Water opens the door to organolithiums and Grignard reagents: exploring and comparing the reactivity of highly polar organometallic compounds in unconventional reaction media towards the synthesis of tetrahydrofurans† ‡

Abstract

Grignard and organolithium reagents undergo smooth nucleophilic additions to γ-chloroketones “on water”.

Abstract

It has always been a firm conviction of the scientific community that the employment of both anhydrous conditions and water-free reaction media is required for the successful handling of organometallic compounds with highly polarised metal–carbon bonds. Herein, we describe how, under heterogeneous conditions, Grignard and organolithium reagents can smoothly undergo nucleophilic additions to γ-chloroketones, on the way to 2,2-disubstituted tetrahydrofurans, “on water”, competitively with protonolysis, under batch conditions, at room temperature and under air. The reactivity of the above organometallic reagents has also been investigated in conventional anhydrous organic solvents and in bio-based eutectic and low melting mixtures for comparison. The scope and limitations of this kind of reaction are discussed.

Notes

†Dedicated to Professor Paul Knochel on the occasion of his 60 ^th birthday.

‡Electronic supplementary information (ESI) available: Experimental procedures, spectroscopic data of compounds 2a, 2c, 3a–n, and 4a, and copies of ¹H and ¹³C NMR spectra of compounds 2a, 2c, 3h, 3i, and 3m. See DOI: 10.1039/c5sc03436a