10.1002/anie.202012496
Angewandte Chemie International Edition
COMMUNICATION
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While 12a is thermally unstable which precluded its crystallization,
on the basis of these studies we can propose a structure similar
to that of 16 (Scheme 6) but in this case the C(2) selectivity is
driven by the coordination of Li to the pyridine N, guiding the
Br/Mg-exchange to the C(2) position. If a Lewis donor is added,
this lithium-directing effect no longer operates and as shown in
Table 2 and Scheme 4, the selectivity of the Br/Mg-exchange
switches to the C(5) position.
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discussion on the thermodynamic/kinetic organometallics produced after
Scheme 6. Reaction between 1c and 10a displaying regioselective C(2)-Br
exchange facilitated by the Li---N interaction to give contacted ion pair lithium
magnesiate 12a.
a
halogen-dance, see: J. Clayden, Organolithiums: Selectivity for
Synthesis, Pergamon, Oxford, 2002.
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In conclusion, we have reported regioselective Br/Mg-exchanges
of dibromo(hetero)arenes performed by reagents of the type
R2Mg·2LiOR1 (R = sBu, nBu, R1 = 2-ethylhexyl) in toluene.
Addition of a chelating ligand such as PMDTA allowed in certain
cases a regioselectivity switch of the exchange. This switch can
be rationalized in terms of the bimetallic cooperation between Li
and Mg. The preference of Li to coordinate to the Lewis basic sites
of the substrate in toluene in the absence of any donor additives,
guides the Br/Mg-exchange to the position adjacent to these basic
sites, akin to the CIPE mechanism in metalation chemistry, thus
enabling new regioselectivities not available using turbo-Grignard
reagents.
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[17] See the Supporting Information.
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[19] Song has reported C(2)-functionalization of 10a, by replacing the Br at
the C(2) position by I, followed by an I/Mg-exchange step using iPrMgCl:
J. J. Song, N. K. Yee, Z. Tan, J. Xu, S. R. Kapadia, C. H. Senanayake,
Org. Lett. 2004, 6, 4905-4907.
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Acknowledgements
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Chem. Int. Ed. 1999, 38, 131-133; Angew. Chem. 1999, 111, 231-233;
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Science 2014, 346, 834-837.
We thank the DFG, the LMU, the Swiss National Science
Foundation (200021_188573), the ERC (StG_20101014), the
University of Bern, Albemarle (Hoechst, Germany) and BASF
(Ludwigshafen, Germany) for the generous financial support of
this research and for the generous gift of chemicals.
[22] This chemical shift compares well with those reported in the literature for
other Cpyridyl-Mg fragments, see for example: J. Francos, P. C. Gros, A.
R. Kennedy, C. T. O’Hara, Organometallics 2015, 34, 2550-2557.
Keywords: alkoxides • bromine/magnesium-exchange • lewis
bases • lithium • magnesiates
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