Total Syntheses of (+)‐Aquatolide and Related Humulanolides

Abstract

The short, efficient total synthesis of (+ +)-aquatolide was achieved by ab iomimetic transannular [2+ +2] photocycloaddition, and provides the first example of constructing a5 /5/4/8-ring system from asteriscunolides.F urthermore,t he reaction leading to a5 /4/4/7-ring system, the originally proposed structure of aquatolide,w as also developed. This strategy achieved syntheses of five more humulanolides,( À)asteriscunolides A, C, D, and I, and (+ +)-tetradehydroasteriscanolide.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201904404. Angewandte ChemieZuschriften Scheme 1. Construction of the asteriscunolide skeleton. DDQ = 2,3dichloro-5,6-dicyano-1,4-benzoquinone, DMSO = dimethylsulfoxide, LiHMDS = lithium bis(trimethylsilyl)amide, MPM = 4-methoxyphenylmethyl, THF = tetrahydrofuran.

Recent advances in the total synthesis of cyclobutane-containing natural products

“…In 2019, Takao and coworkers reported a concise total synthesis of (+)-aquatolide (111) by a biomimetic transannular [2 + 2] photocycloaddition to build up its cyclobutane subunit at the late stage (Scheme 16). 47 Their synthesis commenced with vinyl iodide 103, which was readily prepared from known alcohol 101 in 76% yield over four steps. The subsequent ring-opening/ringclosing/cross-metathesis (ROM/RCM/CM) reaction of 103 proceeded in a cascade manner to produce the desired aldehyde.…”

Lessons in Strain and Stability: Enantioselective Synthesis of (+)‐[5]‐Ladderanoic Acid

“…Initial investigations revealed that a productive reaction occurred to generate what was originally thought to be the desired [5]‐ladderane 26 with good yield and enantioselectivity when the oxazaborolidene 25 was used. However, upon rigorous structural determination by X‐ray crystallography of a derivative ( 30 ), it was revealed that the [2.1.1]‐bicycle 27 was formed as the exclusive product! This remarkable transformation is proposed to occur by initial [2+2] cycloaddition to generate the desired cycloadduct 26 as outlined in Scheme . However, because of the inherent ring strain, a retro‐[2+2] cycloaddition occurs rapidly to generate the chiral allenoate 28 .…”

“…However,u pon rigorous structural determination by X-ray crystallography of ad erivative (30), it was revealed that the [2.1.1]-bicycle 27 was formed as the exclusive product! [11,12] This remarkable transformation is proposed to occur by initial [2+ +2] cycloaddition to generate the desired cycloadduct 26 as outlined in Scheme 5. However, because of the inherent ring strain, ar etro-[2+ +2] cycloaddition occurs rapidly to generate the chiral allenoate 28.U pon C À Cb ond rotation and crossed-[2+ +2] cycloaddition (via 29), the observed product 27 could be formed.…”

A Volumetric Analysis of the 1H NMR Chemical Shielding in Supramolecular Systems

“…Aquatolide (C 15 H 18 O 3 ) was a subject of numerous structural investigations (see the most recent study [21] and work cited therein, and also references [22][23][24]). Based on the { 1 H, 13 C} chemical shifts taken from Supplementary Table S3 of reference [24], which were measured in DMSO (dimethyl sulfoxide), the corresponding HETCOR spectrum was simulated by the aforementioned computational approach, of course using DMSO as an implicit solvent in the PCM method.…”