Ligand Topology Tuning of Iron-Catalyzed Hydrocarbon Oxidations We thank the National Institutes of Health for financial support (GM33162 to L.Q.) and Fundacio La Caixa for a postdoctoral fellowship (M.C.).

Abstract

Nature has evolved a number of nonheme iron oxygenases capable of the stereoselective oxidation of CÀH and CC bonds. [1,2] Still far from being understood are the factors that control the ability of iron centers to catalyze a range of reactions such as alkane hydroxylation, olefin epoxidation, and olefin cis-dihydroxylation. In our effort to develop bioinspired nonheme iron catalysts, we have discovered a family of iron complexes with tetradentate pyridine/amine ligands that, in combination with H 2 O 2 , are capable of carrying out the above transformations with high stereoselectivity. [3±7] Enantioselectivity has also been obtained with the chiral ligand N,N'-bis(2-pyridylmethyl)-N,N'-dimethyl-trans-1,2-di-aminocyclohexane (bpmcn). [8] A priori, tetradentate ligands with this type of architecture can adopt three different topologies (Scheme 1). [9±11] While Schiff×s base ligands (e.g. salen) often afford complexes with the trans or planar Scheme 1. Three different topologies that can be adopted by tetradentate ligands such as N,topology, ligands such as bpmcn in which the imine functionalities have been reduced give rise to complexes with cis-a and/or cis-b topologies. We have undertaken a series of systematic studies to uncover the factors that control the catalytic reactivity of the nonheme iron center in this family of complexes. [5±7] Herein we report the unexpectedly distinct oxidation behavior of two [Fe II (bpmcn)] catalysts, whose structures differ only by their ligand topologies.[Fe II (bpmcn)(OTf) 2 ] (1, OTf trifluoromethanesulfonate) complexes in both cis-a and cis-b ligand topologies can be synthesized by independent routes, and the structures of a-1 and the related b-[Fe II (5-Me 2 -bpmcn)(OTf) 2 ] have recently been established by crystallography. [8, 12] The NMR spectra of the two complexes strongly suggest that they each retain their respective ligand topologies in solution (Figure 1). Complex Figure 1. 1 H NMR spectra of a-[Fe II (bpmcn)(CD 3 CN) 2 ] 2 (a) and b-[Fe II (bpmcn)(CD 3 CN) 2 ] 2 (b) in CD 3 CN solution at ambient temperature.a-1 exhibits 12 paramagnetically shifted signals, as expected for a C 2 -symmetric high-spin Fe II complex, while the b isomer shows 24 resonances. These isomers do not interconvert even after heating solutions of either isomer in acetonitrile at 50 8C for one day. The high barrier to interconversion arises from the fact that the N-methyl groups of the ligand have distinct [6] Immunogold-Silver Staining: Principles, Methods and Applications (Ed.: M. A. ] E 1 V versus NHE(Au) and E 1/2 À 0.4 V versus NHE(NH 2 OH); NHE normal hydrogen electrode. A. J. Bard, Encyclopedia of

Iron‐Catalyzed Asymmetric Olefin cis‐Dihydroxylation with 97 % Enantiomeric Excess

“…This catalyst is quite cis ‐diol‐selective, affording a diol/epoxide ratio of about 6 for cyclooctene oxidation and as much as 60 or greater for the oxidation of 1‐octene, styrene, and crotonate. As can be seen in the trend for the 1 – 3 series and illustrated previously for the BPMCN complexes,10b,c the high selectivity for cis ‐diol undoubtedly arises from the introduction of the α‐methyl substituents on the two pyridine ligands. As the steric bulk at that position increases, the catalyst goes from being epoxide‐selective, as in the case of 1 , to being cis ‐diol‐selective in 2 , and even more cis ‐diol‐selective in 3 .…”

“…Interestingly, all ligands in the BPBP series adopt a cis ‐α topology upon complex formation. In contrast, the BPMCN ligand forms both cis ‐α and cis ‐β iron(II) complexes,10b whereas 6‐Me 2 ‐BPMCN adopts a cis ‐β ligand topology in 5 10c. It is clear from an examination of the structures in Figure 2 that the cis ‐α topology in 1 – 3 is determined by the constraints of the bipyrrolidine moiety.…”

The Mechanism of Stereospecific CH Oxidation by Fe(Pytacn) Complexes: Bioinspired Non‐Heme Iron Catalysts Containing cis‐Labile Exchangeable Sites

“…The distinct oxidative reactivity of isomers O A and O B may be tentatively rationalized by taking into consideration that the two tautomers differ, among other structural aspects, in the nature of the ligand in a relative trans position with respect to the terminal oxo site, and in the relative orientation of the pyridine ring with respect to the Fe‐oxo vector. Indeed, both aspects have been recognized to have a defining role in the oxidative properties of high valent oxo‐iron species,17b, 31 and should be considered. However, since the relative reactivities of O A and O B isomers appear to be more distinct in 2 than in 1 , and the relative trans effect is the same for both pairs, the relative orientation of the pyridine appears to be the most likely defining factor.…”

The Iron(II) Complex [Fe(CF3SO3)2(mcp)] as a Convenient, Readily Available Catalyst for the Selective Oxidation of Methylenic Sites in Alkanes

“…The preparation of [Fe(II)(CF 3 SO 3 ) 2 (mcp)], Fe‐mcp on the mg scale was previously described,14 but in order to illustrate the ready accessibility of this catalyst, a multigram scale preparation was performed. Starting from 26.8 g of (+/−)‐ trans ‐diaminocyclohexane, the racemic diamine was resolved using (−)‐ D ‐tartaric acid, obtaining the desired ( S,S )‐diaminocyclohexane in 99% yield with ≥99 % enantiomeric purity as confirmed by chiral GC, without the need of recrystallization.…”