Synthesis of functionalised isochromans: epoxides as aldehyde surrogates in hexafluoroisopropanol - Archive ouverte HAL
Article Dans Une Revue Chemical Science Année : 2023

Synthesis of functionalised isochromans: epoxides as aldehyde surrogates in hexafluoroisopropanol

Résumé

The oxa-Pictet–Spengler reaction is arguably the most straightforward and modular way to construct the privileged isochroman motif, but its scope is largely limited to benzaldehyde derivatives and to electron-rich β-phenylethanols that lack substitution along the aliphatic chain. Here we describe a variant of this reaction starting from an epoxide, rather than an aldehyde, that greatly expands the scope and rate of the reaction (<1 h, 20 °C). Besides facilitating the initial Meinwald rearrangement, the use of hexafluoroisopropanol (HFIP) as a solvent expands the electrophile scope to include partners equivalent to ketones, aliphatic aldehydes, and phenylacetyl aldehydes, and the nucleophile scope to include modestly electronically deactivated and highly substituted β-phenylethanols. The products could be easily further derivatised in the same pot by subsequent ring-opening, reductions, and intra- and intermolecular Friedel–Crafts reactions, also in HFIP. Finally, owing to the high pharmacological relevance of the isochroman motif, the synthesis of drug analogues was demonstrated.

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Autre
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Dates et versions

hal-04078006 , version 1 (21-04-2023)

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Cyprien Muller, Filip Horky, Marie Vayer, Andrei Golushko, David Lebœuf, et al.. Synthesis of functionalised isochromans: epoxides as aldehyde surrogates in hexafluoroisopropanol. Chemical Science, 2023, 14 (11), pp.2983-2989. ⟨10.1039/D2SC06692K⟩. ⟨hal-04078006⟩
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