Another Chapter into C-H Activation

C&EN had a quick blurb about Shi’s recent paper (no, not the asymmetric epoxidation guy), and I figured I’d give a little more commentary (J. Am. Chem. Soc. 2008, 130, 12901–12903).  The chemistry described in the paper falls into that category of sp³-hybridized C-H activation.  Other researchers trying to capture this chemical unicorn include Christina White’s group at UIUC (J. Am. Chem. Soc. 2008, 130, 3316; I’ve asked faculty members to invite her to do a seminar) and Guosheng Liu’s group at Shanghai Institute of Organic Chemistry (ACIE 2008, 47, 4733).

Shi’s technology involves functionalizing acetylated ketones in the 3-position.  Using a palladium(II) source (mounted on 1,2-bis(benzylsulfinyl)ethane), Shi and co-workers were able to add allylic moieties regioselectively to 1,3-dicarbonyl compounds.  The chemistry was also claimed to work intramolecularly to give exo-type five- and six-membered rings.  The hurdle in the chemistry appeared to involve overcoming the reoxidation issue (i.e. turning palladium(0) back to palladium(II)).  Shi purportedly solved this problem by running the chemistry in the presence of benzoquinone (oxidant) under an atmosphere of oxygen (reminiscent of a Wacker-type oxidation).

While the mechanistic details are a bit amorphous, the group demonstrated some really interesting regioselectivity.  Shi reacted the terminal acetate (seen below) using his optimized conditions.  Clearly, the allylbenzene is a terrific candidate for Tsuji-Trost-type chemistry, yet this product is not observed.  Rather, the acetate moiety remains in tact and the C-H activation product is isolated in 65% yield!