Iron Lady

Figure 1. The Iron Catalyst used in Ref. [4]. (Taken from Ref. [4])

I have a strong interest in Prof. M. Christina White’s work (University of Illinois) for quite some time. My very first fascination in her research originated from an impressive Science paper back in 2007[1]. What they have achieved in that investigation was that they enabled C-H oxidations of organic substrates using an iron catalyst. These represent examples of C-H activations, and are full of cytochrome P450 undertones. An ‘alter ego’ of her chemistry resides in the use of a Pd(II) system – with the theme of C-H activation intact. This catalyst leads to various useful reactions from allylic aminations {2} to oxidative Heck reaction [3].

On NATURE CHEMISTRY this week, the group has developed a nice iron hydroxylation catalyst to carry out useful organic transformations (Figure 2). The idea is biomimetic, which means that is inspired by Nature. [4]


Figure 2. Diversification with an Iron catalyst. (Taken from [4]).

The idea is as follows. One single ‘non-haem’ iron enzyme is capable of doing a number of diverse reactions. The rationale behind this versatility is that the enzyme can direct the ‘radical intermediates’ from the reactions towards different reaction pathways (i.e. different reaction outcomes) with active site control and substrate modifications. [4] Thus the group has ‘diverted ‘ their designed iron catalyst to 2 specific types of reactions – hydroxylase / desaturation reactions with aliphatic C-H bonds as substrates. This also operates via substrate control -the presence of a carboxylic acid functionality is required. Not only have they probed and gained insight about the inner mechanisms, they have also employed the iron catalyst to diversification of natural products.

On Thursday (27th Jan 2011) there was also an advance article of the group from Angew Chemie. Int. Ed. (Figure 3) [5] They have discovered that even without preorganizations, they use a macrocyclization reaction, either a Yamaguchi esterification or their Pd (II)-catalyzed C-H Oxidation strategy, towards the natural product erythromycin, a popular target in the synthetic community.


Figure 3. Macrocyclizations without biasing elements. (Taken from [5]).

References:

1. A Predictably Selective Aliphatic C–H Oxidation Reaction for Complex Molecule Synthesis
Mark S. Chen and M. Christina White
Science 318, 783 (2007)
DOI: 10.1126/science.1148597

2. For some recent examples, see:
(a) Diversification of a β-lactam pharmacophore via allylic C-H amination: accelerating effect of Lewis acid co-catalyst.
X. Qi, G. T. Rice, M. S. Lall, M. S. Plummer, M. C. White
Tetrahedron, 2010, 66, 4816

(b) Allylic C-H Amination for Preparation of syn-1,3-Amino Alcohol Motifs."
G.T. Rice and M.C. White
J. Am. Chem. Soc. 2009, 131, 11707
DOI: 10.1021/ja9054959

3. "A General and Highly Selective Chelate-Controlled Intermolecular Oxidative Heck Reaction."
J.H. Delcamp; A.P. Brucks; and M.C. White
J. Am. Chem. Soc. 2008
DOI: 10.1021/ja804120r

4. Diverting non-haem iron catalysed aliphatic C–H hydroxylations towards desaturations
Marinus A. Bigi, Sean A. Reed & M. Christina White
Nature Chemistry
doi:10.1038/nchem.967
Published online: 23 January 2011

5. On the Macrocyclization of the Erythromycin Core: Preorganization is Not Required
Erik M. Stang and M. Christina White
Angew. Chemie. Int. Ed.
DOI: 10.1002/anie.201007309
Article first published online: 27 Jan 2011