A Predictably Selective Aliphatic C–H Oxidation Reaction for Complex Molecule Synthesis
Mark S. Chen and
M. Christina White*
Realizing the extraordinary potential of unactivated sp
3 C–H
bond oxidation in organic synthesis requires the discovery of
catalysts that are both highly reactive and predictably selective.
We report an iron (Fe)–based small molecule catalyst that
uses hydrogen peroxide (H
2O
2) to oxidize a broad range of substrates.
Predictable selectivity is achieved solely on the basis of the
electronic and steric properties of the C–H bonds, without
the need for directing groups. Additionally, carboxylate directing
groups may be used to furnish five-membered ring lactone products.
We demonstrate that these three modes of selectivity enable
the predictable oxidation of complex natural products and their
derivatives at specific C–H bonds with preparatively useful
yields. This type of general and predictable reactivity stands
to enable aliphatic C–H oxidation as a method for streamlining
complex molecule synthesis.
* To whom correspondence should be addressed. E-mail: white{at}scs.uiuc.edu
