Synthesis of Propargyl Amines

Fischer, C. 8c Carreira, E.M. (2004) Mgl2 an Additive in Ir(I)-Catalyzed Addition ofSUylacetylenes to Imines Expeditions Synthesis of Propargylic Amines. Synthesis, 9, 1497-1503. 

Scheme 5.4. Asymmetric synthesis of propargyl amines via the CDC reactions.

Scheme 5.8. CuBr/PINAP-catalyzed asymmetric synthesis of propargyl amines.

D hooghe, M. Van Brabandt, W. De Kimpe, N. New Synthesis of Propargylic Amines from 2-(Bromomethyl)aziridines. Intermiediacy of 3-Bromoazetidinium Salts. /. Org. Chem. 2004, 69, 2703-2710. 

Imada, Y. Yuasa, M. Nakamura, I. Muraha-shi, S.-I. Copper(I)-catalyzed amination of pro-pargyl esters. Selective synthesis of propargyl-amines, l-alken-3-ylamines, and (Z)-allyl-amines./. Org. Chem. 1994, 59, 2282-2284. 

M. K. Patil, M. Keller, B. M. Reddy, P. Pale, J. Sommer, Copper-zeolites as green catalysts for multicomponent reactions an efficient and green synthesis of propargyl amines, Eur. J. Org. Chem., 2008, 26, 4440 445. 

Three-component synthesis of propargyl amines can be performed with copper(i) complexes or in... 

Asymmetric A -CoupUng After the first enanti-oselective version of an A -coupling published by Wei and Li in 2(X)2 [125], a number of reports on the asymmetric multicomponent copper-catalyzed synthesis of propargyl-amines have subsequently appeared. The most significant examples reported from 2005 on are examined in the following text. 

Alkyne replacements have also been reported. In 2008, Sakai et al. described the use of alkynylsilanes instead of terminal alkynes in the Cu-catalyzed synthesis of propargyl-amines, which was applicable to both secondary and primary aliphatic amines, although the latter afforded the corresponding products in low yield [145]. Very recently. Van der Eycken et al. applied the A -coupling to the C—H alkylation of azoles through a copper-catalyzed hetero-arene-amine-aldehyde/ketone coupling [146]. This reaction is proposed to proceed through the initial condensation of... 

N. Sakai, N. Uchida, T. Konakahara, Synlett 2008, 1515-1519. Facile and selective synthesis of propargylic amines and 1,6-diynes one-pot three-component coupling reactions of alkynylsilanes, aldehydes and amines by a cooperative catalytic system comprised of CuCl and Cu(OTf)j. 

A gold-promoted intermolecular coupling of ketones, secondaiy amines and allgmes under neat eonditions was reported by Ji and coworkers in 2011. This methodology allowed for the synthesis of propargylic amines bearing a quaternary earbon. The reaction proceeded under mild conditions, 60 °C, 4 mol% of gold(iii) bromide was used as catalyst, and relatively short reaction times were employed (Scheme 16.23). 

Scheme 16.24 Gold-promoted synthesis of propargylic amines by three-component coupling under neat conditions.

The author expected that a reaction with a chiral ligand which coordinates to a copper atom could produce optically active 2-(aminomethyl)indoles. Knochel recently developed a novel asymmetric synthesis of chiral propargylamines with excellent ee values through a copper-catalyzed asymmetric Mannich-type reaction of alkynes with an aldehyde and a secondary amine using QUINAP as a chiral ligand (up to 98% ee) [1-3]. Carreira reported the similar synthesis of propargylic amine in up to 99% ee with PINAP [4, 5]. The author initially examined the... 

Zani, L., Eichhorn, T., Bolm, C. (2007). Dimethylzinc-mediated, enantioselective synthesis of propargylic amines. Chemistry - A Enropean Journal, 13, 2587-2600. 

The cascade three-component coupling of aldehydes, terminal alkynes, and amines is one of the most convenient methods for the synthesis of propargylic amines with water as the only theoretical by-product. A recent example is the three-component couphng of aldehydes, alkynes, and carbamates with copper(II) triflate as catalyst, which furnished a diverse range of propargylcarbamates 103 in moderate to high yields, and no other cocatalyst or ligand is required in this transformation (Scheme 5.68) [71],... 

---