Directed Ruthenium‐Catalyzed C(sp3)H α‐Alkylation of Cyclic Amines Using Dioxolane‐Protected Alkenones. Issue 7 (7th May 2014)

• Record Type: Journal Article
• Authors: Kulago, Artem A.; Van Steijvoort, Ben F.; Mitchell, Emily A.; Meerpoel, Lieven; Maes, Bert U. W.
• Is Part Of: Advanced synthesis & catalysis. Volume 356:Issue 7(2014)
• Page Start: 1610
• Page End: 1618
• Publication Date: 2014-05-07
• Subjects: alkenes -- C(sp3)H activation -- directing groups -- piperidines -- ruthenium catalysis; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201400117
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: 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. Abstract :