RT Journal Article
SR Electronic
T1 Regioselective ketone α-alkylation with simple olefins via dual activation
JF Science
JO Science
FD American Association for the Advancement of Science
SP 68
OP 72
DO 10.1126/science.1254465
VO 345
IS 6192
A1 Mo, Fanyang
A1 Dong, Guangbin
YR 2014
UL http://science.sciencemag.org/content/345/6192/68.abstract
AB Environmental and cost concerns are spurring development of chemical methods that minimize byproduct formation. In this vein, Mo and Dong present a catalyst that inserts olefins such as ethylene directly into the C-H bonds of ketones. Traditional methods to form such products rely on the preliminary reaction of the ketone with a base, followed by subsequent reaction with an alkyl halide. The authors used a ligand that simultaneously activates the ketone and guides the catalytic rhodium to the right location. This approach removes the need for the other reagents and eliminates the associated halide salt byproducts.Science, this issue p. 68 Alkylation of carbonyl compounds is a commonly used carbon-carbon bond–forming reaction. However, the conventional enolate alkylation approach remains problematic due to lack of regioselectivity, risk of overalkylation, and the need for strongly basic conditions and expensive alkyl halide reagents. Here, we describe development of a ketone-alkylation strategy using simple olefins as the alkylating agents. This strategy employs a bifunctional catalyst comprising a secondary amine and a low-valent rhodium complex capable of activating ketones and olefins simultaneously. Both cyclic and acyclic ketones can be mono-α-alkylated with simple terminal olefins, such as ethylene, propylene, 1-hexene, and styrene, selectively at the less hindered site; a large number of functional groups are tolerated. The pH/redox neutral and byproduct-free nature of this dual-activation approach shows promise for large-scale syntheses.