Synfacts 2015; 11(3): 0225
DOI: 10.1055/s-0034-1380075
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Copper-Catalyzed Hydroamination of Aryl Alkynes

Philip Kocienski
Shi S.-L, Buchwald SL * Massachusetts Institute of Technology, Cambridge, USA
Copper-Catalysed Selective Hydroamination Reactions of Alkynes.

Nature Chem. 2015;
7: 38-44
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16. Februar 2015 (online)



A new asymmetric synthesis of alkyl amines from readily available alkynes and electrophilic amine sources proceeds under mild conditions with high levels of regio- and stereocontrol. The regiochemistry of the initial hydrocupration reaction depends on the structure of the alkynes. Aryl alkynes display Markovnikov addition, whereas alkyl alkynes give anti-Markovnikov addition.



When the hydroamination reaction is performed in the absence of a proton source such as i-PrOH or EtOH, enamine intermediates (not shown) are isolated in good yield (5 examples). Catalytic cycles for the enamine formation (direct hydroamination) and the reductive hydroamination reactions are proposed. A synthesis of rivastigmine exemplifies the value of the method.