six L-tartrate-derived units in the outer layer and three
D-chiral units in the inner layer (Figure 1) were compared
At the outset of this study, it was predicted that the
asymmetric functionalization of tris ether 8 (Scheme 2) with
Scheme 1. Synthesis of the Electrophile (S,S)-7
bromide (S,S)-7 would lead to the homochiral polyether
(Sinner,Souter)-9 using chiral base (S,R,R,S)-5 and its hetero-
chiral partner (Rinner,Souter)-9 using chiral base (R,S,S,R)-5
(Scheme 2). The required bromide, (S,S)-7, was prepared
by the route depicted in Scheme 1. Commercially available
diethyl 5-(hydroxymethyl)isophthalate 3 was protected as its
triisopropylsilyl ether, reduced with lithium aluminum hy-
dride, converted into a dimethyl ether, and complexed with
hexacarbonylchromium(0) to give the novel complex 4.
Deprotonation of 4 with 1.5 equiv of the chiral base
(S,R,R,S)-5 followed by an iodomethane quench installed the
two stereogenic centers destined for the periphery of target
molecules 9 in 100% de and 90% ee. Finally, oxidative
removal of the tricarbonylchromium(0) unit from (S,S)-6
followed by deprotection and bromination of the benzylic
alcohol gave the desired electrophile (S,S)-7. [Repetition of
the sequence using chiral base (R,S,S,R)-5 gave the enan-
tiomeric bromide (R,R)-7 in 48% overall yield from diester
3.]
With bromide 7 in hand, the readily available tricarbon-
ylchromium(0) complex 88 was deprotonated with 3 equiv
of chiral base (S,R,R,S)- or (R,S,S,R)-5, and the electrophile
(S,S)-7 was added. Oxidation to remove the chromium led
to samples of (Sinner,Souter)-9 and (Rinner,Souter)-9 (Scheme 2).
Repetition of the reactions using electrophile (R,R)-7 in
conjunction with (S,R,R,S)- or (R,S,S,R)-5 gave samples of
(Sinner,Router)- and (Rinner,Router)-9, respectively, in 32% and
55% yield.9 (The NMR spectra of the isomers of 9 indicated
impurities of ca. 10%).
Figure 1. Homochiral dendrimer 1 and heterochiral dendrimer 2.
by CD spectroscopy. The chiroptical effect of L-chiral units
in the outer shell did not completely eliminate that of D-chiral
units in the inner shell, and it was concluded that the outer
chiral layer was chiroptically slightly different from the inner
layer.6 In a second study, dendrimers prepared from 1,1′-
binaphthol units of different configuration and linked by
amides were compared. CD and NMR studies revealed
differences between the homochiral and heterochiral isomers
that suggested that in the homochiral dendrimer the N-H
groups of the amides form hydrogen bonds that lead to a
different conformation of the molecule than in the hetero-
chiral dendrimer.7
We wish to report herein the synthesis of novel polyethers
in which the relationship between chirality placed near to
the center of the molecule (inner chirality) and chirality
placed at its edge (outer chirality) has a significant effect on
the properties of the molecule, as revealed by CD spectros-
copy. The synthesis draws on a chiral base-mediated reaction
that creates multiple stereocenters in a one-pot reaction with
high levels of stereochemical control.8
As expected, the UV absorption spectra of the four
stereoisomers were effectively identical (Figure 2, upper
(6) Chow, H.-F.; Mak, C. C. J. Chem. Soc., Perkin Trans. 1 1997, 91.
(7) Lellek, V.; Stibor, I. J. Mater. Chem. 2000, 10, 1061.
(8) (a) Castaldi, M. P.; Gibson, S. E.; Rudd, M.; White, A. J. P. Angew.
Chem., Int. Ed. 2005, 44, 3432. (b) Castaldi, M. P.; Gibson, S. E.; Rudd,
M.; White, A. J. P. Chem. Eur. J. 2006, 12, 138.
(9) The four stereoisomers of 9 were characterized by mp, 1H NMR,
13C NMR spectroscopy, mass spectrometry, elemental analysis, and UV
and CD spectroscopy.
3488
Org. Lett., Vol. 9, No. 18, 2007