Abstract
The acylation of the acetonitrile anion with lactones and esters in ethereal solvents was successfully exploited using inexpensive KOt-Bu to obtain a variety of β-ketonitriles and trifunctionalized building blocks, including useful O-unprotected diols. It was discovered that lactones react to produce the corresponding derivatized cyclic hemiketals. Furthermore, the addition of a catalytic amount of isopropanol, or 18-crown-6, was necessary to facilitate the reaction and to reduce side-product formation under ambient conditions.
Highlights
Introduction βKetonitriles represent highly versatile intermediates for the synthesis of heteroaromatic compounds and a wide variety of pharmaceuticals
When we applied Kim’s (KOt-Bu) method to δ-valerolactone, we obtained a highly viscous oil made up of a mixture of inseparable compounds that were unidentifiable by crude 1H NMR spectroscopy
To our delight, upon the addition of 20 mol % isopropanol (IPA) to the THF reaction mixture, we obtained a moderate amount of the desired product, albeit not as the open-chain β-ketonitrile 2, but exclusively as the corresponding, cyclized hemiketal 5 (Scheme 2)
Summary
Introduction βKetonitriles represent highly versatile intermediates for the synthesis of heteroaromatic compounds and a wide variety of pharmaceuticals. When we applied Kim’s (KOt-Bu) method to δ-valerolactone, we obtained a highly viscous oil made up of a mixture of inseparable compounds that were unidentifiable by crude 1H NMR spectroscopy (see Supporting Information File 1). To our delight, upon the addition of 20 mol % isopropanol (IPA) to the THF reaction mixture, we obtained a moderate amount of the desired product, albeit not as the open-chain β-ketonitrile 2, but exclusively as the corresponding, cyclized hemiketal 5 (Scheme 2).
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