696
(a)
(b)
No H-bond
No H-bond
MeO
Ar
N
Ar
N
(R,R)-1b
MeO
Ar
Ar
OMe
OMe
1)NaH
2)MeI
ICH2CH2CH2I
N
N
(R,R)-3b2+ (I-)2
(R,R)-2b
Figure 1. CD spectra of (a) (R,R)-1b (1.5 © 10¹5 M) and (b)
(R,R)-2b (2.0 © 10¹5 M) in a series of CH2Cl2-CH3OH mixed
solvent with a different ratio (CH3OH v/v %: red 0, orange 25,
green 50, blue 75, and black 90).
Scheme 3.
cases, the first fractions are dextrorotatory [(+)-1],14,15 and their
circular dichroism (CD) spectra are similar to each other in the
sense that they exhibit positive Cotton effects for the first band
(300-310 nm) in CH2Cl2 (Figure S1).14,16 Their configurations
at C5 and C6 are determined to be R,R by derivatization of
(+)-1b into dimethoxydiazepinophenanthrolinediium diiodide
(a)
(b)
(R,R)-(+)-3b2+(I )2 (Scheme 3), which was analyzed carefully
¹
by X-ray17 at a low temperature considering anomalous
dispersion [Flack parameter » = ¹0.02(3)] (Figure S2).14 Crys-
tallographic study was also conducted for (R,R)-(+)-1c (P1,
Z = 4),17 which adopts P-helical geometry for the dihydrophen-
anthroline unit (Figure S3) as in the cases of (R,R)-(+)-1a and
-1b crystals determined previously.13
Figure 2. (a) CD spectral changes of (R,R)-1b (2.3 © 10¹5 M)
upon addition of TsOH in CH2Cl2 (TsOH equiv: red 0, orange
0.25, green 0.50, blue 0.75, and black 1.0). (b) CD spectral
changes of (R,R)-1b¢H+ (1b: 2.2 © 10¹5 M; TsOH: 8.8 ©
10¹5 M) in a series of CH2Cl2-CH3OH mixed solvent with a
different ratio (CH3OH v/v %: red 0, orange 1, green 5, blue 10,
and black 25).
According to a conformational search on (R,R)-1b by using
the Conflex program,18 the P-helical structure is found as the
energy-minimized conformer, for which several variants exist
within a narrow range of energy (0.1 kcal mol¹1).19 The TD-DFT
calculations indicated that they all exhibit positive Cotton effects
for the first band (300-310 nm) (Figure S4),14 showing that
(R,R)-1b in CH2Cl2 adopts P-helicity primarily. Intramolecular
H-bonding in (R,R)-1b would be the important factor for the
observed conformational preference since a similar calculation
on the dimethoxy derivative (R,R)-2b showed that the M-helical
structure is dominant, for which the negative Cotton effect was
calculated for the first band (Figure S5).14 This prediction is
in accord with the experimental CD spectrum of (R,R)-2b
(-ext = 303 nm, ¦¾ = ¹11.0 in CH2Cl2). The above results
show that O-methylation of (R,R)-1b induces conformational
switching from P- to M-helicity by prohibiting the intra-
molecular H-bond in (R,R)-2b, which is accompanied by the
change in the sign of Cotton effects from positive to negative at
the 300-310 nm region.
Not only the chemical modification of hydroxy groups but
also simple addition of protic solvent could cleave the intra-
molecular H-bond (Scheme 1), which is evidenced by the CD
spectra of (R,R)-1b measured in a series of CH2Cl2-CH3OH
mixed solvent with a different ratio (Figure 1a). Thus, an
increase in CH3OH proportion weakened the positive ellipticity
for the first band (300-310 nm), suggesting that some portion of
(R,R)-1b changed its helicity from P to M to give a mixture of
(P)- and (M)-(R,R)-1b with P-helicity in major. Similar behavior
was also observed in other diols (R,R)-1a, -1c, and -1d
(Figure S6),14 but the spectrum of dimethoxy derivative (R,R)-
2b remained unchanged irrespective of CH3OH proportion in
CH2Cl2-CH3OH (Figure 1b). Since the spectrum of (R,R)-1b
measured in CH3CN is identical to that in CH2Cl2, the decisive
factor for switching the helicity is not the polarizability of
solvent but the formation of intermolecular H-bonds between
protic solvent and the hydroxy groups in 1.
Halochromic response was then studied by salt formation of
diol (R,R)-1b at the dihydrophenanthroline unit with Brønsted/
Lewis acid. According to NMR analysis, monoprotonation
occurs exclusively at the dihydrophenanthroline unit upon
gradual addition of TsOH in CDCl3 (Figure S7).14 Similar
addition to a CH2Cl2 solution of (R,R)-1b caused a red-shift of
the first band from 300-310 to 330 nm in the UV spectrum
(Figure S8).14 Protonation also induced a red-shift of ellipticity
in the CD spectrum without changing the sign of Cotton effects
(Figure 2a), indicating that P-helicity is still preferred for (R,R)-
1b¢H+ in CH2Cl2.
The protic solvent also affects the helicity preference of
(R,R)-1b¢H+ as shown in Figure 2b. A much smaller amount of
CH3OH is sufficient (5%) to induce the maximum effect, and the
proportion of M-comformer is larger than the unprotonated
(R,R)-1b as evidenced by the negative sign of the Cotton effect
for the first band. Such observation suggests that cleavage of
intramolecular H-bond by CH3OH is facilitated by protonation
of the dihydrophenanthroline unit, which can be accounted for
by considering planarization of the helical ³-system upon
protonation.21 That is, larger separation between two equatorial
hydroxy groups at C5 and C6 is expected in (P)-(R,R)-1b¢H+
than in unprotonated (P)-(R,R)-1b, which would be responsible
for weakening the intramolecular H-bond between hydroxy
groups upon protonation at the N-ligand.
Chem. Lett. 2010, 39, 695-697
© 2010 The Chemical Society of Japan