esters, carbamates, amides, or Si-O bonds. The presence
of such reactive groups hampers or even precludes further
derivatization using organolithium or Grignard reagents. We
here present a preparative route to functionalized CS-
dendrimers in which ligand moieties are bound to the
carbosilane core via σ Si-C bonds, which are inert under
most catalytic conditions.
Previously we have shown that 4-[(dimethylamino)methyl]-
phenyl- and 3,5-[bis(dimethylamino)methyl]phenyl-func-
tionalized CS-dendrimers are easily accessible by reaction
of Me2SiCl-terminated carbosilane dendrimers with the
corresponding organolithium or Grignard reagents.8 To
further explore the scope of this method we have reacted
Me2SiCl-terminated carbosilanes 1a and 1b,9 (Scheme 1; the
In particular, the 4-bromophenyl-functionalized CS-den-
drimers 2d and 2e are valuable starting materials that allow
the easy introduction of a variety of functional groups. This
may be realized by substitution of the bromine atoms in 2d
and 2e by lithium.
It is well known that the aryl groups in o-aminoarene-
functionalized CS-dendrimers can be quantitatively lithiated
via heteroatom-assisted lithiation reactions. The lithiation
products may then be easily converted by transmetalation
into a wide variety of other organometallic derivatives.8
Accordingly, a synthetic protocol was developed to substitute
all bromine atoms in 2d and 2e by lithium atoms. These
4-lithiophenyl-functionalized CS-dendrimers appear to be
excellent starting materials for the synthesis of a variety of
periphery-functionalized dendrimers using suitable electro-
philes.
Reaction of 2d or 2e with 4 or 12 equiv, respectively, of
n-BuLi, gave sticky insoluble materials, which were not
further analyzed but directly converted into products (see
Scheme 2).
Scheme 1
The lithiation reaction, i.e., the exchange of bromine for
lithium, is quantitative, as was shown by hydrolysis of freshly
prepared 5a. The phenyl-functionalized derivative 2f (see
Scheme 1) was the only product obtained. Analysis of the
product by MALDI-TOF showed the complete absence of
bromine-containing products.
Reaction of in situ prepared 5a or 5b with Ph2PCl afforded
the corresponding diphenylphosphino derivatives 6a and 6b
in high yield. Because these materials are rather susceptible
to oxidation, for analytical purposes (elemental analysis and
MALDI-TOF MS) 6a and 6b were converted to the corre-
sponding phosphinoxide compounds 6a′ and 6b′ via a H2O2
oxidation reaction. (Note that the CS-dendrimer backbone
remained unaffected.) The dicyclohexylphosphino compound
6c was prepared similarly from c-Hex2PCl.
The feasibility of this approach for the introduction of
acyl-, hydroxy-, or amino-functionalized groups at the
periphery of CS-dendrimers was tested by reacting 5a with
DMF, acetone, or N-tert-butyl(phenyl)imine to give the
corresponding derivatives 7, 9, and 8 (see Scheme 2).
Whereas 7 and 9 were isolated analytically pure after workup,
8 contained about 20% material resulting from partial
protolysis of aryl-Li groups present in 5a. A separate
experiment demonstrated that reaction of 4-(trimethylsilyl)-
phenyllithium with N-tert-butyl(phenyl)imine, under various
reaction conditions, also produced considerable amounts
(20-25%) of the protolysis product trimethylsilylbenzene.
Previously it has been shown that the heteroatom-assisted
ortho-lithiation of N-alkyl(phenyl)imines is a competing
reaction during the addition of organolithium compounds to
the imine bond, especially when bulky N-substituents are
present.12 We believe that in our case a comparable Li-H
exchange occurs between the Li atoms in 5a and one of the
ortho-H atoms in N-tert-butyl(phenyl)imine.
encircled “snowflake” symbol is introduced by the authors
to represent a dendritic support), with various (protected)
functionalized arylmagnesium or aryllithium reagents.
When 1a or 1b is reacted with a slight excess of the
Grignard reagent derived from Me2t-BuSi-protected 4-bro-
mophenol or 4-bromo-N-methylaniline, the silyl-protected
functionalized dendrimers 2a, 2b, and 2c are formed
quantitatively.10 After workup, the products were obtained
1
in pure form and were characterized by H and 13C NMR
spectroscopy, as well as MALDI-TOF MS and elemental
analysis (see Supporting Information).
The 4-hydroxyphenyl- and 4-N-methylaminophenyl-func-
tionalized CS-dendrimers 3 and 4 were obtained by depro-
tection with Et3NHF in THF. These CS-dendrimers can be
easily converted into further functionalized molecules using
straightforward organic reactions such as esterification or
amide formation.11
(8) Kleij, A. W.; Kleijn, H.; Jastrzebski, J. T. B. H.; Smeets, W. J. J.;
Spek, A. L.; van Koten, G. Organometallics 1999, 18, 268.
(9) Van der Made, A. W.; van Leeuwen, P. W. N. M. J. Chem. Soc.,
Chem. Commun. 1992, 1400.
(10) As a result of the excess Grignard reagent Me2t-BuSi-protected
phenol or N-methyl aniline was also formed.
(11) Recently we reported the synthesis of 4-(hydroxymethyl)phenyl-
substitued CS-dendrimers and their subsequent conversion into phosphino
carboxylic esters; see ref 5.
(12) Cliffe, I. A.; Crossley, R.; Shepher, R. G. Synthesis 1985, 1138.
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Org. Lett., Vol. 2, No. 11, 2000