Lewis Acid Catalyzed (4π+2σ) Annulation of Bicyclobutanes with Dienol Ethers for the Synthesis of Bicyclo[4.1.1]octanes

16 April 2024, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Bicyclic carbocycles containing a high fraction of Csp3 have become highly attractive synthetic targets because of the multiple applications they have found in medicinal chemistry. The formal cycloaddition of bicyclobutanes (BCB) with two- or three- atom partners has recently been extensively explored for the construction of bicyclohexanes and bicycloheptanes, but applications to the synthesis of medium-sized bridged carbocycles remained more limited. We report herein the formal (4π+2σ) cycloaddition of BCB ketones with silyl dienol ethers. The reaction occurred in the presence of 5 mol% aluminium triflate as a Lewis acid catalyst. Upon acidic hydrolysis of the enol ether intermediates, rigid bicyclo[4.1.1]octanes (BCOs) diketones could be accessed in up to quantitative yields. This procedure tolerated a range of both aromatic and aliphatic substituents on both the BCB substrates and the dienes. The obtained BCO products could be functionalized through reduction and cross-coupling reactions.

Keywords

Bicyclobutanes
Bicyclooctanes
Dienol silyl ethers
Annulation reactions
Lewis acid catalysis

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
experimental procedures, compound characterization, X-ray data and NMR spectra of new compounds
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.