Communications
tures: 1) the pronounced preference of the piperidine ring to
to (E)-4a–c could be induced thermally or by irradiation with
light (l ꢀ 400 nm). Using preparative irradiation, (Z)-4a–c
containing only minor amounts of residual E isomer were
isolated and characterized. In the case of 4b, both switching
states of the system could be characterized by single-crystal
X-ray structure analysis (Figure 2).[12] Owing to the presence
of the spiro junction, the isobenzofuran-1-one moiety is
oriented perpendicular to the plane of the piperidine ring,
which adopts a chair conformation with the N-tert-butyl group
occupying an equatorial position. Taking the van der Waals
radii into account, inspection of the structure of (E)-4b shows
that the piperidine lone pair is well shielded by one of the
equivalent tert-butyl groups of the 3,5-di-tert-butylphenylazo
fragment (Figure 2, bottom left). On the contrary, in the
corresponding isomer (Z)-4b flipping of the 3,5-di-tert-butyl-
phenylazo fragment due to E!Z isomerization renders the
piperidine lone pair much more accessible (Figure 2, bottom
right).[13]
adopt a chair conformation with the N-alkyl substituent in an
equatorial position,[11] 2) the spiro junction, which enables the
rigid and orthogonal positioning of the photochromic azo-
benzene moiety, and 3) the steric bulk of the symmetrical 3,5-
disubstituted phenylazo substituent and its position ortho to
the spiro center. We envisioned that irradiation of the
shielded, inactive E isomer, corresponding to the “resting
state”, would trigger photochemical E!Z isomerization,
accompanied by a large structural change and thereby
revealing the active Z isomer, in which the lone pair of
electrons on the N atom becomes sterically accessible (shown
for 4b in Figure 2).
These structural differences between the interconvertible
isomers are reflected in differences in chemical reactivity. The
basicity of the deshielded Z isomers is increased by almost
one order of magnitude as compared to the shielded
E isomers as shown by titration experiments with trifluoro-
methanesulfonic acid in acetonitrile solution using Neutral
Red as the reference base (Table 1). The higher basicity of the
Z isomer can be attributed to the increased thermodynamic
stability of [(Z)-4–H]+ relative to [(E)-4–H]+, but also to
kinetic factors associated with the enhanced accessibility of
the basic site. These kinetic factors will be particularly
important for larger electrophiles. Importantly, as protona-
tion was found to have a negligible influence on the photo-
chemical and thermal isomerization behavior of 4,[10] the
basicity function can be decoupled from the switching
function.
Figure 2. Light-induced reversible conversion of the less-reactive
E isomer (E)-4b, with a sterically shielded basic/nucleophilic lone pair
of electrons on the piperidine N atom (left), into the accessible and
hence more reactive Z isomer by E!Z isomerization of the spiro-
linked azobenzene substituent. Space-filling structures (C dark gray, H
light gray, O red, N blue) are derived from single-crystal X-ray structure
analysis of (E)-4b (bottom left, CCDC 686676) and (Z)-4b (bottom
right, CCDC 686677).[12]
In a first proof of concept, we exploited the different
basicities of the two switching states to photocontrol con-
version in the general-base-catalyzed nitroaldol reaction
(Henry reaction).[14] The lowbackground rate of the non-
catalysed Henry reaction facilitates kinetic analysis. In a
[D8]THF solution, 4-nitrobenzaldehyde (5) was treated with
excess nitroethane (6) in the presence of 10 mol% catalyst
4a–c and the evolution of the mixture of syn and anti
Irradiation of (E)-4a–c with light of wavelength 365 nm
led to rapid photoisomerization to yield almost quantitatively
the corresponding isomers (Z)-4a–c with remarkably long
thermal half-lives at room temperature (Table 1). Reversion
1
nitroaldol products 7 was monitored in situ using H NMR
spectroscopy (Table 1, Figure 3).[10,15] In all cases, the use of
the Z isomer led to faster product formation than that
observed with the E isomer. Although the on/off ratio,
defined as the quotient of the rate constants with the Z and
E isomers is moderate for the sterically least hindered catalyst
4a, this ratio can be improved to significant values by
appropriate molecular design based on the introduction of
sterically more demanding substituents R and R’. The
Table 1: Photochemical, kinetic, and thermodynamic data for the
piperidine bases 4a–c.
PSS[a]
(Z/E)
t1/2
[h]
koff
kon
krel
(kon/koff)
DpKa[e]
[b]
[c]
[d]
[10ꢁ6 sꢁ1
]
[10ꢁ6 sꢁ1
]
4a
4b
4c
90:10
90:10
>90:10
268
286
466
4.96
0.963
0.391
21.5
12.7
13.9
4.3
13.2
35.5
–
0.8
0.7
=
involvement of the much less basic N N group can be
excluded on the basis of experiments with azobenzene itself as
the catalyst: No product formation was observed.[10] Under
the reaction conditions employed, the Henry reaction is
known to proceed by general base catalysis, whereby the rate-
limiting step is the deprotonation of the CH-acidic nitro-
alkane by the tertiary amine.[14b] Therefore, the barrier for
proton abstraction by the general base catalyst locked in its
[a] Photostationary state (PSS) obtained by irradiation at 365 nm.
[b] Half-life of the Z isomer, measured at 208C. [c] Rate constant of
Henry reaction using pure E isomer (Figure 3). [d] Rate constant of
Henry reaction extrapolated to 100% Z isomer (Figure 3). [e] Difference
of pKa values, i.e. pKa(PSS)ꢁpKa(E), obtained from titration with
trifluoromethanesulfonic acid using Neutral Red as reference base.
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 5968 –5972
Peters, Maike V.
