator to compare the efficiency and the stereochemistry with those using tributyltin hydride. Using a substrate concentration of 0.1 M, the reactions gave good yields of alpha-silylmethylene lactams having four to seven-membered rings. The observed E-diastereoselectivity of the resulting vinylsilane moiety is in sharp contrast to the Z-selectivity observed during the analogous carbonylation using tributyltin hydride. When hexanethiol was used as the radical mediator, alpha-thiomethylene lactams were formed with E-favoring stereoselectivity again. Ab initio and DFT molecular orbital calculations on the stability of E and Z products were carried out for a set of five-membered methylene lactams bearing SnH3, SiH3, and SMe groups. The distinct thermodynamic preference for the Z-isomer was only predicted for the Sn-bearing lactam. A steric effect due to the bulky (TMS)3Si group is proposed for the E-selectivity observed in the TTMSS-mediated reaction.

Radicals masquerading as electrophiles: a computational study of the intramolecular addition reactions of acyl radicals to imines

Ab initio calculations using 6-311G**, cc-pVDZ, and aug-cc-pVDZ, with (MP2, QCISD, CCSD(T)) and without (UHF) electron correlation, and density functional methods (BHandHLYP and B3LYP) predict that cyclization of the 5-aza-5-hexenoyl and (E)-6-aza-5-hexenoyl radicals proceed to afford the 5-exo products. At the CCSD(T)/cc-pVDZ//BHandHLYP/cc-pVDZ level of theory, energy barriers (deltaE(double dagger)) of 36.1 and 47.0 kJ mol(-1) were calculated for the 5-exo and 6-endo pathways for the cyclization of the 5-aza-5-hexenoyl radical. On the other hand, at the same level of theory, deltaE(double dagger) of 38.9 and 45.4 kJ mol(-1) were obtained for the 5-exo and 6-endo cyclization modes of (E)-6-aza-5-hexenoyl radical, with exothermicities of about 27 and 110 kJ mol(-1) calculated for the exo and endo modes, respectively. Under suitable experimental conditions, the 6-endo cyclization product is likely to dominate. Analysis of the molecular orbitals involved in these ring-closure reactions indicate that both reactions at nitrogen are assisted by dual orbital interactions involving simultaneous SOMO-pi* and LP-pi* overlap in the transitions states. Interestingly, the (Z)-6-aza-5-hexenoyl radical, that cannot benefit from these dual orbital effects is predicted to ring-close exclusively in the 5-exo fashion.

On the existence of SH3, SeH3, and TeH3: Discrepancies between all‐electron and pseudopotential calculations

Ab initio calculations using both pseudopotential and double and triple‐ζ all‐electron basis sets, with and without electron correlation (MP2, QCISD), have been performed on the λ4‐sulfanyl (SH3), λ4‐selanyl (SeH3), and λ4‐tellanyl (TeH3) radicals. All‐electron basis sets of double‐ζ quality predict that SH3 and SeH3 correspond to transition states on their respective potential energy surfaces. In contrast, the pseudopotentials of Hay and Wadt predict that SH3 and SeH3 correspond to local minima at the QCISD level of theory while the pseudopotentials of Christiansen and Stevens predict transition states. By comparison, TeH3 proved to be a local minimum at all levels of theory. Interestingly, when a very large (triple‐ζ) all‐electron basis set was used, SH3 proved to be a transition state; however, in this instance the potential energy surface was found to be much flatter than in the case for which a double‐ζ basis set was used, suggesting that further improvements in the basis set may lead to a local minimum. Further improvements in the all‐electron selenium basis also led to a local minimum for SeH3 at the QCISD level of theory.

Thiols, thioethers, and related compounds as sources of C-centred radicals

Due to their stability, availability and reactivity, sulfides are particularly attractive sources of carbon-centered radicals. However, their reactivity in homolytic substitution processes is strongly reduced when compared with the corresponding selenides or halides. Despite this, sulfur-containing compounds can be engineered so that they become effective agents in radical chain reactions. A detailed description of the reactivity of organo-sulfur compounds is reported here with the aim of providing clear guidance on the scope and limitation of their use as radical precursors in chain reactions.

Reactions of 2,2′-diselenobis(N-alkylbenzamides) with peroxides: A free-radical synthesis of Ebselen and related analogues

Abstract N-Alkyl-2-triphenylstannylbenzamides (3, R = Hex, Ph, iso -Pro, tert -Bu), prepared from the corresponding 2-benzylselenobenzamides, react with benzoyl peroxide in benzene, under reflux, to afford the 2,2′-diselenobis(N-alkylbenzamides) ( 4 ) in 54–87% yield. Further treatment with benzoyl peroxide or di- tert -butyl peroxide in benzene or chlorobenzene affords the N-alkyl-1,2-benzisoselenazol-3(2H)-ones ( 2 ) in 76–85% yield. This transformation presumably involves intermediate amidyl radicals which undergo intramolecular homolytic substitution at selenium to afford the product.

Homolytic substitution by iminyl radical at selenium: A free-radical route to 1,2-benzoselenazoles

Abstract Thiohydroxamic esters ( 3 ) derived from the O-car☐ymethyl oxime derivatives ( 2 ) of 2-(benzylseleno)-benzaldehyde ( 1 : R = H), 2-(benzylseleno)acetophenone ( 1 : R = Me) and 2-(benzylseleno)propiophenone ( 1 : R = Et) decompose smoothly, upon irradiation, with the loss of carbon dioxide and formaldehyde to give the 1,2-benzoselenazoles ( 5 ). The reaction presumably involves the iminyl radical intermediate ( 4 ) which undergoes intramolecular free-radical homolytic substitution at selenium to afford the product ( 5 ).

First determination of the rate constant for ring-closure of an azahexenoyl radical: 6-aza-7-ethyl-5-hexenoyl

Competitive kinetic experiments utilising free radical carbonylation chemistry provide a first estimate for the rate constant for 6-endo cyclization of the 6-aza-7-ethyl-5-hexenoyl radical of (4.8 +/- 2.4) x 10(6) s(-1) at 90 degrees C in benzene, in good agreement with ONIOM-G3(MP2)-CC+COSMO-RS calculations (6.8 x 10(6) s(-1)).