7-Selenabicyclo[2.2.1]heptane

Abstract

a b s t r a c tAb initio and density functional theory (DFT) calculations predict that intramolecular homolytic substitution by alkyl radicals at the selenium atom in seleninates proceeds through smooth transition states in which the attacking and leaving radicals adopt a near collinear arrangement. When forming a fivemembered ring and the leaving radical is methyl, G3(MP2)-RAD calculations predict that this reaction proceeds with an activation energy (DE 1 z ) of 30.4 kJ mol . Homolytic addition to the phenyl group was found not to be competitive with substitution, with a calculated barrier of 57.6 kJ mol À1. This computational study provides insight into homolytic substitution chemistry involving seleninates.

The quest for selenocycles: From an ESR spectrum to a commercial product

“…The rate scale spans almost 46 orders of magnitude, from the ring-closure at methyl sulfone 8 (calculated to be 5 × 10 −37 s −1 at 25 °C; that is, sulfones do not react) to cyclization at telluride 9 (determined to be 5 × 10 8 s −1 at 25 °C) (Figure 2). 16,21–30 The lack of reactivity shown by sulfones and selenones led to closer inspection of the reaction mechanism, which was revealed to require at least one lone pair of electrons (Figure 3) to be successful, 30 thereby differentiating it from the well-accepted S N 2 mechanism. Indeed, the SOMO of the radical interacts simultaneously with both the lone pair (LP) on sulfur and the C–S σ* orbital.…”

“…Examples include selenotocopherol analogue 10 (in collaboration with Lars Engman, who later prepared α-selenotocopherol), 35,36 pyrido analogue 11 , 37 allosteric enhancer 12 and agonist 13 of the A 1 adenosine receptor (in collaboration with Peter Scammells), 38,39 antibiotic lookalikes 14 and 15 , 40 selenomilfasartan ( 16 ) and selenoeprosartan ( 17 ) (antihypertensives), 41,42 protected selenosugars 18 and 19 , 43 fused heterocycle 20 , 44 and 7-selenabicyclo[2.2.1]heptane ( 21 ). 25…”

“…Examples include selenotocopherol analogue 10 (in collaboration with Lars Engman, who later prepared α-selenotocopherol), 35,36 pyrido analogue 11, 37 allosteric enhancer 12 and agonist 13 of the A 1 adenosine receptor (in collaboration with Peter Scammells), 38,39 antibiotic lookalikes 14 and 15, 40 selenomilfasartan ( 16) and selenoeprosartan (17) (antihypertensives), 41,42 protected selenosugars 18 and 19, 43 fused heterocycle 20, 44 and 7-selenabicyclo[2.2.1]heptane (21). 25 Is it worth mentioning here that commercializing selenium-containing compounds can be particularly difficult. Selenium has been unfairly (blanket) labeled as "toxic," often by individuals who don't really understand the importance of molecular structure.…”

The effect of leaving radical on the formation of tetrahydroselenophene by SHi ring closure: an experimental and computational study

“…16 Some of this work has been experimentally driven and has employed competition kinetics as well as laser-flash photolysis (LFP) techniques, 3,[17][18][19] however, when precursors have been difficult to prepare or handle, or the chemistry has been difficult, we have also resorted to highlevel computational techniques to provide kinetic information. 5,13,20 Somewhat ironically, since our original publication in 1992, 1 we have still not determined kinetic parameters for the cyclization of the "parent" 5-(benzylseleno)pentyl radical (1, R = Bn). In this paper we rectify this long-overdue anomaly and report both experimentally and computationally determined rate constants and Arrhenius parameters for the ringclosure of 1, and related systems that include a variety of leaving radicals, including benzyl (Scheme 2).…”

The kinetics of alkyl radical ring closures at selenium: formation of selenane

“…7,8 We reasoned that since the cyclization of the 4-(tert-butylthio)butyl radical 2 proceeded with a rate constant of 6.9 × 10 3 s −1 (80°), 9 and given that phenylselenides react two to three orders of magnitude faster with tributyltin radical than the corresponding phenylsulfide, 10 the rate constant (k c ) for the ring closure of 1 had to be of the order of 10 5 -10 6 s −1 at 80°. These assumptions ultimately proved to be helpful, and since these early days we have utilized homolytic substitution chemistry at benzylselenides to construct a large variety of selenium-containing ring systems, [11][12][13][14][15][16] some of which have proven to be useful in medicinal chemistry. An example is selenomilfasartan 3, an antihypertensive, in which the selenophene ring is constructed using this chemistry (Scheme 3).…”