11-Step Total Synthesis of Pallambins C and D

Abstract

The structurally intriguing terpenes pallambins C and D have been assembled in only 11 steps from a cheap commodity chemical: furfuryl alcohol. This synthesis, which features a redox-economic approach free of protecting-group manipulations, assembles all four-ring systems via a sequential cyclization strategy. Of these four-ring constructing operations, two are classical (Robinson annulation and Mukaiyama aldol) and two are newly devised. During the course of this work a method for the difunctionalization of enol ethers was developed, and the scope of this transformation was explored.

Enantioselective Total Syntheses of Pallambins A–D

“…The unprecedented and challenging molecular architectures of 1 – 6 have attracted considerable attention from synthetic chemists . Wong and co‐workers pioneered the first total synthesis of (±)‐ 1 and (±)‐ 2 , (±)‐ 3 and (±)‐ 4 in a biomimetic manner from the racemic Wieland–Miescher ketone .…”

Enantioselective Total Syntheses of Pallambins A–D

“…[7] In 2016, the Baran group reported an elegant approach to 3 and 4 without any protecting-group manipulations. [8] Encouraged by our recent success in the total synthesis of 1 and 2 from 8 and the aforementioned biogenetic hypothesis, we envisioned that cyclohexenone 8 could serve as acommon intermediate (corresponding to 7)f or the synthesis of 1-6 Figure 1B). We should thus be able to achieve the divergent synthesis of 1-6 in ab ioinspired manner.…”

“…Cleavage of the C7ÀC8 bond of the labdane-type diterpenoid provides the common precursor 7. [4][5][6][7][8] Wong and co-workers pioneered the first total synthesis of (AE)-1 and (AE)-2,( AE)-3 and (AE)-4 in ab iomimetic manner from the racemic Wieland-Miescher ketone. Pallambins C( 3)a nd D( 4)a re formed through demethylation followed by C4ÀC8 bond reconstruction.…”

“…[2c] Theu nprecedented and challenging molecular architectures of 1-6 have attracted considerable attention from synthetic chemists. [8] Encouraged by our recent success in the total synthesis of 1 and 2 from 8 and the aforementioned biogenetic hypothesis, we envisioned that cyclohexenone 8 could serve as acommon intermediate (corresponding to 7)f or the synthesis of 1-6 Figure 1B). [5a,b] Carreira and Ebner reported the first total syntheses of (AE)-pallambins A( 5)a nd B( 6)b yt he use of pentafulvene in an unprecedented Diels-Alder reaction in 2015.…”

“…[2c] Theu nprecedented and challenging molecular architectures of 1-6 have attracted considerable attention from synthetic chemists. [4][5][6][7][8] Wong and co-workers pioneered the first total synthesis of (AE)-1 and (AE)-2,( AE)-3 and (AE)-4 in ab iomimetic manner from the racemic Wieland-Miescher ketone. [5a,b] Carreira and Ebner reported the first total syntheses of (AE)-pallambins A( 5)a nd B( 6)b yt he use of pentafulvene in an unprecedented Diels-Alder reaction in 2015.…”