Tetrahedron Letters,Vol.28,No.l8,pp 2013-2016,1987 oo40-4039/87 $3.00 + .OO Printed in Great Britain Pergamon Journals Ltd. ULTRASOUND IN ORGANIC SYNTHESIS lll. RETENTION OF OPTICAL ACTIVITY IN BABBIER REACTIONS FROM S(+) 2-OCTYL HALIDES. MECHANISTIC CONSEQUENCES Jayne C. de Souza-Barboza,Jean-Louis Luche*, Christian PBtrier Laboratoire d'Etudes Dynamiques et Structurales de la Selectivite LEDSS BBt. 52 - Universite Scientifique,Technique et MBdicale de Grenoble B.P. 68 38402 St Martin d'Heres Cedex, France Abstract : S(t) 2-octyl halides react spontaneously or under sonication with lithium and cyclohexanone to give an optically active alcohol. Its enantiomeric excess and absolute configuration,strongly suggest the existence of 2 reactive intermediates following different stereochemicalpathways to the condensationalcohol. Except for a limited number of particular cases2, organic halides in which the halogen atom is bond to a single asymmetric carbon react with metals with complete loss of stereochemicalintegrity3. In contrast, we report here that an optical activity is preserved when the Barbier procedure is followed, especially under ultrasonic irradiation. From these results, a more accurate picture of this complex reaction can be formulated4. Experiments, listed in Table 1, were conducted with S(+) 2-octyl halides 1, lithium metal and cyclohexanone (Scheme 1) and optically active alcohols 2 were obtained in every case. The stereochemical parameters, i.e. the absolute configuration and enantiomeric excesses (e.e.) of 2 were determined chemically according to Levene zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM 7 . ([a],-6.5”T e.e. 8 Methyl R(-) 2-methyl octanoate 3 30% ) was reacted with 1,5-dibromopentane and lithium in THF (-2s°C, 35 min sonication) to give R(+)Z([a]D + loo) in 57% yield". Recovered ester 3 showed no loss of optical activity. The annelation process applied to methyl (+)2-deutero-2-methyl-octanoate (94 -- + 3% D at C2 11) gave (+)2 in 62% yield with 90 + 3% deuterium at C2, i.e. 96 + 3% label -- conservation. It can thus be assumed that annelation of 3 to 2 occurs with at least 96% retention of configuration.The rotation of enantiomericallypure 2 should then be [a]D 34 z 2O, a value which was used for the stereochemical evaluation of the Barbier reactions. The origin of the optical activity in compound 2 can be discussed in the following terms. A "chiral .solvent"effect seems highly improbable. Under the conditions of run 7 [ X=Br, O°C, 30 min, sonication at 16OV], the reaction was effected with a slow addition of the optically active halide to keep its concentration at a minimum level. No significant difference in the e.e.s (12% instead of 10%) of 2 resulted in comparison to the usual procedure. Thus, the optical activity of 2 must find its origin in a stereoselective reaction pathway. Optically active 2-octyl lithium was obtained in poor yield by low temperature (-80oC) halogen lithium exchange from S(+) Z-octyl iodide and (+) s, butyl lithium12. Addition of cyclohexanone to the mixture gave S(-) 2 (3% yield, [aID- 7O, e.e. 21%) with retention of configurationat the original chiral center. Thus the predominant R (+) 2 enantiomer obtained 2013