Copper‐Catalyzed Diversity‐Oriented Three‐ and Five‐ Component Synthesis of Mono‐ and Dipropargylic Amines via Coupling of Alkynes, α‐Amino Esters and Aldehydes

Abstract

Mono‐ as well as dipropargylic amines were synthesized using α‐amino esters as inexpensive building blocks under a single catalytic system (copper bromide, 100 °C, 4 h, toluene) where the reactant ratio (1a/2a/3a) acted as product specific switch. Both secondary (mono) as well as tertiary (di) propargylic amines formed via three‐ and five‐component coupling exhibited wide substrate scope with moderate to good yields and satisfactory diastereoselectivity in a few cases. The practical utility of the method is enhanced by providing a facile access to enantiopure propargylic amines via lipase‐catalyzed resolution along with synthesis of unsymmetrical dipropargylic amines, secondary propargylic amines bearing quaternary carbon centers and imidazolidin‐2‐ones.magnified image

Recent Advances in the A3 Coupling Reactions and their Applications

“…In continuation of their work with A 3 coupling reactions, Van der Eycken et al synthesized mono‐ and dipropargylic amines ( 123/124 ) using α‐amino esters 122 as economical building blocks under a single catalytic system (copper bromide, 100 °C, 4 h, toluene; Scheme ) . Use of one equiv.…”

Manganese‐Catalyzed Multicomponent Synthesis of Tetrasubstituted Propargylamines: System Development and Theoretical Study

“…[1] These characteristics make propargylamines susceptible to a variety of chemical transformations, thus fulfilling the conditions which have been established by the diversity-oriented synthesis strategy and natural product synthesis. [1,2,[10][11][12][13][14][15][16][17] Moreover, through the integration of carbon dioxide or other small molecules, propargylamines can serve as intermediates or precursors for the synthesis of various heterocyclic compounds, [1] such as oxazolidinones, [18,19] same as their propargylic alcohol congeners. [20] Amongst others, propargylamines can be accessed in a facile manner through catalytic, multicomponent reaction protocols, [1,2,[21][22][23][24][25] thus minimizing the required effort, time, and the generation of waste related to multistep processes.…”

Double A3‐Coupling of Primary Amines Catalysed by Gold Complexes

“…The method reported here involves the five-component coupling of ap rimary amine, ethynyltrimethylsilane (TMS-acetylene) and formaldehyde in a1:2.5:3.5 ratio catalysed by cationic [LAu(NCMe)][SbF 6 ]( 1)[ Ta ble 1].I nitial studies began using aniline (2), TMS-acetylene (3)and aqueous(37 %) formaldehyde (4)a sr eagents [ Table 1, Scheme (Top)].F ormation of N-phenylmethanimine (5), N- (3-(trimethylsilyl)prop-2-yn-1-yl)aniline (6), N-methylene-N- (3-(trimethylsilyl)prop-2-yn-1-yl)benzenaminium (7)a nd N,N-bis (3-(trimethylsilyl)prop-2-yn-1-yl)aniline (8) [ Table 1, Scheme] either as intermediates or as final reaction product, respectively,w as observed. Compound 8 is formed in high yield and high selectivity.O ne important conclusion from the results presented in entries 2-4 is that the cationic Au I complex (1)i sm ore activei nC H 2 Cl 2 as solvent than in ethanol or toluene.…”

“…[3] In one of the precedent works, [4] this reaction was catalysedb ya mixture of RuCl 3 /CuBr at al oading ranging between 21 to 25 mol %. [5] In view of the current state of art, it would be desirable to expand this five-component coupling to primary amines for the preparation of new dipropargyl amines by using more efficient and recoverable catalyst in lowerm olar ratios. In another recents tudy on this catalytic multicomponent coupling, stoichiometric amounts of Na 2 CO 3 as additive togetherw ith 20 % CuBr as catalyst was required.…”