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

Abstract

Dedicated to Prof. Dr. Kurt Schuffner on the occasion of his 60th birthday ( . 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.