A protocol for the Pd-catalyzed C5(sp 3 )-H arylation of readily available 1-Boc-3-(picolinoylamino)piperidine with iodo-(hetero)arenes is reported. The substrate can be obtained from a biorenewable feedstock, namely L-arginine. The use of the right N1 protective group is decisive to get arylation. The addition of a catalytic amount of 2,6-dimethylbenzoic acid and performing the reaction at high concentration are important to achieve a high conversion and yield. The procedure gives arylated 1-Boc-3-(picolinoylamino)piperidines in a regiospecific (C5) and stereospecific (cis) manner. Orthogonal cleavage of the amide over the carbamate group allows one to further selectively derivatize the amino moieties of the piperidine scaffold.

A catalytic system for ruthenium-catalyzed CA C H T U N G T R E N N U N G (sp 3) À H a-alkylation of piperidines with dioxolaneprotected alkenones is reported. Dioxolane protection of the ketone proved crucial to obtain alkylation products. A diverse set of highly substituted piperidines was readily prepared in moderate to good yields via this methodology from easily accessible starting materials (C-2, C-3 and C-4 substituted piperidines). When the methodology is applied to C-3 substituted piperidines, featuring two a positions, only monoalkylated products (2,5-disubstituted) are observed. Even bicyclic amines, which feature a fused piperidine moiety, can be used. The successful directing group as well as protecting group (ketal) removal is also demonstrated. The methodology thus allows one to further derivatize and access hitherto unknown functionalized cyclic amine derivatives and will be useful in molecular library synthesis.

Directed Ruthenium-Catalyzed C(sp 3 )-H -Alkylation of Cyclic Amines Using Dioxolane-Protected Alkenones. -The pyridin-2-yl group is found to be an efficient directing group for the ruthenium catalyzed -alkylation of cyclic amines using dioxolane protected alkenones (II) and (XVII) or ester (XX). Even piperidines (XI) featuring two -positions give only 2,5-disubstituted products. In addition successful removal of the directing group as well as the protecting groups is demonstrated. -(KULAGO, A. A.; VAN STEIJVOORT, B. F.; MITCHELL, E. A.; MEERPOEL, L.; MAES*, B.