Pergamon Tetrahedron Letters, Vol. 38, No. 10, pp. 181%1820, 1997 O 1997 Elsevier Science lad All rights reserved.Printed in Great Britain. PII: S0040-4039(97)00159-7 0040-4039/97 $17.00 + 0.00 Chemoselective Addition of Grignard Reagents to Aikoxycarbonylalkyl- N-imidazolium-N-methyl Amides: Synthesis of 4-Oxo and Homologous Esters Maria A. de las Heras, Juan J. Vaquero, Jos~ L. Garcia-Navio, Julio Alvarez-Builla* Departamento de QuimicaOrganica, Universidadde Alcalfi, 2887 l-Alcal~i de Henares, Madrid. Spain. Abstract: A method for the synthesis of 4-oxo and homologous esters is achieved by metalation of alkoxycarbonylalkyl-N-imidazolium-N-methyl amideswith Iequiv of LDA followed by highlyehemoseleetive addition of 1 equiv ofa Grignard reagent. © 1997 Elsevier Science Ltd. All fights reserved. Although it has been known for a long time that the carbonyi group can be formed by reacting organometallics with carboxylic acid derivatives,1 only with the development of selective acylating reagents 2 (e.g. Weinreb's amide 3'4) has this reaction proved to be of synthetic utility. Recently, we demonstrated that N-imidazolium-N- methylamides I and bis-amides 2 behave as highly selective acylating reagents towards organometallics leading in good to excellent yields to ketones 5 and diketones. Moreover, the 1-(N-alkoxyoxalyl-N-methylamino)-3- methylimidazolium salts 3 were shown to yield 2-oxo esters by addition of Grignard reagents 7 whereas in the case of the equivalent Weinreb type amide 4 the addition of an aliphatic organometallic takes place on the ester group leading to undesired 2-oxo amides 8 (Scheme 1). Me,, N O /'~ + " ~.,- N .. N ..JL. R _ o × , N EIF Me R... OEt R1-M Me 1 Me Me O / "~N'N" "y" "N "N'~ R 1= Aliphatic X- Me IVle X- a=Li, agX Me o 3R= ~N*= R'%OEt O 4: R = OMe O R--.N%RI Me O Scheme 1 1817