~ ) Pergamon Tetrahedron: Asymmetry, Vol.8, No. 14, pp. 2479-2496, 1997 © 1997 ElsevierScience Ltd. All rights reserved. Printed in GreatBritain PII: S0957-4166(9"/)00272-3 0957-4166/97 $17.00 + 0.00 Camphorsulfonamide derivatives: a new class of chiral catalysts for the titanium alkoxide-promoted addition of dialkylzinc to aldehydes Diego J. Ram6n and Miguel Yus * Departamento de Qufmica Org~ica, Facultad de Ciencias, Universidad de Alicante, Aptdo. 99, E-03080 Alicante, Spain Abstract: The enantioselective addition of dialkylzinc to several aldehydes, using different chiral bidentate ligands (3a-j, 4a-h) [derived from (+)-10-camphorsulfonyl chloride] and titanium alkoxide as catalysts, is studied. The influence of temperature, titanium alkoxide, stoichiometry, additive, aldehyde and ligand structure is also studied. © 1997 Elsevier Science Ltd Introduction Catalytic asymmetric synthesis I is a valuable method for preparing optically active substances. In contrast to stoichiometric methods, the chiral information of a ligand molecule is transferred to several product molecules, through a catalytic cycle; in addition, the reactivity of the active species bearing the chiral ligand is, in general, enhanced, compared to that of the non-chiral ligand, due to the so-called "ligand acceleration effect". 2 Among the enantioselective catalytic transformations, those involving carbon-carbon bond formation are probably the most attractive for synthesis, compared to functional group conversions on a given carbon skeleton) Concerning this subject, the stereoselective addition of organometallics to one of the two heterotopic faces of a carbonyl group has been extensively studied, particularly, the addition of diethylzinc to benzaldehyde has become a prototype in the evaluation of new chiral catalysts. R' NH //J~N/R 'NH OH I t SO2OF ~ R LSO2.~R I II III (X = O, S) R' IV Originally, 4 dialkylzinc was activated to react with aldehydes by the addition of chiral 1,2-, 1,3- and 1,4-diols, aminoalcohols and diamines. 5 In these cases, several studies indicated that dimeric zinc complexes, containing the chiral ligands, act both as Lewis acid for carbonyl activation and as the origin from which the nucleophilic group was transferred. 5a'6 This fact introduced the idea of using a chiral Lewis acid for carbonyl activation, such as oxazaborolidines 7 and titanates. 8 In the case * Corresponding author. Fax: +34-6-5903549; Email: yus@ua.es 2479