Ring-closing C–O/C–O metathesis of ethers with primary aliphatic alcohols

Abstract

In canonical organic chemistry textbooks, the widely adopted mechanism for the classic transetherifications between ethers and alcohols starts with the activation of the ether in order to weaken the C–O bond, followed by the nucleophilic attack by the alcohol hydroxy group, resulting in a net C–O/O–H σ-bond metathesis. In this manuscript, our experimental and computational investigation of a Re2O7 mediated ring-closing transetherification challenges the fundamental tenets of the traditional transetherification mechanism. Instead of ether activation, the alternative activation of the hydroxy group followed by nucleophilic attack of ether is realized by commercially available Re2O7 through the formation of perrhenate ester intermediate in hexafluoroisopropanol (HFIP), which results in an unusual C–O/C–O σ-bond metathesis. Due to the preference for the activation of alcohol rather than ether, this intramolecular transetherification reaction is therefore suitable for substrates bearing multiple ether moieties, unparalleled by any previous methods.

Diastereoselective Reductive Etherification Via High-Throughput Experimentation: Access to Pharmaceutically Relevant Alkyl Ethers

“…They can be conveniently accessed via the classical Williamson ether synthesis, where an alkoxide anion attacks an alkyl electrophile to form the C–O bond under basic conditions. In addition, transition metal-mediated ether formations − and Mitsunobu reactions have been reported as reliable methods to access alkyl ethers. Recently, an electrochemical protocol to form hindered ethers has been disclosed, further demonstrating the long-standing interest in accessing structurally diverse ethers.…”

Transition-metal-free and additive-free intermolecular hydroarylation of alkenes with indoles in hexafluoroisopropanol

“…During the past ten years, there has been a significant surge in the use of HFIP as additives, cosolvents, or a part of ligands in chemical reactions, 9,10 due to its strong hydrogen-bond-donating ability, solvolysis ability, low nucleophilicity and cation-stabilization capacity. 11 Typically, additional transition metals or additives are required for cooperating with HFIP in activating carbonyl compounds, 12 epoxides, 13 alcohols, 14 halides 15 and unsaturated C–C bonds. 10 a–d ,16 Despite great advances in this field, green methodology merely using HFIP as a solvent or cosolvent to promote the reaction, i.e.…”

Late-Stage C–H Nitration of Unactivated Arenes by Fe(NO3)3·9H2O in Hexafluoroisopropanol

“…It has recently received ever-increasing attention from the scientific community as a result of its remarkable enhancing effects in catalysis , or its potential to act as a reaction promoter solely without the necessity for additional catalysis . As part of our continuing interests in HFIP-facilitated reactions and considering the recently established enhancing effects of HFIP on HNO 3 in electrophilic arene C–H nitrations, we speculate that the inherent nitrating capability of some metal nitrates might be further enhanced in HFIP to provide an operationally simple and generally applicable C–H nitration that synthetic organic chemists can easily resort to when such a transformation is in need, a protocol that can at least under most scenarios replace the “mixed acid” approach (Figure d).…”