Photo-oxygenation of Styrenic Estrogens: Structural Analysis of 8,9-Didehydro-, 6,7-Didehydro-, and 9,11-Didehydroestrone Derivatives and Their Reactivity towards Singlet Oxygen
✍ Scribed by Carles Malet; Antoni Planas; Carme Brosa; Juan F. Piniella; Jordi Rius
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- German
- Weight
- 839 KB
- Volume
- 74
- Category
- Article
- ISSN
- 0018-019X
No coin nor oath required. For personal study only.
✦ Synopsis
Dedicated to Prof. Dr. Kurt Schuffner on the occasion of his 60th birthday ( 5 . V111.91)
A series of didehydro-3-0 -methyl-estrones having a styrenic framework, with the ring-A-conjugated double bond in all three possible positions (8,9-didehydro-(6), 9,1 I-didehydro-(lb), 6,7-didehydro-(9), and the 12,18-dinor-8,9-didehydroestrone analog 1 l), were compared for their reactivity towards singlet oxygen. Under dye-sensitized photo-oxygenation conditions, both, products derived from ene-type reactions with the isolation of a stable hydroperoxide and a fragmentation product, were obtained from 6 (see Scheme 3 ) , while only fragmentation took place for l b (Scheme I ) . Kinetic studies indicated that 6 is more reactive towards '0, than l b (B = 9.2.
mol. I-' us 3.3. lo-' mol.I-', resp.). The observed reactivity, apparently, does not match with ene-type reaction and [2 + 2]cycloaddition being in competition, since the most activated substrate 6 preferentially yields ene-type products and their derivatives. Conformational analysis on the structure of 6 and lb, both calculated by molecularmechanic techniques (MMPMI) and determined by X-ray diffraction, show that the allylic H-atoms satisfy the orthogonality rule for ene-type reactions. The product distribution is best rationalized by applying Fukui's rule which takes into account a combination of electronic and geometric factors. Substrates 9 and 11 yielded photoproducts arising from ene-type reaction with no stable primary products isolated (Scheme 4 ) . Geometric considerations based on the calculated structures by molecular mechanics are consistent with the observed results. Scheme 1 1413 2 18 R=H b R=Me c R=Ac d R=Bz e R=Ts 3 9,l I-didehydroestrone derivatives la-(Scheme I) [4] [5]. These activated p-substituted styrene substrates showed different reactivity and yielded different products depending on the substitution at C( 3), e.g. 2 and 3 when R was H and Me, respectively. The C-seco-aldehyde 3 arises from an oxidative cleavage of the C( 9)=C( 1 1) bond of lb; the intermediacy of a 1,2-dioxetane as primary photo-oxygenation product was suggested, although no direct evidence was provided. This oxidative fragmentation allowed the design of a short synthesis of 1 I-oxaestrogens from estrone in nine steps [6].
In the present study, we report the behaviour towards singlet oxygen of other styrenic estranes with the ring-A-conjugated double bond in positions 8,9 or 6,7. Conformational calculations and X-ray structures of a set of styrenic substrates are described in order to rationalize their differential reactivity in terms of geometric and electronic factors.