The first enantioselective total syntheses of (À)pallambins A-D have been achieved in 15 or 16 steps from aknownchiral cyclohexenone.Salient features of the syntheses include ap alladium-catalyzed oxidative cyclization to assemble the [3.2.1]bicyclic moiety,a nE schenmoser-Claisen rearrangement/lactone formation sequence to construct the Cring, an intramolecular Wittig reaction to form the Dring, and individual transformations of pallambins Cand Dtogenerate pallambins Aa nd B. The described synthesis avoids protecting-group manipulations through the design of highly chemoand stereoselective transformations.D uring the course of this work, ap alladium-catalyzed method for the dehydrobromination of a-bromoketones was developed, and the scope of this transformation was also investigated.

The first enantioselective total syntheses of (−)‐pallambins A–D have been achieved in 15 or 16 steps from a known chiral cyclohexenone. Salient features of the syntheses include a palladium‐catalyzed oxidative cyclization to assemble the [3.2.1]bicyclic moiety, an Eschenmoser–Claisen rearrangement/lactone formation sequence to construct the C ring, an intramolecular Wittig reaction to form the D ring, and individual transformations of pallambins C and D to generate pallambins A and B. The described synthesis avoids protecting‐group manipulations through the design of highly chemo‐ and stereoselective transformations. During the course of this work, a palladium‐catalyzed method for the dehydrobromination of α‐bromoketones was developed, and the scope of this transformation was also investigated.

Main observation and conclusion A full account of the total synthesis of (–)‐pallambins A—D (1—6) is described. The strategy was devised by simulating their biosynthetic pathway. The left‐part bicyclo[3.2.1]octane system of pallambins C and D was efficiently constructed via a palladium‐ catalyzed oxidative cyclization. For construction of the right‐part tetrahydrofuran/γ‐lactone moiety (C/D rings), initial attempts to synthesize the allylic alcohol 15 for an one‐step Pd‐mediated alkoxycarbonylation have failed. However, during the course of this work, an unprecedented CH3Li‐mediated method for conversion of bromoisoxazoline to the corresponding β‐hydroxy nitrile has been discovered. Furthermore, a stepwise protocol was designed, namely an Eschenmoser‐Claisen rearrangement/Lactonization to generate the C ring, and a non‐classical Wittig reaction to form the D ring. During the course of this work, a palladium‐catalyzed method for dehydrobromination of bromide ketone was developed. Finally, an individual transformation of pallambins C (3) and D (4) generated pallambins A (5) and B (6) under mild UV irradiation. Thus, the first enantioselective total syntheses of (–)‐pallambins A—D have been achieved in 15 or 16 steps from the known chiral cyclohexenone 8. The described synthesis avoids protecting‐group manipulations by designing highly chemo‐ and stereoselective transformations.