Zhu S, Buchwald SL * Massachusetts Institute of Technology, Cambridge, USA
Enantioselective CuH-Catalyzed Anti-Markovnikov Hydroamination of 1,1-Disubstituted
Alkenes.
J. Am. Chem. Soc. 2014;
136: 15913-15916
Key words
copper - hydroamination - β-chiral amines - anti-Markovnikov
Significance
β-Chiral amines are ubiquitous motifs in a range of biologically active molecules,
including pharmaceuticals and natural products. The catalytic enantioselective hydroamination
of alkenes provides an efficient route to such molecules using simple, and often commercially
available, starting materials. Herein, Buchwald and co-workers present an enantioselective
CuH-catalyzed anti-Markovnikov hydroamination of 1,1-disubstituted alkenes.
Comment
The report expands upon the authors’ previous work on the Cu-catalyzed enantioselective
hydroamination of styrene derivatives (J. Am. Chem. Soc.
2013, 135, 15746). The proposed mechanism involves hydrocupration of the 1,1-disubstitued olefin in
an anti-Markovnikov manner, which is intercepted by the hydroxylamine ester to give
the final product and a Cu(I) alkoxide complex. The active CuH catalyst is regenerated
by the addition of stoichiometric amounts of hydrosilane.
