Stereocontrol during the formation of 2-C mono-arylated pseudo-prolines byaromatic stacking interaction

When treated with anisaldehyde dimethylacetal the O-benzyl ester protected dipeptide Fmoc-NMeIle-Thr-OBzl (2, cf. Scheme 3), cyclizes to the 2-C(S) ep imer 3b assigned by NMR spectroscopy to chirality (R) at the 2-C position o f the resulting substituted 1,3-oxazolidine (Psi Pro) unit, while in the ac etalization of the corresponding O-methylester Fmoc-NMeIle-Thr-OMe (6),the 2-C(S) epimer 7a is predominantly formed stereoselectively and in quantitat ive yield. The course of the reaction can be rationalized by aromatic stack ing interactions involving the benzyl ester and aryl ether groups in a tran sition state close to a product structure of(R) chirality, whereas the lack of such interactions in the case of the methyl ester can be used to direct the acetalization towards the 2-C(S) epimer. (C) 1998 Elsevier Science Ltd . All rights reserved.