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Directed Ruthenium‐Catalyzed C( sp 3 )H α‐Alkylation of Cyclic Amines Using Dioxolane‐Protected Alkenones
Author(s) -
Kulago Artem A.,
Van Steijvoort Ben F.,
Mitchell Emily A.,
Meerpoel Lieven,
Maes Bert U. W.
Publication year - 2014
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201400117
Subject(s) - chemistry , alkylation , piperidine , ruthenium , dioxolane , moiety , catalysis , ketone , amine gas treating , combinatorial chemistry , protecting group , organic chemistry , stereochemistry , alkyl
A catalytic system for ruthenium‐catalyzed C( sp 3 )H α‐alkylation of piperidines with dioxolane‐protected 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 α 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.