An enantioselective total synthesis of (+)-atisirene by intramolecular double Michael reaction

Abstract

1,6-Conjugate addition of 2-methoxybenzylmagnesium bromide to 4-methylene-3,5,5-trimethylcyclo-hex-2-enone (7), followed by hydrocyanation, gave (±)-(1RS,2SR)-2-[2-(2-methoxyphenyl)ethyl]-1,3,3-trimethyl-5-oxocyclohexanecarbonitrile (9), which was converted into the (E)-α,β-unsaturated enone ester (22). Intramolecular double Michael reaction of compound (22) produced the A/B-cis tetracyclic compound (23) in 17% yield. On the other hand, Wieland–Miescher ketone(+)-(27) was selectively transformed into the (E)-α,β-unsaturated enone ester (46), whose intramolecular double Michael reaction furnished the A/B-trans compound (48) in 92% yield. (+)-15-Norisoatisirene (52), which had previously been transformed into (+)-atisirene (53), was synthesized from keto ester (48).