Complex-induced proximity effects: The effect of varying directing-group orientation on carbamate-directed lithiation reactions

A series of selected bicyclic carbamates in which the range of accessible a ngles and distances between the carbonyl group and the proton removed in an a-lithiation reaction are structurally defined have been investigated. Oxa zolidinones 7-10 undergo stereoselective lithiation-substitution reactions to provide cis-18-27 and cis-31-35 as the major diastereomers. Two series o f competition experiments show that the conformationally restricted carbama tes 7, 10, 11, and 15 undergo lithiation via complexes more efficiently tha n Boc amines 4-6. These results along with semiempirical calculations sugge st that a small dihedral angle and a calculated distance of 2.78 Angstrom b etween the carbamate carbonyl oxygen and the proton to be removed are favor able for a carbamate-directed lithiation. A series of tin-lithium exchange experiments on cis- and trans-18 and (S)-39 indicate that the configuration al stability of a carbamate-stabilized organolithium species may be enhance d by restrictive geometry.