A Mild, Efficient and Sustainable Tetrahydropyranylation of Alcohols Promoted by Acidic Natural Deep Eutectic Solvents

Abstract

A straightforward protocol to promote the tetrahydropyranylation of alcohols, using for the first time bioinspired acidic natural deep eutectic solvents (NADESs) as non‐innocent reaction media under mild reaction conditions, was reported. This approach enables the preparation of several tetrahydropyranyl (THP) ethers starting from primary, secondary and tertiary alcohols in short reaction times and with high levels of chemoselectivity, working under air and without the need of additional catalyst. The sustainability of the methodology was further highlighted by its scalability and the easy recyclability of the NADES, allowing multigram preparations of THP ethers without any loss of the catalytic activity of the reaction media up to ten recycling steps. Telescoped, one‐pot tetrahydropyranylation/nucleophilic acyl substitution transformations using the same eutectic mixture were also demonstrated.

A Review on the Use of Deep Eutectic Solvents in Protection Reactions

“…Blangetti et al presented a study showing that acidic natural deep eutectic solvents (NADESs) are effective in catalyzing the tetrahydropyranylation of alcohols under mild conditions. This method enables the synthesis of tetrahydropyranyl (THP) ethers from various types of alcohols quickly, with easy isolation using the eco-friendly solvent cyclopentyl methyl ether (CPME) [ 52 ]. Remarkably, the reaction maintains excellent selectivity in the presence of competing hydroxy groups and can accommodate acid-sensitive functional groups.…”

Efficient and Low‐Impact Acetalization Reactions in Deep Eutectic Solvents

“…developed acetalization processes of aliphatic and aromatic carbonyls with diols employing ammonium salts as acidic catalysts, either under homogeneous [19] or heterogeneous catalysis [20] . Lastly, Deep Eutectic Solvents were used to convert monosaccharides and methyl glycosides in mono‐ and di‐ O ‐isopropylidene derivatives, [21] and alcohols in THP (tetrahydropyranyl) derivatives, respectively [22] . However, despite the many reports found in the literature, most of them suffer from several drawbacks such as poor chemoselectivity and atom‐economy, need of drying agents, high reaction temperatures, stoichiometric amounts of acids and limited scope of substrates thus limiting the application of acetalization in chemical synthesis.…”

“…[20] Lastly, Deep Eutectic Solvents were used to convert monosaccharides and methyl glycosides in mono-and di-O-isopropylidene derivatives, [21] and alcohols in THP (tetrahydropyranyl) derivatives, respectively. [22] However, despite the many reports found in the literature, most of them suffer from several drawbacks such as poor chemoselectivity and atom-economy, need of drying agents, high reaction temperatures, stoichiometric amounts of acids and limited scope of substrates thus limiting the application of acetalization in chemical synthesis. Moreover, the preparation of acetals is commonly achieved in solvents such as acetonitrile, THF, benzene, toluene and DMF leading to complex product recovery and isolation procedures.…”

“…In this context, we became recently interested in the use of DESs either as solvents [23] or non-innocent solvents in organic synthesis. [22,24] DES are generally defined as mixtures composed by an HDB (Hydrogen Bond Donor) and an HBA (Hydrogen Bond Acceptor). The supramolecular structure of these mixtures, characterized by an extensive hydrogen bonding pattern, [25] impacts on the reactivity of common reagents and often provides an unexpected reactivity to traditional synthetic transformations.…”

“…In this context, we became recently interested in the use of DESs either as solvents [23] or non‐innocent solvents in organic synthesis [22,24] . DES are generally defined as mixtures composed by an HDB (Hydrogen Bond Donor) and an HBA (Hydrogen Bond Acceptor).…”