G. Haberhauer et al.
height was fixed at 0.4 eV and the resulting intensity of the
combined spectrum was scaled to the experimental values
(Figure 5). As there are only a few chromophoric groups in
phosphane oxide 1, simulation of the CD spectra in the
region from 190 to 300 nm using TD-DFT should provide
quite precise results.
suppressed by the C2-symmetric scaffold. Kinetic control
must take place during alkylation, so that just (MMM)-1 is
present in solution.
Thus, we were able to transfer chirality during an alkyla-
tion reaction from a C2-symmetric chiral cyclopeptide to a
triphenyl phosphane oxide and fix its conformation by kinet-
ic control. Freezing of conformation is possible here without
overloading the phenyl groups with bulky substituents. This
concept should make it possible to easily prepare quantities
of configurationally stable stereoisomeric propellerlike com-
pounds.
Experimental Section
General remarks: All chemicals were of reagent grade and used as pur-
chased. Reactions were monitored by TLC analysis on silica gel 60 F254
thin-layer plates. Flash chromatography was carried out on silica gel 60
(230–400 mesh). 1H and 13C NMR spectra were measured on Bruker
Avance DMX 300, DRX 500 and DRX 700 spectrometers. The spectra
were referenced to deuterated solvents, indicated in parentheses in the
analytical data. HRMS spectra were recorded with a Bruker BioTOF III
Instrument. IR spectra were measured on a Varian 3100 FT-IR Excalibur
Series spectrometer. UV and CD absorption spectra were taken with a
Jasco J-815 spectrophotometer.
Figure 5. CD spectra of (MMM)-1 (blue), (PPP)-1 (green), and (MP)-1
(red) calculated with TD-DFT-PBE1PBE/6-31G* in acetonitrile as sol-
vent.
Phosphane oxide 1: Clamp 2 (10 mg, 0.018 mmol) and cesium carbonate
(59 mg, 0.180 mmol) in anhydrous acetonitrile (30 mL) were heated at
908C for ten minutes. Bis[m-(bromomethyl)phenyl]phenylphosphane
oxide (25 mg, 0.048 mmol) in anhydrous acetonitrile (5 mL) was added
and the mixture was heated to reflux for one hour. After cooling to room
temperature ethyl acetate and water were added and the aqueous layer
was washed twice with ethyl acetate. The organic layers were combined,
dried over MgSO4 and the solvent was removed. Column chromatogra-
phy of the residue on silica gel (DCM/EtOAc/MeOH 75/25/5) provided
phosphane oxide 1 as a white solid (8 mg, 35%). M.p.>3008C; 1H NMR
(500 MHz, CDCl3, 258C): d=7.71–7.67 (m, 1H; Har), 7.58–7.52 (m, 8H;
Comparison of the experimental and calculated spectra
verifies that (MMM)-1 is the actual conformation: The mea-
sured CD spectrum shows a very positive Cotton effect at
200 nm and two negative Cotton effects at 225 and 250 nm.
The transition from one minimum to the other proceeds
over a flat maximum at 235 nm with a negative value of De
(ꢀÀ25mÀ1 cmÀ1). In the calculated spectra the curve pro-
gressions are quite similar for all three isomers, but only the
curve of (MMM)-1 has a maximum at 235 nm with a nega-
tive De value. Like in the measured spectrum of (MMM)-1
the calculated maximum is À25mÀ1 cmÀ1. In accordance to
the NMR data it can therefore be assumed that 1 is exclu-
sively present as (MMM)-1.
Har), 7.47–7.44 (m, 2H; Har), 7.16 (d, 3J
(d, 3J(H,H)=10.1 Hz, 1H; NH), 6.79 (d, 3J
6.66–6.62 (m, 3H; NH, Har), 5.29 (d, 2J
(H,H)=16.0 Hz, 1H; CH2), 5.10
(d, 2J
(H,H)=16.5 Hz, 1H; CH2), 5.08–5.06 (m, 1H; NHCHCH), 5.03–
5.00 (m, 2H; NHCHCH), 4.97 (d, 2J
(H,H)=16.0 Hz, 1H; CH2), 4.80 (d,
2J
(H,H)=16.5 Hz, 1H; CH2), 4.54–4.48 (m, 2H; NHCHCH), 2.39 (s, 3H;
imidazole CH3), 2.34–2.28 (m, 2H; CHCH(CH3)2), 2.28–2.22 (m, 2H;
CHCH(CH3)2), 2.15 (s, 3H; imidazole CH3), 1.15–1.11 (m, 12H; CH-
(CH3)2), 0.94 (d, 3J (CH3)2), 0.91 (d, 3J
(H,H)=6.8 Hz, 3H; CH (H,H)=
6.8 Hz, 3H; CH (H,H)=6.8 Hz, 3H; CH(CH3)2),
(CH3)2), 0.84 (d, 3J
0.81 ppm (d, 3J (CH3)2); 13C NMR (125 MHz,
(H,H)=6.8 Hz, 3H; CH
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
A
E
N
ACHTUNGTRENNUNG
Conclusion
A
R
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
CDCl3, 258C): d=171.8, 171.7, 162.7, 162.5, 146.5, 145.4, 136.0, 135.9,
133.7, 133.6, 133.1, 132.5, 132.2, 132.1, 131.8, 131.5, 131.1, 131.0, 130.7,
130.6, 130.3, 130.1, 129.3, 128.2, 60.2, 51.9, 51.4, 47.5, 34.2, 30.8, 19.9, 19.4,
19.2, 19.0, 17.8, 11.3, 11.2 ppm; 31P NMR (203 MHz, CDCl3, 258C): d=
Triaryl phosphane oxide 1 exhibits exclusively one confor-
mation with frozen helicity and an MMM configuration in
solution. These results can be explained with two hypothe-
ses: The MMM isomer could be stabilized by more than
18 kJmolÀ1 in contrast to the other diastereomers, so that
MMM exists for thermodynamic reasons. Another possibili-
ty is a kinetically stabilized MMM isomer, which means that
an epimerization does not take place because of activation
barriers that are too high.
According to DFT calculations the MMM conformation
of 1 is energetically the least stable with a difference of only
7.5 kJmolÀ1 to the most stable conformer MP. As a conse-
quence the stabilization of the configuration cannot be ex-
plained by thermodynamics. Thus (MMM)-1 must be kineti-
cally preferred and the inversion of helicity is effectively
~
28.91 ppm; IR (KBr): n=3377, 3048, 2963, 2928, 2871, 1650, 1503, 1467,
1260 cmÀ1; UV/Vis (MeOH): l (loge)=201 nm (4.81); HRMS (ESI):
calcd for C48H59N8O5P [M+H]+: 859.4419; found 859.4491.
Bis[m-(bromomethyl)phenyl]phenylphosphane oxide (3): BisACHTUNGTRENNUNG(m-tolyl)-
phenylphosphane oxide (1.00 g, 3.28 mmol), N-bromosuccinimide (1.23 g,
1.23 mmol), and a catalytic amount of azoisobutyronitrile in tetrachloro-
methane (30 mL) were heated to reflux and irradiated with UV light for
nine hours. After removal of the solvent and column chromatography of
the residue on silica gel (hexane/EtOAc 1/1) phosphane oxide 3 was ob-
tained as
a
yellowish solid (0.92 g, 61%). M.p. 1128C; 1H NMR
(500 MHz, CDCl3, 258C): d=7.76–7.73 (m, 2H; Har), 7.68–7.64 (m, 2H;
Har), 7.61–7.59 (m, 2H; Har), 7.58–7.52 (m, 4H; Har), 7.50–7.43 (m, 5H;
Har), 4.47 (s, 4H; CH2) ppm; 13C NMR (125 MHz, CDCl3, 258C): d=
138.7, 133.6, 133.5, 133.0, 132.5, 132.4, 132.2, 132.1, 19.3, 128.9, 128.8,
8646
ꢃ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 8643 – 8647