Ene-thiol reaction of C3-vinylated chlorophyll derivatives in the presence of oxygen: synthesis of C3-formyl-chlorins under mild conditions

Abstract

Reactions of thiol with the C 3-vinyl group of various chlorophyll (Chl) derivatives were examined. The reactions resemble thiol-olefin co-oxidation, except that the vinyl C = C double bond was cleaved to afford a formyl group without any transition metal catalyst, and that the simple anti-Markovnikov adduct of thiol to olefin was obtained as a minor product. Peripheral substituents of Chl derivatives little affected the reaction, while the central metal atom of the chlorin macrocycle influenced the composition of the products. Oxygen and acid dissolved in the reaction mixture can facilitate the oxidation. Sufficiently mild conditions in this regioselective oxidation at the C 31-position are significant in bioorganic chemistry.

Alternative synthesis of 3-acetyl, 3-epoxy, and 3-formyl chlorins from a 3-vinyl chlorin, methyl pyropheophorbide-a, via iodination

“…The mechanism of formylation of the vinyl group in Chl-d biosynthesis has not yet been clarified, while it is thought that co-oxidation of the vinyl group with thiol and oxygen plays a key role in the transformation. [4][5][6][7][8][9] Various (B)Chl derivatives are also derived in vitro from methyl pyropheophorbide-a (1), a stable synthetic intermediate prepared from abundant Chl-a, through transformation of the C3-vinyl group. Hydrobromination and subsequent hydrolysis of 1 afforded the C3-(1-hydroxy)ethyl derivative.…”