Yang C.-T, Zhang Z.-Q, Liang J, Liu J.-H, Lu X.-Y, Chen H.-H, Liu L * Tsinghua University,
Beijing and University of Science and Technology of China, Hefei, P. R. of China
Copper-Catalyzed Cross-Coupling of Nonactivated Secondary Alkyl Halides and Tosylates
with Secondary Alkyl Grignard Reagents.
J. Am. Chem. Soc. 2012;
134: 11124-11127
Key words
copper - inversion - Grignard reagents
Significance
A novel method for the cross-coupling of nonactivated secondary alkyl halides and
pseudo halides with secondary Grignard reagents with a copper catalyst is described.
The addition of TMEDA and LiOMe was found to be crucial for the success of the reaction.
A broad range of functional groups including esters, amides and aryl halides, is
tolerated under the reaction conditions.
Comment
Interestingly, the reaction proceeds according to a classical SN2 mechanism with inversion of configuration. Therefore, easily accessible chiral secondary
alcohols can be converted into chiral tosylates and alkylated with a copper-catalyst
with either primary or secondary alkyl Grignard reagents to furnish the products
in high enantiomeric excess.
