New strategy for the synthesis of proaporphine and homoproaporphine-type alkaloids from a common intermediate

Abstract

Starting with 3-bromo-4,5-dimethoxybenzaldehyde 14, it was coupled with the boronic anhydride 15 using standard Suzuki reaction conditions to give 16 (91%). The aldehyde 16 was exposed to classical nitro-aldol reaction conditions to give 17 (88%), and conjugatively reduced with DIBAL-H to give 18 (91%). Protection of the amine 18 as its N-carbamate derivative 19, followed by condensation with glycol aldehyde dimer under acidic reaction conditions gave 20 (78%). Subsequent conversion of 20 into its mesylate derivative 21, and exposure to CsF under aprotic reaction conditions gave 22 (81%). Deprotection of 22 gave (±)-stepharine 10 in 29% overall yield though 8 steps. A similar sequence of reaction conditions converted the amine 18 into the -NTs protected homoproaporphine adduct 28.