Unexpected Thorpe Reaction of an α-Alkoxynitrile 英文参考文献.docVIP

Molecules 2000, 5, 127-131 molecules ISSN 1420-3049 Unexpected Thorpe Reaction of an α-Alkoxynitrile Lajos Kovács Department of Medicinal Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary Tel.: +36 62 54 51 45, Fax: +36 62 42 52 62, E-mail: kovacs@ovrisc.mdche.u-szeged.hu, URL: http://www.mdche.u-szeged.hu/staff/kovacs.htm Received: 19 January 2000 / Accepted: 14 February 2000 / Published: 17 February 2000 Abstract: α-Alkoxynitrile 1 in the presence of tris(methylthio)methyllithium 2 at –78oC gave the dimer 5 instead of the expected C1-elongated product 3. The formation of com- pound 5 is explained in terms of anion formation and self-condensation, a variant of the Thorpe reaction. Scrutinizing the 1H NMR spectra revealed that the enamine tautomer 5b is predominant over the imine 5a in the solvents investigated. Keywords: Thorpe reaction, self-condensation. Introduction Nitrile 1 (Scheme 1) was obtained en route to acyclic analogues of the C-nucleoside tiazofurin [1]. This compound was deemed to be a good starting material for the synthesis of α-keto ester 4 via in- termediate 3. This assumption was based on analogy with the Grignard reaction of nitriles giving rise to ketones [2] or the Blaise reaction (Reformatsky reaction of nitriles affording β-keto esters) [3]. For the required carboxylate anion synthon different tris(alkylthio or arylthio)methyllithiums, de- rived from tris(alkyl or arylthio)methanes [4], were used successfully in the C1 elongation of ketones [5] and lactones [6]. Most often [tris(methylthio)methyl]lithium (2) was applied which is stable up to –40oC [7]. The obtained trithioorthoesters can be transformed into the corresponding esters using the common mercury(II) salt-assisted demercaptalisation procedure. In principle, alkyl chloroformates could also be employed as C1 synthons. However, in the single reported Reformatsky-type reaction of ethyl chlorofo