Organic & Biomolecular Chemistry
Paper
ITN 215193). The National Research School Combination
Catalysis (NRSCC) is acknowledged for further financial
Conclusions
A rapidly growing number of publications discussing the appli- support. The X-ray diffractometer has been financed by the
cation of the promising small molecular catalyst Fe(BPBP) in Netherlands Organization for Scientific Research (NWO).
various C–H and CvC bond oxidation processes is an evident
sign of its appreciation by the scientific community. Despite
the efforts at making this catalyst more efficient in several
challenging C–H oxidations, its recently developed and more
Notes and references
advanced alternatives are comparable or less accessible from a
synthetic point of view and their showcase of preparative oxi-
dations usually affords submillimolar product quantities. In
contrast, the mix-1 catalyst (rac-/R,S-1 ca. 75/25) presented here
can be prepared on a multi-gram scale in two steps from a
crude 2,2′-bipyrrolidine mixture. The R,S-isomer component
plays only a spectator role in both C–H and CvC bond oxi-
dation reactions. The presence of this inactive catalyst isomer
does not affect the overall reactivity and selectivity of the mix-1
catalyst system. Most strikingly, the mix-1 catalyst retained
the most crucial selectivity properties of its optically pure
components, e.g. a high ketone over alcohol ratio in methylene
oxidations and high selectivity towards tertiary alcohols
along with complete retention of the initial tertiary carbon
center configuration in C–H oxidations. The mix-1 catalyst
is also applicable to the functionalization of more complex
substrates, e.g. the transformation of (−)-ambroxide into
(+)-sclareolide proceeds in a very similar manner with mix-1 as
with itself enantiopure S,S-, and R,R-congenders. The mix-1
catalyst is even useful in a challenging synthesis of oxo-sclareo-
lides, in which the product distribution depends on the chiral
catalyst shape. Importantly, the C–H oxidations mediated
by this simple iron complex in combination with hydrogen
peroxide have been proven to be scalable without compromis-
ing on the reaction selectivity.
1 (a) K. Chen and P. S. Baran, Nature, 2009, 459, 824;
(b) A. Mendoza, Y. Ishihara and P. S. Baran, Nat. Chem.,
2012, 4, 21.
2 A. Company, L. Gómez and M. Costas, in Iron-Containing
Enzymes, Versatile Catalysts of Hydroxylation Reactions
in Nature, ed. S. P. De Visser and D. Kumar, RSC,
Cambridge, 2011.
3 C–H bond oxidation: (a) M. S. Chen and M. C. White,
Science, 2007, 318, 783; (b) L. Gómez, I. Garcia-Bosh,
A. Company, J. Benet-Buchholz, A. Polo, X. Sala, X. Ribas
and M. Costas, Angew. Chem., Int. Ed., 2009, 48, 5720;
(c) Y. Hitomi, K. Arakawa, T. Funabiki and M. Kodera,
Angew. Chem., Int. Ed., 2012, 51, 3448; (d) R. V. Ottenbacher,
D. G. Samsonenko, E. P. Talsi and K. P. Bryliakov,
Org. Lett.,
2012, 14, 4310;
syn-dihydroxylation:
(e) E. N. Jacobsen, I. Marko, W. S. Mungall, G. Schroeder
and K. B. Sharpless, J. Am. Chem. Soc., 1988, 110, 1968;
(f) K. Suzuki, P. D. Oldenburg and L. Que Jr., Angew. Chem.,
Int.
Ed.,
2008,
47,
1887;
CvC
epoxidation:
(g) E. N. Jacobsen, W. Zhang, A. R. Muci, J. R. Ecker and
L. Deng, J. Am. Chem. Soc., 1991, 113, 7063;
(h) F. G. Gelalcha, B. Bitterlich, G. Anilkumar, M. K. Tse
and M. Beller, Angew. Chem., Int. Ed., 2007, 46, 7293;
(i) B. Wang, C. Miao, S. Wang, C. Xia and W. Sun, Chem.–
Eur. J., 2012, 18, 6750.
Moreover, the mix-1/H2O2 system is very promising in pre-
parative epoxidation reactions, where the amount of acetic
acid – a commonly used additive (or even a co-solvent) – can
be remarkably reduced to less than 2 mol% or even totally
eliminated. Under these conditions, a high catalyst activity
(TON approaching 1000) is obtained in the oxidation of elec-
tron-rich olefins, where the epoxides are the only isolated
products. A highly selective monoepoxidation of dienes is only
possible if the substrate molecule bears electronically different
CvC fragments. This mix-1/H2O2 epoxidation system tolerates
functional groups like primary alcohols and dicarboxylic acids.
Overall, we have shown the practical use of an easy
to prepare iron complex in a range of challenging organic
reactions, which now become much more affordable.
We believe that our practical observations on the Fe(BPBP)
complex reactivity will further contribute to the popularization
of this promising catalyst and will further broaden its appli-
cation in organic synthesis.
4 (a) M. S. Chen and M. C. White, Science, 2010, 327, 566;
(b) M. A. Bigi, S. A. Reed and M. C. White, Nat. Chem.,
2011, 3, 216.
5 M. A. Bigi, S. A. Reed and M. C. White, J. Am. Chem. Soc.,
2012, 134, 9721.
6 (a) P. E. Gormisky and M. C. White, J. Am. Chem. Soc., 2013,
135, 14052; (b) L. Gómez, M. Canta, D. Font, I. Prat,
X. Ribas and M. Costas, J. Org. Chem., 2013, 78, 1421.
7 Large scale synthesis and resolution protocol: (a) T. Oishi,
M. Hirama, L. R. Sita and S. Masamune, Synthesis, 1991,
789; (b) S. E. Denmark, J. Fu and M. J. Lawler, Org. Synth.,
2006, 83, 121; enantioselective synthesis of 2,2′-bipyrrol-
idines:
(c) A. Alexakis, A. Tomassini, C. Chouillet,
S. Roland, P. Mangeney and G. Bernardinelli, Angew.
Chem., Int. Ed., 2000, 39, 4093; (d) X.-N. Song and Z.-J. Yao,
Tetrahedron, 2010, 66, 2589.
8 Recent advances on diastereoselective synthesis of BPBP
and its derivatives: C. H. Müller, R. Fröhlich, C. G. Daniliuc
and U. Hennecke, Org. Lett., 2012, 14, 5944.
9 (a) O. Y. Lyakin, R. V. Ottenbacher, K. P. Bryliakov and
E. P. Talsi, ACS Catal., 2012, 2, 1196; (b) O. Cussó, I. Garcia-
Bosch, X. Ribas, J. Lloret-Fillol and M. Costas, J. Am. Chem.
Soc., 2013, 135, 14871.
Acknowledgements
This work was supported by 7PCRD EU funds from the Marie-
Curie Initial Training Network NANO-HOST (grant agreement
This journal is © The Royal Society of Chemistry 2014
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