Trityl ethers: Molecular bevel gears reporting chirality through circular dichroism spectra

Full text of DOI:10.1002/anie.200902167

Angewandte
Chemie
DOI: 10.1002/anie.200902167
Chirality
Trityl Ethers: Molecular Bevel Gears Reporting Chirality through
Circular Dichroism Spectra**
´
Jacek Sciebura, Paweł Skowronek, and Jacek Gawronski*
Dedicated to Professor Kurt Mislow
The study of the fascinating static and dynamic stereochem-
istry of molecular propellers was launched by Mislow and co-
workers over 30 years ago and was followed by unprece-
dented intellectual and experimental efforts of other groups.[1]
It is generally agreed that triarylmethyl systems exist in
enantiomeric propeller structures in which all three aryl rings
of a given molecule have the same sense of twist, either P or
M (Scheme 1).
formational properties of the triphenylmethyl (trityl) group.
Trityl systems are apparently less suitable for dynamic NMR
studies because of the low energy barriers to stereoisomers
interconversion. The paucity of stereochemical studies is in
contrast to the importance of the trityl group in synthetic
chemistry. The trityl group attached to a heteroatom (O, S, N)
is widely used as a versatile, acid-labile protecting group for
hydroxy (e.g. in sugars and nucleosides), thiol, and amine
groups.[9] Trityl derivatives often show interesting properties,
either biomedical[10] or in designing supramolecular clus-
ters,[11] helical nanotubes,[12] stators,[13] and disulfide cages.[14]
We anticipated that the trityl ethers of chiral secondary
alcohols would act as molecular bevel gears (Scheme 2),
Scheme 1. Enantiomerization of the C3-symmetric triphenylmethane
propeller.
The transition structure (TS) of the enantiomerization of
the triarylmethyl group can be achieved by correlated
rotation of the rings.[2,3] Extensive dynamic NMR studies
have shown that except for certain special cases, triarylmethyl
derivatives with substituted phenyl or naphthyl rings[4] have a
rotational barrier sufficiently low to prevent separation of
residual (conformational) stereoisomers.[5] Although the
process of enantiomerization can in principle involve four
different pathways (zero-, one-, two-, and three-ring flip
paths), the two-ring flip pathway[6] is considered a general
rotational mechanism for C3-symmetric propellers.[7,8] Zero-
and one-ring flips are not seen as real pathways to enantio-
merization since side-to-side orientation of the aryl substitu-
ents in the transition state would contribute enormously to
the energy of the molecule (see Figure S1 in the Supporting
Information).
Scheme 2. Propeller (a) and bevel gear (b) models of triphenylmethyl
group.
transmitting chiral information from the alcohol to the trityl
system, enabling its ready deciphering by means of induced
circular dichroism within the electronic transitions of the
phenyl groups. This observation could then be confirmed by
comparison with the calculated structural models and their
corresponding calculated CD spectra. Despite its conceptual
simplicity, this type of study has not been undertaken until
now, although a few examples of optically active C3-symmet-
ric propellers have been reported.[15]
A brief literature survey of structures of triphenylmethyl
derivatives Ph3CX determined by X-ray diffraction showed
that while the derivatives with formal C3 symmetry (X = H,
+
Despite detailed stereochemical studies of elaborate
triaryl entities, surprisingly little is known about the con-
Me, Cl, NH3 ; Table 1) have indeed the structures of
[16]
molecular propellers (dihedral angles w1–w3
are of the
same sign), it is not true for the trityl ethers (X = OR), for
which we observe a breakdown of C3 symmetry; that is, the
two dihedral angles are of opposite sign to the sign of the
third.
To test this hypothesis, we examined the trityl derivatives
1–12 of representative chiral alcohols. They show surprisingly
strong, characteristic Cotton effect patterns in their CD
spectra, as a result of a preferred helicity of the trityl group
(Table 2).
´
[*] J. Sciebura, Dr. P. Skowronek, Prof. J. Gawronski
Department of Chemistry, A. Mickiewicz University
Poznan (Poland)
E-mail: gawronsk@amu.edu.pl
´
[**] This work was supported by a grant from the Ministry of Science and
Higher Education (no. N N204 056335). All calculations were
performed in the Poznan Supercomputing and Networking Center,
Poland.
The derivatives of S configuration (1–4, 6) at the carbinol
carbon atom give rise to a negative Cotton effect within the
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200902167.
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Table 1: Dihedral angles w1, w2, and w3 in Ph3CX structures determined
by X-ray diffraction.
derivative (11) of (À)-borneol, because of its bicyclic struc-
ture. The insensitivity of sign of the Cotton effects to
molecular conformation in the case of R,R-tartaric acid
derivatives 7 and 8 is notable.[17] The sensitivity of the trityl
probe to remote molecular chirality is illustrated with the
À
derivative of cholesterol 12. Although the C O bond is
flanked by the two CH2 groups, the signs of the Cotton effects
due to the trityl ether correctly follow the configurational
scheme mentioned above because of the stereodifferentiation
X
w1
w2
w3
Ref.
[19]
=
of the CH2 and the CH groups in the b position. Therefore,
H
À61
66
À51
62
À45
47
the trityl ethers constitute nearly ideal chromophores, supe-
rior to those previously reported,[18] for sensing chirality, that
is, the difference in bulkiness of the substituents at the nearby
chiral center. This is also the first example of using a
trichromophoric derivative for sensing molecular chirality at
one chiral center.
Molecular modeling, using a Monte Carlo search followed
by DFT structure optimization, was carried out for a few
achiral triphenylmethane derivatives Ph3CX of formal C3
symmetry and for representative chiral trityl ethers of
formal C1 symmetry (acyclic 1, monocyclic 10, and bicyclic
11). Ph3CX molecules are represented by single minimum
energy propeller conformers of C3 symmetry (w1 = w2 = w3),
and the dihedral angle w increases in the order X = H (538),
X = F (598), X = Cl (698), according to the size of substituent
X. In contrast, five conformers of 1, differing in the
conformation of the four-carbon-atom chain (T, GÀ, G+),
one conformer of 10, and two conformers of 11, all of C1
symmetry of the trityl group, were found within the 3 kcal
molÀ1 energy window (Table 3).
Me
Cl
À72
À66
À67
À73
À75
À56
69
À66
À58
À66
À72
À61
À54
À56
À59
À57
À60
À69
À53
40
[20]
[21]
NH3+ PhSO3
OEt
OCH(Me)Ph
[11]
[22]
[23]
À
5
Table 3: Calculated conformer population for trityl ethers 1, 10, and 11.
Chain con- Conformer
w1
w2
w3 Conformer type
formation population [%]
1a
1b
1c
1d
1e
T
55.5
17
15
6.5
6
À74
À79
56 À6
54 À23
MPM
MPM
PMP
MPM
PMP
G+
G+
GÀ
GÀ
79 À54
22
À77
54 À17
81 À54
25
Table 2: Selected CD (De [nm]) and UV data (e [nm]) for chiral trityl
ethers (in cyclohexane).
MPM/PMP=79:21
De [nm]
e [nm]
10
>99
73 À56
5
PMP
1
2
3
4
5
6
7
8
À3.8 (208)
À5.4 (205)
À9.8 (205)
À7.6 (204)
7.2 (209)
À6.6 (210)
27.5 (205)
66.4 (203)
6.0 (210)
16.7 (194)
17.4 (194)
40.2 (195)
8.6 (195)
À21.4 (194)
41.7 (196)
À40.4 (193)
À81.7 (191)
À42.2 (196)
À80.4 (194)
36.4 (193)
13.5 (197)
84500 (193)
90900 (195)
80600 (193)
78400 (194)
74300 (193)
82000 (195)
75000 (194)
103000 (193)
73600 (192)
71700 (193)
79600 (193)
85300 (192)
11a
11b
76.5
23.5
À79
55 À25
MPM
PMP
76 À57
15
MPM/PMP=76.5:23.5
With respect to the helicity of the trityl group, only two
9
types of conformers were found, MPM (two w angles
negative, one positive) and PMP (two w angles positive,
one negative). One of the equal-sign dihedral angles w is large
(above 608), the other is small (less than 308), and the opposite
sign w angle is around 558 (see Figure S2 in the Supporting
Information). The calculated CD spectra for the separate
conformers of 1, 10, and 11 are distinct with regard to their
helicity, either MPM or PMP, and population-averaged
calculated CD spectra show satisfactory agreement with the
10
11
12
25.6 (208)
À15.8 (203)
À4.7 (217)
1Lb transition range (ca. 225 nm) and a negative CD couplet
within the strong B band (195–210 nm), the opposite being
true for R configuration (5, 7–10). The only exception is the
1
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experimental ones (see Figures S3 and S4 in the Supporting
Information).
stereoisomers of triarylmethanes and related systems, such as
helical trityl-substituted isotactic polymers.[24]
An additional benefit of the analysis of chirality trans-
mission from the chiral atom to the trityl group through the
difference of bulkiness of the L and M groups is the possibility
of correlation of the pattern of the CD spectrum with the
absolute configuration (Figure 1). In the cases studied herein
Received: April 22, 2009
Revised: July 6, 2009
Published online: August 17, 2009
Keywords: chirality · circular dichroism ·
.
configuration determination · Cotton effects
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À
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undergo virtually unhindered dynamic gearing through a
transition state of Cs symmetry, we were able to observe
residual stereoisomerism in trityl ethers by the combined use
of CD spectra and computational methods. Trityl ethers
behave as molecular bevel gears to sense and report chirality.
It is worth mentioning that trityl ethers have a very favorable
dissymmetry factor (De/e up to 10À3) for CD measurements.
Our finding opens new possibilities of using CD spectroscopy
as a tool for sensing dynamic equilibria of chiral residual
À
[16] Dihedral angles w1–w3 are defined by the nearest Cipso Cortho
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´
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´
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