8‐Oxabicyclo[3.2.1]oct‐6‐en‐3‐ones: Application to the Asymmetric Synthesis of Polyoxygenated Building Blocks

Abstract

The development and design of reliable and efficient methods for the construction of chiral building blocks are crucial in modern natural product synthesis. 8-Oxabicyclo[3.2.1]oct-6-en-3-ones are readily accessible scaffolds with defined stereochemical features which have been exploited for non-aldol approaches to the preparation of chiral building blocks. Strategies for their enantioselective synthesis, including asymmetric cycloaddition methods, desymmetrization protocols, and "racemic switch operations", are presented and evaluated.

[4+3] Cycloadducts from Lewis Acid Mediated Reactions of Acroleins with Cyclopentadiene

“…The reported formation of 29aa and syn-diaxial 30bb from furan and enal 28 [9] is characteristic of a Wconfigured allyl cation equivalent and a compact/extended transition state in a direct [4+3] cycloaddition rather than the [2.2.1] oxabicyclic intermediate (Scheme 9). [10] It is of special interest that 5-norbornene-2-carbaldehyde derivatives that contain a quaternary center can be obtained in a stereocontrolled fashion. [11][12][13] In fact, the asymmetric synthesis of these aldehydes has become a benchmark for testing and inventing a host of new chiral Lewis acids.…”

Synthesis of 2,6-dioxatricyclo[3.3.1.03,7]nonanes by intramolecular haloetherification and/or transannular hydroxycyclization of alkenes in [4+3]-cycloadducts

“…The molecular illustrations (Figs. [3][4][5] were made by using the ORTEP-3 program. 30 The main X-ray data are quoted in Table 3.…”

“…Also, enantioselective versions of this type of reaction have been developed. 3 The intramolecular haloetherification and/or transannular cyclization deserves some comments about its precedents, many of them related with the reactivity and derivatization of [4þ3]-cycloadducts (Fig. 2).…”

“…Aside the 5-and 6-exo-trig cyclizations of alkenoxyl radicals that have been extensively used as a synthetic methodology of heterocycles, 4 whose stereoselectivity have been recently studied, 4l we consider here only the intramolecular transannular cyclizations mediated by ionic intermediates. This methodology has been used by Buchs and Ganter 5 as early as 1980 for the synthesis of the 2,6-dioxatricyclo[3.3.1.0 3,7 ]nonane core from 3-methyl-8-oxabicyclo[3.2.1]oct-6-en-3-ol and the 2,6-dioxatricyclo[3.3.2.0 3,7 ]decane core from 3-hydroxy-9-oxabicyclo[4.2.1]non-7-en-3-ol by reaction with Hg(OAc) 2 followed by NaBH 4 in order to prepare the new structure of dioxaisotwistane.…”

[4+3]‐Cycloaddukte aus der Lewis‐Säure‐vermittelten Reaktion von Acroleinen mit Cyclopentadien

“…So ist die Bildung von 29aa und dem syn-diaxialen 30bb aus Furan und dem Enal 28 [9] charakteristisch für ein W-konfiguriertes Allylkationen-¾quivalent und einen kompakten/gedehnten Übergangszu-stand in einer direkten [4+3]-Cycloaddition anstelle eines [2.2.1]-oxabicyclischen Zwischenstopps (Schema 9). [10] Es ist von besonderem Interesse, dass 5-Norbornencarbaldehyde mit einem quartären Kohlenstoffzentrum in stereokontrollierter Weise zugänglich sind. [11][12][13] Tatsächlich ist die asymmetrische Synthese dieser Aldehyde zu einer Testreaktion für die Untersuchung und Entwicklung einer Vielzahl verbesserter und verfeinerter chiraler Lewis-Säuren geworden.…”