Addition–Hydroamination Reactions of Propargyl Cyanamides: Rapid Access to Highly Substituted 2‐Aminoimidazoles

Abstract

Ein wertvolles Pharmakophor, die 2‐Aminoimidazol‐Einheit, ist durch eine Reaktionssequenz aus Addition, Hydroaminierung und Isomerisierung mit vielfältigen Substitutionsmustern zugänglich (siehe Schema; R1,R4,R5=Alkyl; R3=Alkyl, Aryl; R2=H, Alkyl, Aryl). Die Synthese der Propargylcyanamid‐Vorstufen durch eine Dreikomponentenkupplung ermöglicht die Herstellung dieses wichtigen heterocyclischen Strukturmotivs in nur drei Stufen.magnified image

Concise and Diversity‐Oriented Route toward Polysubstituted 2‐Aminoimidazole Alkaloids and Their Analogues

“…A recently reported synthesis of polysubstituted 2-dialkylaminoimidazoles through the lanthanide-mediated hydroamination of propargylic cyanamides is rather limited by the diversity and availability of the starting electron-rich secondary benzylamines as well as by the harsh reaction conditions. [7] Accordingly, the development of straightforward and general procedures for the synthesis of diversely substituted 2-aminoimidazoles from readily available precursors is highly warranted. Herein, we report a rapid and highly efficient silver(I)-mediated synthesis of 1,4,5-trisubstituted 2-aminoimidazoles from secondary propargylamines.…”

Efficient Microwave‐Assisted Synthesis of Secondary Alkylpropargylamines by Using A3‐Coupling with Primary Aliphatic Amines

“…Primary amines are considered to be difficult substrates for A 3 -coupling reactions; this limits access to secondary propargylamines. [22] Nevertheless, secondary alkylpropargylamines are potent synthetic intermediates that have mainly been explored for the synthesis of pyrrolidin,…”

“…The lower yield can be attributed to the high reactivity of the resulting secondary propargylamine, which, as indicated by the mass spectrum of the reaction mixture, further reacts with aldehyde and acetylene to give a dimeric propargyl-A C H T U N G T R E N N U N G amine. [22] Therefore, modified reagent ratios and alternative Cu I catalysts were evaluated. The reaction was first run with 1.5 equivalents of amine, 1.0 equivalent of aldehyde and 3 equivalents of alkyne.…”

Regioselective Rhodium(II)‐Catalyzed Hydroaminations of Propargylguanidines

“…To this end we have been interested in the addition of guanidine NÀH bonds across CÀC p systems and recently reported a La III -catalyzed tandem addition-hydroamination reaction of propargylcyanamides which required forcing conditions, and resulted in exclusive 5-exo-dig cyclization. [4] This led us to study the hydroamination of preformed di-Boc protected propargylguanidines of the type 1, in hopes of finding a 6-endo-dig selective process. Traditionally, metalcatalyzed cyclizations on alkynes favor a 5-exo-dig pathway.…”

“…The sluggishness of the Au-catalyzed reactions directed our attention to Rh II . Dirhodium(II) carboxylates have rarely been used to activate alkynes, [14] however Murai et al have shown that [Rh 2 (tfa) 4 ] is a competent ene-ene-yne cycloisomerization catalyst and gives different product distributions than Pt II or Ru II . [15] Gratifyingly, [Rh 2 (tfa) 4 ] turned the selectivity over favoring the 6-endo product ( (Table 2) and it was immediately apparent that the reactivity of the dirhodium(II) carboxylates was quite unique.…”