Tuning the Reactivity of Isocyano Group: Synthesis of Imidazoles and Imidazoliums from Propargylamines and Isonitriles in the Presence of Multiple Catalysts

Abstract

The reaction of propargyl amines with tert-butylisonitrile in the presence of a catalytic amount of both Yb(OTf)3 and AgOTf afforded imidazoles, whereas the same reaction with primary and secondary alkylisonitriles, as well as arylisonitriles, in the presence of three metal salts [Yb(OTf)3/AgOTf/KOTf] resulted in the 1,3,4,5-tetrasubstituted imidazoliums in excellent yields. Both chiral amines and chiral isonitriles can be used to provide corresponding chiral heterocycles without racemization. In this multiple catalytic system, Yb(OTf)3 catalyzed the insertion of isonitriles to the N-H bond of amines, AgOTf catalyzed the 5-exo-dig cyclization of the resulting amidine nitrogen to the tethered triple bond, and KOTf promoted the salt metathesis, thus providing at the same time the counterion to the imidazolium. Against common knowledge, the isocyano group acted in these reactions as a polarized triple bond instead of conventional carbene-like function.

Modular Access to Tetrasubstituted Imidazolium Salts through Acid‐Catalyzed Addition of Isocyanides to Propargylamines

“…double catalysis of Ag + /Yb 3+ cations, [10] prompted us to disclose our findings. In this way, we prepared A 3 adducts, [11] arising from the metal-catalyzed interaction of, a primary amine 1, an aldehyde 2 and a terminal alkyne 3, to afford propargylamines 4 (Scheme 1).…”

Switchable [3+2] and [4+2] Heteroannulation of Primary Propargylamines with Isonitriles to Imidazoles and 1,6‐Dihydropyrimidines: Catalyst Loading Enabled Reaction Divergence

“…With this idea in mind, propargylamine 15 a and tert ‐butylisonitrile ( 1 a ) were chosen as test substrates for the survey of reaction conditions (Table ). While no reaction occurred under thermal conditions (Table , entry 1), heating a solution of 1 a and 15 a in xylenes at 90 °C in the presence of ytterbium triflate (Yb(OTf) 3 , (0.2 equiv)) afforded the NH insertion product 19 a (entry 2) . Increasing the reaction temperature to 120 °C provided cleanly imidazole 16 a and 1,6‐dihydropyrimidine 17 a in a one‐to‐one ratio (entry 3).…”

“…Indeed, we have very recently reported a synthesis of imidazolium 14 in which the isocyano group acted formally as a polarized triple bond, hence as a two‐atom synthon, to undergo formal [3+2] cycloaddition with secondary propargylamines 13 (Eq. (3), Scheme ) . In this multicatalytic process, three task‐specific metal salts acted cooperatively to channel the reaction towards the formation of 1,3,4,5‐tetrasubstituted imidazolium salts 14 .…”

Silver‐Catalyzed Cross‐Coupling of Isocyanides and Active Methylene Compounds by a Radical Process

“…F urthermore,t he yield of 5a was sharply decreased to 23 %( when the reaction was run under an N 2 atmosphere), thus confirming the participation of oxygen in the reaction. Theo xidant behavior of Ag 2 CO 3 was explained by the often observed silver mirror in the reactions.M eanwhile,t he complex Ag 2 CO 3 (RNC) n may be formed [27] and react with A to give the imidoyl radical B. Based on the results from the experimental investigations and related literature precedents,ap lausible reaction mechanism (Scheme 4) is proposed by using 2a as am odel substrate.I nt he radical initiation stage,t he carbonate anion of Ag 2 CO 3 abstracts ap roton from 2a,t hus leading to the generation of acarboanion and AgHCO 3 ,followed by further oxidation of ac arboanion by an Ag + ion to yield the radical intermediate A.…”