Efforts toward the Total Synthesis of Elisabethin A

Abstract

We describe our efforts toward the total synthesis of the natural product elisabethin A. The first route was guided by the proposed biosynthesis, assembling the 6,6-ring system before forming the five-membered ring including the quaternary carbon. The second approach includes a high yielding cyclization under Mitsunobu conditions as a key step. It allowed the preparation of an unusual and highly functionalized bicyclic 6,5-spiro compound. Both routes share a common advanced precursor obtained from an “underdeveloped” Claisen rearrangement of an aryl dienyl ether.

Crystal structures of two 1,2,3,4-tetrahydronaphthalenes obtained during efforts towards the total synthesis of elisabethin A

“…In our efforts towards the total synthesis of elisabethin A (Kaiser et al, 2022), many side and intermediate products were obtained (Kaiser, 2022). The syntheses and crystal structures of two of them, (2) and ( 8), are reported in this communication.…”

“…A 50 ml Schlenk flask was equipped with 111 mg (0.175 mmol, 1 equiv.) of compound (1) (Kaiser et al, 2022) dissolved in 15 ml of dry ethyl acetate. The colourless solution was Schlenked 10Â, then Pd/C (21 mg, 19 mmol, 11 mol%) was added.…”

Carpe diene! Europium-catalyzed [3,3] and [5,5] rearrangements of aryl-pentadienyl ethers

“…EuFOD, 21 PhMe, 110 °C) that allowed conversion of aryl-pentadienyl ethers 6a and 6b into the corresponding ortho migrated prochiral branched dienes 7a and 7b, respectively. 22 This [3,3] sigmatropic rearrangement could be conducted on multigram scale while obtaining high yields (Scheme 1, middle). Besides, the branched diene moiety proved to be of high synthetic value as a subsequent ring closing metathesis allowed the formation of bicyclic compound A as single diastereomer (former diene moiety in red).…”