Very Mild, Enantioselective Synthesis of Propargylamines Catalyzed by Copper(I)−Bisimine Complexes

Abstract

The stereoselective addition of aryl- and alkylacetylene derivatives to imines was studied. The reaction is catalyzed by copper complexes of enantiomerically pure bisimines, readily prepared in very high yields from the commercially available binaphthyl diamine. A very simple experimental procedure allowed to obtain at room temperature optically active propargylamines in high yields and enantioselectivity. Interestingly, bisimine/copper(I) complexes were able to promote the direct, enantioselective, catalytic addition to imines of alkylacetylenes. The effects of catalyst loading and other reaction parameters on the stereochemical outcome of the transformation were investigated. The extremely convenient methodology, the mild reaction conditions, and the possibility of a modular approach for developing new and more efficient bisimine-based chiral ligands make the present methodology very attractive.

The synthesis of chiral N-tosylatedaminoimine ligands and their application in enantioselective addition of phenylacetylene to imines

“…The procedure was very simple: to a mixture of imine, copper(I) triflate benzene complex and chiral ligand was added an alkynylzinc reagent and the reaction was carried out at room temperature for 24 h and worked up to obtain the required product. 9 Only trace amounts of the product were detected when the reaction was carried out in the absence of copper(I) triflate benzene complex (entry 18). The result indicated that copper(I) was very important for catalyzing this reaction.…”

“…9 Very recently, Bolm et al developed a one-pot, enantioselective synthesis of N-aryl propargylic amines using alkynylation reagents in combination with aldehydes and o-methoxyaniline as starting materials. 10 In contrast to the enantioselective alkynylation of aldehydes in which considerable progress has been made in recent years, the enantioselective alkynylzinc addition to imines still remains less developed.…”

A hexadentate Schiff base ligand which undergoes reversible, diastereoselective addition of methanol

“…Given the facile nature of the amine-aldehyde condensation in the synthesis of Schiff base ligands, and the wealth of oligopyridine-based coordination chemistry and their applications in asymmetric catalysis [3], it is rather surprising that the two regimes have been combined to only a limited extent. Ligand 1 (Scheme 1) has been known for over a decade [4][5][6][7][8][9][10]. Rigorously anhydrous conditions are required for its preparation (dry toluene or CH 2 Cl 2 in the presence of molecular sieves) from 2,2 0 -diamino-1,1 0 -binaphthyl and pyridine-2-carbaldehyde.…”

“…Rigorously anhydrous conditions are required for its preparation (dry toluene or CH 2 Cl 2 in the presence of molecular sieves) from 2,2 0 -diamino-1,1 0 -binaphthyl and pyridine-2-carbaldehyde. Although the ligand has been isolated [4][5][6][7][8][9][10] and structurally characterized [10], it is significant that Hannon et al reported difficulties in isolating 1 and chose instead to assemble silver(I) and copper(I) complexes of the tetradentate ligand in one-pot syntheses from 2,2 0 -diamino-1,1 0 -binaphthyl, pyridine-2-carbaldehyde and appropriate metal salts [6]. Recently, we reported the use of hexadentate ligands (R)-2 and (S)-2 in controlling the diastereoselective assembly of mononuclear iron(II) helicates [11].…”

Electrostatic immobilisation of copper(I) and copper(II) bis(oxazolinyl)pyridine catalysts on silica: application to the synthesis of propargylamines via direct addition of terminal alkynes to imines

“…1,3,4 Propargylamines are useful building blocks in organic chemistry and have found use in synthesis due to the fact that elements of their structure are found in natural products 5 and compounds of pharmaceutical interest. 6 They have been used in the synthesis of pyrrolidines, 7 oxazoles 8 and dynemicins.…”