REPORTS
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4114 (2008).
region around the Si4 ring with a bifurcation Hückel aromatic compounds: a double intra-
threshold (0.755) similar to that reported for molecular dismutation. The formal oxidation
homoaromatic carbon rings (32). This feature states of the silicon atoms in 3a-c are +2 (SiR2),
is also present in the ELF isosurface, including +1 (SiR), and 0 (Si) as opposed to the uniform
just HOMO to HOMO−3. When the HOMO−1 oxidation state of +1 in hexasilabenzenes. We
is excluded, the ELF surface now starts to re- propose the term dismutational aromaticity for a
semble the topology of the torus link computed phenomenon that in principle should be applica-
20. D. Scheschkewitz, Angew. Chem. Int. Ed. 44, 2954 (2005).
21. D. Scheschkewitz, Angew. Chem. Int. Ed. 43, 2965 (2004).
22. Materials and methods are available as supporting
material on Science Online and contain details of
experimental procedures, analytical data, and x-ray
structure determinations. Details of the computational
procedures are available via the interactive table and the
digital repository links therein. Regarding general
information on the digital repository, see (35).
23. L. Shimoni-Livny, J. P. Glusker, C. W. Bock, Inorg. Chem.
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using the p-MOs of benzene (33).
ble to any classical Hückel aromatic compound
In order to quantify the aromaticity of 3a,b, with at least six ring atoms.
we calculated the nucleus-independent chemical
shift, NICS(0), at the center of the Si4 ring of 3b
References and Notes
24. A. Schnepf, Chem. Soc. Rev. 36, 745 (2007).
25. G. Fischer et al., Angew. Chem. Int. Ed. 44, 7884 (2005).
26. Q. Zhang et al., J. Am. Chem. Soc. 131, 9789 (2009).
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W. W. Schoeller, Angew. Chem. Int. Ed. Engl. 34, 555
(1995).
(−23.8 ppm), which indicates substantial aroma-
ticity (benzene ~ −10 ppm) but may also include
shielding effects from the s-framework (34). To
estimate these latter effects, we computed the
NICS(0) value for 4, the hypothetical saturated
hydrogenation product of 3b. This in silico
reduction has the effect of sequestering the two
Si lone pair electrons and hence suppressing the
dismutational resonance. The result (−6.4 ppm)
suggests that the strongly diatropic NICS(0)
value of 3b is truly due to aromaticity. Further
confirmation is obtained from the NICS(0) value
of −3.3 ppm for the 3Au triplet (and presumed non-
aromatic) state of 3b (resonance C) (Scheme 2).
In order to place 3b in terms of relative en-
ergy, we calculated two of its isomers with Dip
substituents: the experimentally known hexasila-
prismane (18) and the hypothetical hexasila-
benzene. Both turned out to be lower in free
energy DG298 [B3LYP/6-31G(d); 3b, 0.0; prismane,
−11.7; benzene, −4.3 kcal mol−1] with the hexasi-
labenzene surprisingly situated midway, which
raises the intriguing possibility of a future syn-
thesis of a stable hexasilabenzene.
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Aventis Foundation for financial support. Crystallographic
details were deposited with the Cambridge
(2004).
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Materials and Methods
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Interactive Table
The general formalism leading to the type of
aromaticity exemplified by 3a-c is a twofold
formal 1,2-shift of substituents in the classical
18. A. Sekiguchi, T. Yatabe, C. Kabuto, H. Sakurai,
J. Am. Chem. Soc. 115, 5853 (1993).
10 September 2009; accepted 24 November 2009
10.1126/science.1181771
ary C–H bonds with useful levels of selectivity
in complex molecule settings under prepara-
tively useful conditions (i.e., limiting amounts
of substrate) has been restricted to the realm of
enzymatic catalysis. A small-molecule catalyst
capable of performing methylene oxidations
with broad scope, predictable selectivities, and
Combined Effects on Selectivity
in Fe-Catalyzed Methylene Oxidation
Mark S. Chen and M. Christina White*
Methylene C–H bonds are among the most difficult chemical bonds to selectively functionalize because in preparatively useful yields would have a
of their abundance in organic structures and inertness to most chemical reagents. Their selective
oxidations in biosynthetic pathways underscore the power of such reactions for streamlining the
synthesis of molecules with complex oxygenation patterns. We report that an iron catalyst can achieve
methylene C–H bond oxidations in diverse natural-product settings with predictable and high
chemo-, site-, and even diastereoselectivities. Electronic, steric, and stereoelectronic factors, which
individually promote selectivity with this catalyst, are demonstrated to be powerful control elements
when operating in combination in complex molecules. This small-molecule catalyst displays site
selectivities complementary to those attained through enzymatic catalysis.
transformative effect on streamlining the prac-
tice of organic synthesis.
The paucity of methods for the oxidation of
isolated, unactivated, and nonequivalent secondary
C–H bonds underscores that they are, arguably,
the most challenging chemical bonds to selec-
tively functionalize. Reactivity for oxidizing such
bonds had been observed with several cata-
lysts, but generally in substrates where selectiv-
ethylene (secondary) C–H bonds are ical for drug metabolism and the biosynthesis of ity issues are circumvented (e.g., cyclohexane →
ubiquitous in organic structures and secondary metabolites (1, 2). Selectivity in en- cyclohexanone) (3–11) or else where reactive sites
are often viewed by organic chemists zymatic catalysis is dictated by the local chem- are either electronically activated (i.e., adjacent
M
as the inert scaffold upon which the traditional ical environment of the enzyme active site, a
chemistry of “reactive” functional groups is per- feature that inherently limits substrate scope.
formed. In contrast, the enzymatic oxidation of Despite important advances in the discovery
methylenes (i.e., C–H to C–O) is a fundamental of catalysts for C–H oxidation, the ability to di-
Department of Chemistry, Roger Adams Laboratory, University
of Illinois, Urbana, IL 61801, USA.
*To whom correspondence should be addressed. E-mail:
transformation in biological systems and is crit- rectly functionalize isolated, unactivated second- white@scs.uiuc.edu
566