The Grignard Reaction of Cyclodextrin-6-aldehydes Revisited: A Study of the Stereoselectivity Upon Addition of Organometallic Reagents to Aldehydes and Ketones

2(A-G), 3(A-G), 6(B-G)-Icosakis-O-benzyl-6(A)-O-oxo-beta-cyclodextrin was treated with aromatic and aliphatic Grignard reagents to give diastereomeric mixtures of the secondary alcohols with remarkable difference in polarity. Moderate-to-good yields and selectivity were obtained. By oxidizing the secondary alcohols, followed by a second Grignard reaction, good to excellent yields and selectivity of tertiary alcohols could be obtained. The stereochemistry of the reaction outcome was shown to be dependent on the order of addition of the Grignard reagents and could be efficiently controlled.