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Scheme 6 Practical protocol for the selective alternate trilithiation of the
HPB frameworks.
Considering the relative thermodynamic stability of the lithiated
species, we have developed a practical protocol for the selective
alternate derivatization of the HPB framework (Scheme 6). At first,
we efficiently prepared an excess amount of MapLi from MapBr
and granular lithium in Et2O. The appropriate thermodynamic
stability of MapLi eliminates the necessity of the determination of
the exact yield of MapLi. This direct preparation of the ArLi reagent
from granular lithium can avoid the dangerous handling of the
highly pyrophoric t-BuLi at the large scale. Then, after the addition
of THF, HPB derivative 1 or 5c was directly added to the solution of
MapLi followed by quenching with TMSCl to afford the alternately
TMS-substituted compound 4 or 6c. The sufficient stability of
MapLi in the ethereal solvents realizes all of the reaction steps
over 0 1C.16 It is notable that one can synthesize various C3- or
C2v-symmetrical HPB derivatives selectively without the necessity
of the severe control of the stoichiometry of the lithiating reagent.
In conclusion, we demonstrated the utility of MesLi and MapLi
as new lithiating reagents, which realize Br/Li exchange reaction
of bromoarenes at relatively high temperature in THF. With these
reagents, we succeeded in the selective alternate trilithiation of
various HPB derivatives. These reagents should also be effective
for the Br/Li exchange reaction of a wide range of bromoarenes,
especially when they have a low solubility such as brominated PAHs.
The lithiated species from PAHs, which are difficult to be prepared
with conventional lithiating reagents, could realize diverse derivati-
zation of PAH frameworks based on the synthetic utility of organo-
lithiums.1 We believe that these reagents will be a new general
choice of lithiating reagent in Br/Li exchange reactions.
This work was supported by JSPS Grants-in-Aid for Scientific
Research on Innovative Areas ‘‘Dynamical Ordering of Bio-
molecular Systems for Creation of Integrated Functions’’
(25102005), the Yamada Science Foundation, and the Tokuyama
Science Foundation. E. Suzuki (Nihon Waters K.K.) is acknowl-
edged for HRMS measurement.
Scheme 4 Selective alternate trilithiation of HPB derivatives 5a–f.
Scheme 5 Lithiation of compound 1 with an excess amount of MesLi
or MapLi.
succeeded at the 1.5 g scale. These successes result from the
higher stability of MesLi in THF than t-BuLi. This stability realizes
the Br/Li exchange reaction of the HPB framework at relatively
high temperature, which is required for the dissolution of the low
soluble HPB derivatives.
The significant difference between MesLi and MapLi was found
when more than 3 equiv. of the ArLi reagent were added to the HPB
derivatives (Scheme 5). The use of 4.5 equiv. of MapLi for 1 afforded
almost the same crude product as that with 3.0 equiv. of MapLi
(Fig. S4, ESI†), and compound 4 was isolated in 65% yield. On the
other hand, the use of 4.5 equiv. of MesLi resulted in the ‘‘over-
lithiation’’ of the HPB framework and the complex mixture was
obtained (Fig. S4, ESI†). This difference can be interpreted by the
relative thermodynamic stability of the aryllithiums, MesLi, MapLi,
and the two kinds of lithiophenyl groups on the HPB framework
(Scheme 5). The lithiophenyl group that is not adjacent to other
lithiophenyl groups on the HPB framework should be much more
stable than MapLi and MesLi. This is the reason why 3.0 equiv. of
MesLi or MapLi can completely trilithiate the HPB frameworks. In
contrast, the lithiophenyl group that is adjacent to other lithiophenyl
groups on the HPB framework is expected to be much less stable
than MapLi, but comparably stable as MesLi. The thermodynamically
higher stability of MapLi than MesLi was confirmed by the equili-
bration experiment (Scheme S2, ESI†). Therefore, only MapLi selec-
tively afforded the alternately trilithiated species 3 regardless of the
stoichiometry of the ArLi reagent. This result demonstrates that an
ArLi reagent with an appropriate thermodynamic stability can achieve
the selective partial lithiation of polybrominated aromatics without
special care of the equivalents of the lithiating reagent.
Notes and references
1 (a) M. Schlosser, in Organometallics in Synthesis,
A Manual,
ed. M. Schlosser, Wiley, New York, 2nd edn, 2002, ch. 1; (b) J. Clayden,
Organolithiums: Selectivity for Synthesis, Pergamon, Oxford, 2002.
2 P. Stanetty and M. D. Mihovilovic, J. Org. Chem., 1997, 62, 1514.
3 For example: (a) J. Wu, M. D. Watson and K. Mu¨llen, Angew. Chem.,
Int. Ed., 2003, 42, 5329; (b) X. Feng, J. Wu, M. Ai, W. Pisula, L. Zhi,
J. P. Rabe and K. Mu¨llen, Angew. Chem., Int. Ed., 2007, 46, 3033.
4 T. Kojima and S. Hiraoka, Org. Lett., 2014, 16, 1024.
5 (a) J. Wu, W. Pisula and K. Mu¨llen, Chem. Rev., 2007, 107, 718;
(b) W. Pisula, X. Feng and K. Mu¨llen, Chem. Mater., 2011, 23, 554.
6 P. Lianhui, Z. Pengcheng, Z. Chun and X. Huibi, Huaxue Jinzhan,
2013, 25, 77 and references therein.
7 The simplest approach, the use of a larger amount of THF solvent,
was found to be unsuccessful. Another approach, the use of a larger
amount of t-BuLi in consideration of its decomposition, requires the
elaborated optimization of the equivalent of t-BuLi because the
lithiation of exactly three equivalents of the HPB frameworks is
10422 | Chem. Commun., 2014, 50, 10420--10423
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