Unexpected Thorpe Reaction of an α-Alkoxynitrile

Abstract

α-Alkoxynitrile 1 in the presence of tris(methylthio)methyllithium 2 at -78ºC gave the dimer 5 instead of the expected C 1 -elongated product 3. The formation of compound 5 is explained in terms of anion formation and self-condensation, a variant of the Thorpe reaction. Scrutinizing the 1 H NMR spectra revealed that the enamine tautomer 5b is predominant over the imine 5a in the solvents investigated.

Cytosine Analogues from Substituted Acetonitriles via Thorpe Condensation

“…Examination of the spectral data revealed that the product was an oxygenated β-enaminonitrile (general structure 2 ) arising via a Thorpe condensation (see Table ) . The facile intermolecular dimerization of cyanomethyl aryl ethers at low temperature was surprising, as Thorpe condensations of alkyl nitriles require elevated temperatures and prolonged reaction times. , The literature provides few examples of the Thorpe condensation of cyanomethyl ethers, and these are primarily examples of undesired side products that were isolated in poor yield. , Recognizing that β-enaminonitriles 2 could function as a scaffold for the construction of highly functionalized cytosine derivatives, we subjected a range of α-aryloxyacetontriles to our reaction conditions (Table ). These condensations afford excellent yields for a wide range of aryl ethers, including sterically hindered cases such as ortho -substituted aryl ethers 1b , d − f .…”