Synthesis of 3-aryl-3-pyridylallylamines related to zimelidine via palladium-catalyzed amination

Abstract

Reaction of aryl pyridyl ketones 1 with vinylmagnesium bromide followed by acetylation of the products 2 with acetic anhydride/EtgN and with 4-(dimethylamino)pyridine (DMAP) as a catalyst gave acetates 3 in high yields. Treatment of acetates 3 with dimethylamine in the presence of a palladium catalyst produced a mixture of E and Z isomers of 3-aryl-3-pyridylallylamines 4.

Palladium-catalysed reactions of alcohols. Part B: Formation of C–C and C–N bonds from unsaturated alcohols

“…The presence of these adducts was due to the in situ formation of isoprene (Scheme 11), which was effectively detected using a Peligot tube fitted to the top of the reflux condenser and containing a solution of bromine in CCl 4 . 128 (75) The teams of Bäckvall 129 …”

(E)‐,(Z)‐Parallel Preparative Methods for Stereodefined β,β‐Diaryl‐ and α,β‐Diaryl‐α,β‐unsaturated Esters: Application to the Stereocomplementary Concise Synthesis of Zimelidine

“…With this successful outcome (Methods A‐1, B‐1, C‐1, D ‐1) in our hands, we next envisaged an application for concise and parallel stereocontrolled synthesis of ( E )‐ and ( Z )‐ 3 . We referred fully to the pioneering works established by the groups of Bäckvall and Högberg 13. 14…”

“…The reported non‐stereoselective method13 for the synthesis of 3 involved the following reaction sequence: 1) addition of allylmagnesium chloride with p ‐bromophenyl 3‐pyridyl ketone, giving the tertiary allyl alcohol; 2) successive acid‐promoted allyl rearrangement, giving the allyl chloride; and 3) final dimethylamination. On the other hand, stereoselective synthesis14 was performed proficiently by a rigorous pH‐controlled reductive amination procedure.…”

Efficient synthesis of allylamines from a novel (E)-2,3-difunctionalized allyl bromide

“…It should be noted that the synthesis of allyl bromide 4 was always accompanied by the formation of its regioisomer 5, which was easily separable from the desired product 4 by silica gel column chromatography (Scheme 3). In order to establish a chemical library reserved for the various functionalized allylamines published during the last decade by our research group 30 and their use as basic skeletons of many biologically important substances [31][32][33][34][35][36][37] and numerous natural products [38][39][40][41][42][43][44][45][46][47] , we focused our attention on the synthesis of a new family of allylamines 6. The best reaction conditions were obtained following the reaction of the electrophilic allyl bromide (E)-4 with excess of monoalkylamines (2 equiv.)…”