Angewandte
Communications
Chemie
oligo-1,2-naphthylenes are sufficiently restricted in rotation
to form discrete stereoisomers, even well above room
temperature.
Motivated by these results, we became intrigued by the
possibility of assembling oligo-1,2-naphthylenes with more
than one element of axial chirality. A third building block was
added to ternaphthalene in 79% yield and with 95:5 enantio-
face discrimination (Scheme 4). The diastereoisomers (R,aS)-
of the end group, two rotamers were detected by NMR
spectroscopy, thereby serving as a gauge for interactions
operative between the oligomer units. Smaller congeners
display a balanced distribution, whereas atropodiastereomer
21 with a parallel arrangement of the first and the fourth
naphthalene groups shows a preference for one of the
rotamers (for 8, 9, and 20 = 1.0:1.1; for 21 = 1.0:1.7; for 22 =
[
9]
1.0:1.3).
X-ray crystallographic analysis of both quaternaphtha-
lenes confirmed the molecular arrangement of 21 and 22
[13]
(
Figure 1). A distinct right-handed helical secondary struc-
Figure 1. X-ray crystal structures of the 1,2-naphthylene atropodia-
stereoisomers 21 and 22 with opposite configuration of one of the two
chirality axes. Thermal ellipsoids are drawn at the 50% probability
[13]
Scheme 4. Synthesis of the two quaternaphthalene atropodiastereo-
isomers under substrate stereocontrol. a) 3, THF, 08C, d.r. 95:5, 79%;
level.
b) IBX, CHCl , 608C; c) LDA, THF, À308C!RT, d.r. 79:21 (22/21),
3
ture of 21 with three naphthalene units to each turn was
established. In the congested P-helix, the average biaryl
torsion angle is 668 and interatomic distances are as short as
2
9% over two steps. Compounds 9, 20, 21, and 22 were studied by
[
13]
X-ray crystallography. LDA: lithium diisopropylamide.
3
.3 . The inner benzene moieties are arranged analogous to
2
0 and (S,aS)-20 converge in the subsequent oxidation step.
ortho-phenylenes in the solid state, where self-organization
leads to the preferred helical coil. In contrast, quaternaph-
thalenecarbaldehydes 21 and 22 confirm that individual 1,2-
naphthylene diastereoisomers with a different relative con-
figuration of the chirality axes are isolable and configura-
However, the high selectivity provides an indication of the
well-defined structure of the ternapthalene (aS)-9. As
expected, based on the solid-state structure of (aS)-9 (fCC-
=
À1738), a selective re-face addition was obtained, as
CHO
[11]
[14]
confirmed by X-ray crystallographic analysis of (R,aS)-20.
tionally stable at room temperature.
After in situ double oxidation, we explored the accessibility
and configurational stability of the quaternaphthalene atro-
podiastereoisomers. The arene-forming aldol condensation
was, therefore, performed under substrate stereocontrol
using LDA. Satisfyingly, both atropodiastereoisomers
In conclusion, we have developed an efficient assembly
approach for the selective synthesis of discrete oligo-1,2-
naphthylene stereoisomers. A mixed-metal species obtained
by a practical transmetalation strategy served as the building
block for the protecting-group-free introduction of naphthy-
lene precursor units to enable rapid chain elongation. The
arene-forming aldol condensation allowed a stereoselective
synthesis of structurally distinct isomers of ter- and quater-
naphthalenes. Enantiocontrol was achieved by using a natural
amino acid as catalyst, while the preparation of both
individual atropodiastereoisomers with two elements of
axial chirality was based on a substrate-controlled arene-
forming aldol condensation. The unique structure of oligo-
(
1,2’aS:1’,2’’aS)-21 and (1,2’aR:1’,2’’aS)-22 were formed with
a d.r. of 79:21. The stereoisomers could be effortlessly
separated by preparative TLC, and routine analysis could
be performed due to the typically high solubility of helical
arylenes. The absolute configuration of the compounds was
established by comparison of the measured and calculated
CD spectra of compounds 9, 21, and 22, which displayed
[12]
exceptionally strong Cotton effects.
[15]
Having prepared both discrete quaternaphthalene atro-
podiastereoisomers, we examined the differences in the ring
1,2-naphthylenes leads to full configurational stability at
room temperature. The shape, such as the P-helix secondary
1
[16]
current effects observed in the H NMR spectra to gain
structure,
is not encoded in the building blocks, but is
insight into their structures in solution. The aldehyde proton
transcribed from l-isoleucine with 95:5 enantioselectivity. As
a result of the well-defined molecular structure, we expect
that oligo-1,2-naphthylenes will serve as scaffolds to predict-
ably place substituents into a preferred spatial arrangement.
In ongoing studies, we are examining catalyst-controlled
of 22 experiences a strong characteristic shielding (d =
H
8
.0 ppm; Dd (21CHO-22CHO) = 2.0 ppm), while the naphtha-
H
lene signals of 21 were distributed over a range of 2.2 ppm
dH = 8.0–5.8 ppm). As a result of the lower ortho-substitution
(
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Angew. Chem. Int. Ed. 2016, 55, 2920 –2923