Issue 2, 2019

Reversibility and reactivity in an acid catalyzed cyclocondensation to give furanochromanes – a reaction at the ‘oxonium-Prins’ vs.ortho-quinone methide cycloaddition’ mechanistic nexus

Abstract

Herein we report a combined experimental and computational investigation of the acid catalyzed cyclocondensation reaction between styrenyl homoallylic alcohols and salicylaldehyde to form furanochromanes. We disclose a previously unreported isomerisation of the ‘unnatural’ trans-fused products to the diastereomeric ‘natural’ cis-fused congeners. Notwithstanding the appeal of assuming this corresponds to endo to exo isomerisation of Diels–Alder (D–A) adducts via concerted retro-cycloaddition/cycloaddition reactions of an in situ generated ortho-quinone methide with the styrenyl alkene, our combined Hammett/DFT study reveals a stepwise Prins-like process via discrete benzylic carbocation intermediates for all but the most electron deficient styrenes. As these reactions fortuitously lie at the intersection of these two mechanistic manifolds, it allows us to propose an experimentally determined indicative ρ+ value of ca. −3 as marking this nexus between a stepwise Prins-type pathway and a concerted cycloaddition reaction. This value should prove useful for categorising other reactions formally involving ‘ortho-quinomethides’, without the need for the extensive computation performed here. Logical optimisation of the reaction based upon the mechanistic insight led to the use of HFIP as an additive which enables exclusive formation of ‘natural’ cis-fused products with a ∼100-fold reaction rate increase and improved scope.

Graphical abstract: Reversibility and reactivity in an acid catalyzed cyclocondensation to give furanochromanes – a reaction at the ‘oxonium-Prins’ vs. ‘ortho-quinone methide cycloaddition’ mechanistic nexus

Supplementary files

Article information

Article type
Edge Article
Submitted
27 Sep 2018
Accepted
18 Oct 2018
First published
19 Oct 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 406-412

Reversibility and reactivity in an acid catalyzed cyclocondensation to give furanochromanes – a reaction at the ‘oxonium-Prins’ vs.ortho-quinone methide cycloaddition’ mechanistic nexus

C. D.-T. Nielsen, W. J. Mooij, D. Sale, H. S. Rzepa, J. Burés and A. C. Spivey, Chem. Sci., 2019, 10, 406 DOI: 10.1039/C8SC04302G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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