Copper(ii) catalysis provides cyclohexanone-derived propargylamines free of solvent or excess starting materials: sole by-product is water

Abstract

A high-yielding three-component reaction proceeds under mild, solvent-free conditions for access to a wide variety of fully-substituted propargylamines. Inexpensive copper(II) chloride catalyzes the coupling of equimolar amounts of amines, alkynes, and cyclohexanone such that the only byproduct is one equivalent of water.Scheme 1 Versatile KA 2 of cyclohexanone, amines, and alkynes. † Electronic supplementary information (ESI) available: Spectroscopic data and detailed procedures for all compounds are available online free of charge. See

Identifying a Highly Active Copper Catalyst for KA2 Reaction of Aromatic Ketones

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] However,i nc ontrast, such threecomponent couplings involving ketones, amines and alkynes (KA 2 reaction) are far from being well developed because of the extremelyl ow reactivity observed for ketones. [20][21][22][23][24][25][26][27] Recently,L arsen and co-workersu tilized CuCl 2 and Ti(OEt) 4 as the catalyst to address the problem for the reaction with alkyl ketones. [28] However,s uch reactions with aromatic ketones remain af undamentalc hallenge.…”

Copper/Titanium Catalysis Forms Fully Substituted Carbon Centers from the Direct Coupling of Acyclic Ketones, Amines, and Alkynes

“…[5] Aldehyde-amine-alkyne couplings (A 3 ) abound, [6][7][8] but as ketones are 750-times less-active than aldehydes as electrophiles, [9] the corresponding KA 2 procedure for unactivated ketones has not been reported. The three catalytic methods developed for cyclohexanones [10][11][12] rely on the fact that they undergo nucleophilic attack 300-times faster than acyclic ketones. [13] Cyclohexanone is a special case of near aldehyde-like reactivity, [14] and its corresponding ketimines [15] readily react to release torsional strain.…”

“…We recently disclosed a green [18] copper(II)-catalyzed solvent-free KA 2 of cyclohexanone that uses 1:1:1 stoichiometry of the three coupling partners, such that the sole byproduct is one equivalent of water. [12] Heating cyclohexanone (1), benzylamine (2), and 1-octyne (3) in with 5 mol % CuCl 2 produces the N-benzyl propargylamine 4 in 91 % yield (Scheme 1). However, when cyclohexanone is replaced with 2-butanone (1 a), neither ketimine intermediate nor the desired propargylamine product is observed under identical conditions (Scheme 1).…”

Polymer‐anchored copper(II) complex: an efficient reusable catalyst for the synthesis of propargylamines

“…So, further modifications have been made for the synthesis of propargylamines and their derivatives. Correspondingly, homogeneous catalysts such as Cu(I)/Cu(II), [11][12][13][14] Ag, [15][16][17] Au, [18,19] Ir, [20,21] Zn, [22][23][24] Ni, [25] Co [26] and Bi [27] have been applied for the A 3 coupling reactions. However, using homogeneous catalysts brings inherent complications in catalyst separation and reuse.…”