ACYCLIC STEREOSELECTION .52. ON THE MECHANISM OF LEWIS ACID MEDIATED NUCLEOPHILIC-SUBSTITUTION REACTIONS OF ACETALS

Lewis acid mediated nucleophilic substitution of acetals can occur by direct displacement (SN2) or oxocarbenium ion (SN1) mechanisms. With acyclic acetals, stereoselectivity increases with increasing steric bulk of the alkoxy group and with increasing polarity of the reaction medium. The enhanced stereoselectivity observed with acetals of secondary and tertiary alcohols is explained by perturbation of the approach trajectory of the nucleophilic alkene as it attacks the oxocarbenium ion. Highest stereoselectivity is seen in the reaction of 2-(l-phenyl-ethyl)-4,4,5,5-tetramethyl-l,3-dioxolane (4) with anal silane 5; only one diastereomeric product (9s) is obtained, even in the relatively nonpolar solvent CH2C12. The TiCl4-mediated reactions of cyclic acetals 18c, 18t, 25, and 28 with silyl enol ether 5 show that in these systems the substitution does not occur by the SN2 mechanism. © 1990, American Chemical Society. All rights reserved.