Enantioselective cyclopropanation of carboxylic esters with alkyl magnesium bromides in the presence of titanium(IV) (4R,5R)-TADDOLates

The reaction of isopropyl 4-chlorobutyrate with 3 equiv of n-BuMgBr in the presence of 1 equiv of titanium(IV) (4R,5R)-TADDOLate in diethyl ether led to the formation of (1S,2S)-(3-chloropropyl)-2-ethylcyclopropanol in 55-70% yield and 55-65% ee. The reaction was performed in the presence of 20 mol % of the catalyst without significant loss in yield and enantioselectivity when solutions of the carboxylic ester and the Grignard reagent were added simultaneously at an equal rate to a refluxing solution of the titanium catalyst in ether. The cyclopropanation of isopropyl propionate under the same conditions gave (1S,2S)-1-ethyl-2-propylcyclopropanol in 50% yield and 65% ee. Its absolute configuration was determined by chemical correlation through acid-catalyzed isomerization to enantiomerically enriched (R)-(-)-4-methyl-3-heptanone, known as a minor component of the trail pheromone of ant Aphaenogaster albisetosus and enantiomer of the alarm pheromone of leaf-cutting ants Atta texana. (C) 2013 Elsevier Ltd. All rights reserved.