The catalytic enantioselective formation of new C À C bonds is an important class of reactions.[1] Especially attractive are multicomponent reactions which allow the formation of several bonds including new CÀC bonds in a one-pot procedure.[2] For achieving optimum atom economy [3] and avoiding the production of stoichiometric amounts of metal salts as by-products, we [4] and others [5] have examined the use of an alkyne as the precursor for the nucleophilic reaction component. Alkynes of type 1 can be deprotonated catalytically in situ by means of cesium salts and reacted subsequently with aldehydes and ketones, leading to propargyl alcohols. [6] Recently, we have shown that various enamines react with terminal alkynes in the presence of copper(i) salts and quinap (2), [7] providing propargylamines in up to 90 % ee.[4]In order to avoid the generation of sensitive enamines and to extend the scope of this propargylamine synthesis to nonenolizable aldehydes (i.e. aldehydes from which enamines cannot be prepared), we have examined a new threecomponent reaction [8] between an alkyne 1, an aldehyde 3, and a secondary amine 4. We have found that propargylamines of type 5 are formed in toluene at room temperature in the presence of CuBr (5 mol %), (R)-quinap ((R)-2) (5.5 mol %), and molecular sieves 4 in excellent yields (up to 99 %) and good enantioselectivities (up to 96 % ee; Scheme 1 and Table 1).The reaction is usually complete within 12 to 48 h for the racemic reaction without ligand and within one to six days for the enantioselective reaction with high yields in most cases. The alkyne can bear either an aryl substituent (R 1 = Ph) or an alkyl substituent (R 1 = Bu; entries 1 and 2 in Table 1). The resulting propargylamines 5 a and 5 b were obtained in 98 and 85 % yield and 86 and 82 % ee, respectively. Branched aliphatic aldehydes like isobutyraldehyde lead to the expected propargylamines 5 c and 5 d in 60 and 99 % yield and 84 and 83 % ee, respectively (entries 3 and 4). The use of

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Propargylamines are important as both synthetic intermediates for the preparation of polyfunctional amino derivatives and as biologically active compounds. [1] Their preparation in enantiomerically enriched form is therefore of great importance. Although several diastereo-and enantioselective syntheses have been developed, [2] until now no metal-catalyzed enantioselective synthesis of propargylamines is known. [3] We report herein a new copper(i)-catalyzed enantioselective addition of alkynes [4] to enamines. First, we examined the racemic synthesis of propargylamines by metal-complex catalysis. Various metal salts, including Sc(OTf) 3 , Zn(OTf) 2 , Yb(OTf) 3 , and Cu I and Cu II salts, [5] were tested as catalysts. Copper(i) and copper(ii) bromide proved to give the fastest conversions. We chose test enamines [6] with readily removable protecting groups such as an allyl or a benzyl group. Enamines 1 a ± h (1.2 ± 1.5 equiv) reacted readily with terminal alkynes 2 a ± k in toluene in the presence of copper(i) bromide (5 mol %) to give propargylic amines of type 3 (Scheme 1, Table 1) under mild reaction conditions. R 1 N R 2 R 4 R 3 R 5 R 1 N R 4 R 3 R 2 R 5 CuBr (5 mol%) toluene RT or 60 °C 3 -24 h + 1a-h 2a-k 3a-r 66 -98 % Scheme 1. Synthesis of propargylamines by the addition of alkynes to enamines.

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