Angewandte
Chemie
DOI: 10.1002/anie.201201891
NMR Spectroscopy
Polyacetylenes as Enantiodifferentiating Alignment Media**
Nils-Christopher Meyer, Alexis Krupp, Volker Schmidts, Christina M. Thiele, and
Michael Reggelin*
The availability of residual dipolar couplings (RDCs) mea-
sured in weakly aligned media has had a major impact on the
structural characterization of dissolved (chiral) molecules by
NMR spectroscopy.[1] This has been and still is especially true
for biomacromolecules[2] but more recently, the field has seen
a rapidly increasing interest in the application of RDCs to
solve structural problems for small molecules, too.[1e,3] This, at
first sight surprising fact, is by no means a back-extension,
because the molecules under investigation pose problems
being absent in the above-mentioned biopolymers. In contra-
diction to the latter many small molecules contain stereogenic
units of unknown relative and absolute configuration. Given
the fact that configurational analysis is always a problem of
conformational analysis at the same time, the simultaneous
treatment of both structural aspects is a necessity to solve the
stereochemical problem exhaustively.[4]
With the advent of RDCs as a new NMR parameter
containing distance and angle information the scope of NMR-
based stereochemical analysis has been broadened consider-
ably. This is mainly because of the fact that RDCs deliver
conformationally relevant information without the need for
parametrization as is the case for the evaluation of scalar
couplings.[5] Moreover, RDCs are global parameters not
relying on short-range interactions like cross-relaxation
(nuclear Overhauser effect, NOE)[6] or cross-correlated
relaxation.[7]
typical organic molecules being insoluble in water. On the
other hand if the determination of the absolute configuration
of a chiral, nonracemic water-insoluble compound is the goal
of the investigation, it is necessary to orient the analyte in an
enantiodifferentiating manner. This in turn is possible only if
the alignment medium is itself chiral and of uniform config-
uration. The number of media fulfilling these criteria is still
extraordinary small.[1e] As far as chiral LLC phases are
concerned, only the homopolypeptide-based LLC phases
derived from poly-g-benzyl-l/d-glutamate (PBLG/PBDG),
poly-g-ethyl-l-glutamate (PELG/PEDG), and poly-e-carbox-
ybenzoyl-l/d-lysin (PCBLL/PCBDL)[8] as well as a recently
introduced polyguanidine[9] are known to meet the described
needs. Moreover, Luy and co-workers have shown that gelatin
cross-linked by accelerated electrons (eÀ-gelatin) allows for
the distinction of enantiomers in DMSO and DMSO/D2O
mixtures at temperatures up to 608C.[10]
Despite our encouraging results with the polyguani-
dines,[9] we decided to look for alternative helically chiral
polymers capable of forming LLC phases. This decision was
driven by a number of drawbacks associated with the
polyguanidines. First of all the linewidths of the NMR signals
from the analyte are rather large which hampers a precise
determination of RDCs. Furthermore, the induced alignment
is too strong which may lead to strong coupling artifacts.
Finally, the purification of the noncrystalline carbodiimide
monomers suffers from decomposition during chromatogra-
phy.
A precondition for the measurement of RDCs, as
anisotropic NMR parameters, is to partially orient the analyte
with respect to the magnetic field (weak alignment: RDC
amounts approximately 10À3 of the maximum dipolar cou-
pling). This can be done either by stretched polymer gels
(SAG = strain-induced alignment in a gel) or by dissolving the
compound in a lyotropic liquid-crystalline (LLC) phase.[3a,b,l]
In the last years considerable progress has been made in the
field of these orienting or alignment media especially for
Within the family of helically chiral polymers[11,12] the
amino-acid-stabilized polyisocyanides[13] and polyacety-
lenes[14] look most promising. Both polymer types are
known to form LLC phases[13c,d,14f,g,h] in a number of organic
solvents and they are characterized by large persistence
lengths[13d,14h] (depending on the solvent) which should reduce
the critical concentration for the phase transition.[15] More-
over, the synthesis of the corresponding monomers is
straightforward and their transition-metal-induced polymer-
ization works efficiently with a high tolerance for functional
groups.[14e,16] In this contribution we would like to describe the
suitability of the valine-derived polyacetylene p1 and its
enantiomer p2 as alignment media.
[*] Dipl.-Chem. N.-C. Meyer, Dipl.-Ing. A. Krupp, Dipl.-Ing. V. Schmidts,
Prof. Dr. C. M. Thiele, Prof. Dr. M. Reggelin
Technische Universitꢀt Darmstadt
Clemens Schçpf Institut fꢁr Organische Chemie und Biochemie
Petersenstrasse 22, 64287 Darmstadt (Germany)
E-mail: re@punk.oc.chemie.tu.darmstadt.de
The synthesis of monomer 1 was achieved in three steps
starting from 4-iodobenzoic acid ethyl ester 2 and valine 3
(Scheme 1; for a detailed description see the Supporting
Information).[17]
Homepage: deepthought.oc.chemie.tu-darmstadt.de
[**] The authors would like to thank the German Research Council
(DFG) for the funding of the Research Unit FOR 934 (grant numbers
RE 1007/7-1 and TH 1115/3-1).
According to the work of Okoshi and Yashima[14f,18] the
polymerization of 1 was initiated by [Rh(nbd)Cl]2 delivering
polymer p1 as a yellow solid (nbd = norbornadiene). This
polymerization reaction was repeated three times whereby
a total of four different polymer samples (p1a, p1b, p1c, and
Supporting information for this article, including experimental
details for the monomer, polymer, the phase preparations, and the
sample compositions as well as the definitions of the tensor
comparison sets and the tensor calculations, is available on the
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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