Enantiodivergent Steglich rearrangement of O-carboxylazlactones catalyzed by a chirality switchable helicene containing a 4-aminopyridine unit

Article abstract of DOI:10.1039/c6sc02646j

A pseudo-enantiomeric pair of optically switchable helicenes containing a catalytic 4-N-methylaminopyridine (MAP) bottom unit and a C₂-symmetric, (10R,11R)-dimethoxymethyl-dibenzosuberane top template was synthesized. They underwent complementa

Full text of DOI:10.1039/c6sc02646j

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Enantiodivergent Steglich Rearrangement of O-
Carboxylazlactones Catalyzed by a Chirality Switchable Helicene
Containing a 4-Aminopyridine Unit
Received 00th January 20xx,
Accepted 00th January 20xx
Chien-Tien Chen,* Cheng-Che Tsai, Pei-Kang Tsou, Gou-Tao Huang, and Chin-Hui Yu*
DOI: 10.1039/x0xx00000x
A pseudo-enantiomeric pair of optically switchable helicenes containing a catalytic 4-N-methylaminopyridine
(MAP) bottom unit and a C2-symmetric, (10R,11R)-dimethoxymethyl-dibenzosuberane top template was
synthesized. They underwent complementary photoswitching at 290 nm (P/M’, <1/>99) and 340 nm (P/M’,
91/9) and unidirectional, thermo-rotation at 130 oC (P/M’, >99/<1). They were utilized to catalyze
enantiodivergent Steglich rearrangement of O- to C-carboxylazlactones, with formation of either
enantiomers with up to 91% ee (R) and 94% ee (S), respectively.
www.rsc.org/
The development of enantiodivergent catalysts has garnered scaffold.9 Photoswitchable catalysts that are capable of modulating
significant interests in recent years, because it allows for the reaction enantioselectivity [from 50% ee (S,S) to 5% ee (S,S)] have
production of either enantiomerically enriched compounds based on been established.10 However, as compared to enantiodivergent
a single chiral catalyst.1 To date, several enantiodivergent catalytic catalyses, the catalytic processes based on lightꢀ or heatꢀmodulated,
systems under various conditions have been reported, in which the pseudoꢀenantiomeric catalysts remain challenging. Towards this end,
chiral environment of the complementary transition states can be herein we report a highly selective, enantiodivergent Steglich
tuned. For instance, reaction temperatures,2 solvent effects,3 achiral rearrangement of Oꢀcarboxylazlactones by using a nucleophilic
coꢀcatalysts,4 structural modifications of functional substrates,5 and helical catalyst with an embedded MAP unit, whose chirality can be
different coordinating metal ions6 were found to facilitate switched.
enantiodivergent catalyses with good to high enantioselectivities
Asymmetric Steglich rearrangement, an enantioselective Oꢀ to Cꢀ
(89ꢀ97 % ee). Nevertheless, such specific conditions may not be carboxyl group transfer reaction, is a reliable method for the
suitable for all desired transformations and substrate scopes. In construction of a quaternary stereogenic center. Until now, a variety
marked contrast, enantiodivergent catalyses using pseudoꢀ of chiral nucleophilic catalysts for asymmetric Steglich
enantiomers that can be interconverted by an external stimulus rearrangements have been developed with remarkable successes. For
constitutes
a
more practical approach. For example, the example, planarꢀ and centralꢀchiral derivatives of 4ꢀ
enantiodivergent hydrosilylation of styrenes was first accomplished dimethylaminopyridine (i.e. DMAP) were first introduced by Fu,11
by Suginome and coꢀworkers by using a polymerꢀbased chiral Richards,12 and Vedejs.13 Recently, easily accessible, Cꢀ3
catalyst, whose helical chirality depended on solvent polarity and functionalized DAMPs were described by Poisson,14 Mandai and
attributes.7 Moreover, Canary and coꢀworkers demonstrated an Suga.15 In addition, chiral tetrahydropyrimidineꢀbased isothioureas
enantiodivergent, conjugate addition of diethyl malonates to and chiral Nꢀheterocyclic carbenes (i.e. NHC) utilized by Smith,16
nitrostyrene [up to 70% ee (R) and 72% ee (S)] by using redoxꢀ chiral ammonium betaines employed by Ooi,17 and chiral bicyclic
reconfigurable copper(I/II) complexes.8 In addition, Feringa and coꢀ imidazoles designed by Zhang18 were developed with better
workers described
a
temperatureꢀmodulated, lightꢀtriggered enantiocontol or broader substrate scope. In these distinguished
enantiodivergent Michael addition [up to 54% ee (R) and 50% ee works, however, only one of two possible enantiomers in the
(S)], Henry reaction [up to 72% ee (R) and 42% ee (S)], and Pdꢀ products could be obtained, except in Smith’s work using pseudoꢀ
catalyzed allylic desymmetrization [up to 88% ee (S,R) and 86% ee enantiomeric isothioureas prepared from different chiral sources.
(R,S)], utilizing
a thiourea/DMAP hybrid organocatalyst or With respect to the requirement of pharmacological study, a feasible
biphosphine ligand employing helically chiral molecular motor access to both enantiomeric Cꢀcarboxyazlactones should be
developed. In this study, we describe an enantiodivergent approach
to obtain both enantiomeric Cꢀcarboxylazlactones by using
a
Department of Chemistry, National Tsing Hua University, No. 101, Section 2,
Kuang-Fu Road, Hsinchu 30013, Taiwan.
E-mail: ctchen@mx.nthu.edu.tw; chyu@mx.nthu.edu.tw.
chirality switchable nucleophilic helicene containing
aminopyridine unit.
a
4ꢀ
As part of our onꢀgoing researches on the C2ꢀsymmetric
dibenzosuberane (DBS)ꢀbased helicenes as conformationally
Electronic Supplementary
DOI: 10.1039/x0xx00000x
Information
(ESI)
available:
See
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Journal Name
flipable, chirochromic optical switches in liquid crystal materials and
In order to identify two distinctive irradiation wavelengths to
supramolecular organogels,19 we evaluated the feasibility of their induce photochemical switching between the two pseudoꢀ
uses in enantiodivergent catalysis. In this study, we synthesized a enantiomeric helicenes [i.e, (P)ꢀ1 and (M’)ꢀ1], their individual
new photoꢀswitchable and unidirectional thermoꢀrotable helicene 1, UV/Vis and difference spectra with complementary changes in the
whose
catalytic
activity
was
originated
from
4ꢀNꢀ extinction coefficient (ꢀε) at two given wavelengths should be
methylaminopyridine (i.e., MAP).20,21 Notably, the proximity of the identified. This information provides their relative abundance and
catalytic site (i.e., N7’) to the upper chiral DBS template facilitates thus the composition of the photostationary state (i.e., pss) at a given
the asymmetric discrimination in the pyridineꢀcentered activation irradiation wavelength to be assessed. The diastereomeric (i.e.,
event (Scheme. 1).
pseudoꢀenantiomeric) excess of the pss from irradiation at a given
23
wavelength (i.e., [de]pss
)
can often be directly determined by the
Previous works
This work
MeO
extinction coefficient difference under the conditions where the
photoisomerization quantum yields (ΦM’→P and ΦP→M’) for the both
processes are similar. Therefore, to induce efficient switching in a
highly diastereoselective (pseudoꢀeantiomeric in this system)
manner, irradiation should be targeted at regions with significant and
complementary differences in the extinction coefficients.
OMe
R
R
10
11
G
G
Cl
7'
Cl
X
N
Catalytic
unit
N
Me
R = CH3, OCH3, OC7H15
G = H, NHCOAr
X = H, Br, Ph
1
(10R, 11R, P)-
(a)
MeO
MeO
OMe
photo-switching
OMe
MeO
OMe
Scheme 1. Molecular design of chirality-switchable, helicene-based, 4-N-
methylaminopyridine (MAP) as an organocatalyst.
290 nm
<1:>99
(P)-1:(M)-1'
unidirectional
thermo-
rotation
130 o
xylene
C
Cl
Cl
Cl
Cl
Cl
The key synthetic steps towards the pyridineꢀincorporated
helicene (10R,11R,P)ꢀ1 (i.e., (P)ꢀ1) is shown in Scheme 2 (see SI for
details). Hydrazone 5, prepared from tꢀbutylꢀ1,2,3,4ꢀtetrahydroꢀ1,6ꢀ
Cl
CH2Cl2
N
N
N
340 nm
91:9
(P)-1:(M)-1'
N
N
N
(P)-1
(M)-1'
(P)-1
unidirectional
thermo-
130 oC
naphthyridineꢀ1ꢀcarboxylate in
3 steps, was converted to the
rotation
(c)
xylene
(b)
corresponding diazo compound by treatment with PhI(OCOCH3)2 at
ꢀ20 oC in a 1/1 mixture of DMF/CH2Cl2. Subsequent reaction of the
diazo compound with freshly prepared thioketone 4 afforded
(10R,11R,1’S)ꢀMOMꢀDBSꢀbased episulfide 3 in 48% isolated yield
as a single diastereomer. Support for the (S)ꢀabsolute configuration
at C1’ in 3 was obtained by circular dichroism (CD) analysis and
comparing its sign of specific optical rotation and exciton chirality
with those of analogous episulfides previously reported by us.19a,c
Stereospecific, reductive desulfurization of episulfide 3 with HMPT
at 0 oC gave helicene (P)ꢀ2 in 76 % isolated yield. Finally, reductive
0
min
120
100
80
60
40
20
0
-20
-40
-60
10 min
20 min
30 min
40 min
50 min
60 min
6000
5000
(P)-1
(M)-1'
(P)-1-(M)-1'
)
4000
3000
2000
(
290
1000
0
340
221
310
300
-1000
200 250 300 350 400
wavelength (nm)
400
wavelength (nm)
o
methylation of NꢀBoc (P)ꢀ2 with DIBAL in THF at 50 C furnished
Fig.
1 Control and monitor of helical chirality. (a) Complementary
the desired Nꢀmethyl (P)ꢀ1 in 80% yield without epimerization of the
helicene, as evidenced by HPLC analysis. The (P)ꢀform helical
chirality of 1 was confirmed by observing a negative exciton
chirality at 221 nm by CD analysis (see Fig. 1c).22
photoisomerization of helicenes (P)-1 and (M)-1’ in degassed CH2Cl2 (1 × 10-4
M) and unidirectional, thermorotation of (M)-1’ in xylene at 130 oC. (b) UV-
Vis and difference spectra of (P)-1 and (M)-1’ in degassed CH2Cl2 (1 × 10-4 M).
(c) Dynamic trace experiments with CD stacked plots before and after
irradiation of (P)-1 at 290 nm in degassed CH2Cl2 (1.0 × 10-4 M).
The photochemical switching experiments were carried out by
irradiating individual (P)ꢀ1 and (M)ꢀ1’24 in degassed CH2Cl2 under a
monochromator light source (Fig. 1a). The irradiation wavelengths
were set at the wavelengths of 290 nm and 340 nm with the largest
and complementary differences in the extinction coefficients which
were determined by using the UVꢀvis difference spectrum between
(P)ꢀ1 and (M)ꢀ1’ (Fig. 1b). Photochemical switching of (P)ꢀ1 was
first performed at 290 nm, which led to the exclusive formation of
(M)ꢀ1’ [(P)ꢀ1/(M)ꢀ1’, <1/>99)]. The relative composition of the
reaction mixture was monitored by HPLC on a Chiralcel AD column
until the pss was reached (see Fig. S1ꢀS3 in SI) with the detection
wavelength set at the isosbestic point (i.e., 310 nm) of (P)ꢀ1 and
(M)ꢀ1’. Photoisomerization of pure (M)ꢀ1’was then performed at 340
nm, which led to the predominant enrichment of (P)ꢀ1 [(P)ꢀ1:(M)ꢀ1’,
91:9]. The diastereomerically pure (P)ꢀ1 can be regenerated either by
MeO
OMe
MeO
10R
OMe
11R
MeO
OMe
HMPT:
P(NMe2)3
Cl
Cl
S
PhI(OCOCH3
)
2
4
5
S
Cl
Cl
Cl
Cl
Boc
N
1'S
N
N
N
N
N
R
NNH2
Boc
(i-Bu)2AlH
3
2
(P)- , R = Boc
(DIBAL)
(P)-1, R = Me
Scheme 2. Synthesis of (10R,11R,P)-helicene, (P)-1, bearing catalytic 4-N-
methylaminopyridine (MAP) lower template. HMPT stands for
hexamethylphosphorous triamide. DIBAL stands for diisobutylaluminum
hydride.
2 | J. Name., 2012, 00, 1-3
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unidirectional, thermoꢀrotation of the 91/9 [(P)ꢀ1:(M)ꢀ1’] mixture or of enantiocontrol indicated a complementary helical asymmetric
by unidirectional, thermoꢀrotation of pure (M)ꢀ1’ in pꢀxylene at 130 environment in the pseudoꢀenantiomeric catalyst (M)ꢀ1’.
oC for two hours (Fig. 1a and Fig. S4 in SI). A stacked plot of the
With the optimal reaction conditions in hands, the
dynamic circular dichroism (CD) traces of the photoisomerization enantiodivergent Steglich rearrangements of various Oꢀ
experiments of (P)ꢀ1 is shown in Fig. 1c. The observed positive carboxylazlactones, 6d-6k, with pseudoꢀenantiomeric catalysts (P)ꢀ1
exciton chirality at 221 nm clearly indicated the reversal of helical and (M)ꢀ1’ were further examined (Table 2). It was found that
chirality upon irradiation of (P)ꢀ1 at 290 nm.
rearrangements of 4ꢀethylꢀ and 4ꢀiꢀbutylꢀ1,3ꢀoxazolyl phenyl
Having established the complementary, photoꢀswitching profiles carbonates (R’ = Et and iꢀBu) catalyzed by either (P)ꢀ1 or (M)ꢀ1’
of pseudoꢀenantiomeric helicenes (P)ꢀ1 and (M)ꢀ1’, we investigated proceeded with excellent and complementary enantioselectivities
their individual performance as chiral organocatalysts in the Steglich (87ꢀ88% ee and 90ꢀ91% ee, respectively). Both products 7d,e were
rearrangement of Oꢀcarboxylazlactone (Table 1). Both (P)ꢀ1 and delivered in 80ꢀ85% yields (entries 1–4). Reaction of substrate 6f
(M)ꢀ1’ in the catalytic reaction are used in diastereomerically pure bearing 4ꢀiꢀpropylꢀsubstituent with (P)ꢀ1 or (M)ꢀ1’ gave the
form. In an initial study, Oꢀ1,1,1ꢀtrichloroꢀtertꢀbutoxycarbonyl (Cl3ꢀ corresponding products in 71 and 70% yield with complementary
tꢀBoc) derivative 6a was treated with 5 mol% of (P)ꢀ1 in CH2Cl2 at enantiomeric excess of 69 and 72% (entries 5,6). These poorer yields
ambient temperature, resulting in Cꢀcarboxylated product 7a in were due to partial hydrolysis of carbonate group in the resulting
modest yield of 57% with only 10% ee (entry 1). Replacement of the products, consistent with the works of Smith16a,c and Zhang.18
migrating Cl3ꢀtꢀBoc group with benzoxycarbonyl [BnOC(O)] and Substrates 6fꢀk bearing 4ꢀallyl (entries 7,8), 4ꢀ(2ꢀmethylthio)ethyl
phenoxycarbonyl [PhOC(O)] led to a significant improvement in the (entries 9,10), 4ꢀbenzyl (entries 11,12), 4ꢀ(4ꢀbenzyloxy)benzyl
enantioselectivities (41% and 63% ee; entries 2 and 3).25
(entries 13,14), and 4ꢀ(4ꢀphenoxycarbonyloxy)benzyl (entries 15,16)
groups were efficiently transformed into the corresponding products
7f-k in 81ꢀ86% yields with similarly excellent and complementary
enantioselectivities (87ꢀ91% ee and 91ꢀ94% ee, respectively).
Table Asymmetric Steglich rearrangement
1
of O-
carboxylazlactones catalyzed by (P)-1 or (M)-1’ in various solvents.
RO
5 mol%
(P)- or (M)-
Table
2 Asymmetric Steglich rearrangement of various O-
N
O
O
1
1'
N
O
*
carboxylazlactones catalyzed by (P)-1 or (M)-1’.
O
solvent, -40 o
C
OR
O
O
time
PhO
R'
O
6a-c
7a-c
R'
N
O
5 mol%
(P)-1 or (M)-1'
O
O
N
*
O
O
DME/TAA(1/1), -40 oC
24 h
OPh
O
entry
R
solvent
catalyst
time(h)
yield(%)b
ee (%)c
O
(config)d
O
6d-k
7d-k
O
1e
2
CMe2CCl3
CH2Cl2
CH2Cl2
CH2Cl2
(P)ꢀ1
(P)ꢀ1
(P)ꢀ1
48
6
57
85
90
10 (R)
41 (R)
63 (R)
(6a)
b
entr
y
R’
cataly
yield
(%)
ee (%)c
st
Bn (6b)
Ph (6c)
Ph (6c)
Ph (6c)
Ph (6c)
Ph (6c)
d
(config)
3
6
1
2
Et (6d)
Et (6d)
(P)ꢀ1
(M)ꢀ1’
(P)ꢀ1
85
83
84
80
71
70
86
82
84
81
85
82
83
81
85
82
88 (R)
91 (S)
87 (R)
90 (S)
69 (R)
72 (S)
88 (R)
91 (S)
87 (R)
91 (S)
90 (R)
94 (S)
91 (R)
93 (S)
87 (R)
90 (S)
4
5
6
7
toluene
Et2O
(P)ꢀ1
(P)ꢀ1
(P)ꢀ1
(P)ꢀ1
6
67
78
80
82
80 (R)
79 (R)
72 (R)
80 (R)
48
12
6
3
iꢀBu (6e)
iꢀBu (6e)
iꢀPr (6f)
iꢀPr (6f)
allyl (6g)
allyl (6g)
THF
4
(M)ꢀ1’
(P)ꢀ1
DME
5
8
Ph (6c)
DME/tAA
(1/1)
(P)ꢀ1
24
84
87 (R)
6
(M)ꢀ1’
(P)ꢀ1
7
9
Ph (6c)
DME/tAA
(1/1)
(M)ꢀ1’
24
81
91 (S)
8
(M)ꢀ1’
(P)ꢀ1
a The reactions were carried out in the presence of 5 mol% of (P)ꢀ1 at ꢀ40 oC under
nitrogen atmosphere. b Isolated yield. c The enantiomeric purity of 7 was determined by
using a chiral column (DAICEL Chiralcel ODꢀH) with hexane/propanꢀ2ꢀol as eluents. d
The absolute configuration of 7a-c were determined by comparison of the HPLC
retention time with those reported in reference 11a, 12, and 13. The reaction was
carried out at ambient temperature.
9
CH2CH2SMe (6h)
CH2CH2SMe (6h)
Bn (6i)
10
11
12
13
14
15
16
(M)ꢀ1’
(P)ꢀ1
e
Bn (6i)
(M)ꢀ1’
(P)ꢀ1
Further improvement in the enantioselectivity to around 80% ee
was achieved by changing the solvent to toluene, ether, or 1,2ꢀ
dimethoxyethane (entries 4–7), suggesting that ionic pair
intermediates may be solvated in polar solvents or stabilized by
aromatic solvents through cationꢀπ interaction.26 Final optimization
by using 1/1 mixture of 1,2ꢀdimethoxyethane (DME)/tꢀamyl alcohol
(tAA) led to the best results, giving (R)ꢀ7c in 84% yield with 87% ee
(entry 8).27 Conversely, the reaction of Oꢀcarboxylazlactone 6c
promoted by the pseudoꢀenantiomeric catalyst (M)ꢀ1’ gave
enantiomeric (S)ꢀ7c in 81% yield with 91% ee (entry 9). The switch
4ꢀBnOC6H4CH2(6j)
4ꢀBnOC6H4CH2(6j)
4ꢀPhO2COC6H4CH2(6k)
4ꢀPhO2COC6H4CH2(6k)
(M)ꢀ1’
(P)ꢀ1
(M)ꢀ1’
a
The reaction was carried out in the presence of 5 mol% of (P)ꢀ1 or (M)ꢀ1’ in 1,2ꢀ
dimethoxyethane/tertꢀamyl alcohol (v/v 1:1) at ꢀ40 oC under nitrogen atmosphere.
b
Isolated yields. c The enantiomeric purity of 7 was determined by using a chiral column
d
(DAICEL Chiralcel ODꢀH or ADꢀH) with hexane/propanꢀ2ꢀol as eluents The absolute
configuration of 7d and 7f-h were determined by comparison of the HPLC retention
time with those reported in reference 16a.
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Journal Name
MeO
OMe
In order to gain insight into the mechanism of Steglich
rearrangement catalyzed by (P)ꢀ1 or (M)ꢀ1’, the reversibility of Oꢀ to
Cꢀcarboxyl group transfer process was investigated through some
control experiments (Scheme 3). Initial crossover study was carried
out by treatment of a 50:50 mixture of Oꢀcarboxylazlactones 6c and
6l with 5 mol% of catalyst (P)ꢀ1 at ꢀ40 ℃ in DME/tAA (1/1) mixed
solvents. After 24 hours and reaction completion, a 22:27:23:28
mixture of four Cꢀcarboxylated products 7c, 7l, 7h, and 7i was
observed (see Fig. S11,12 in SI). Further control experiment was
performed by reaction of a mixture of Cꢀcarboxyl 7c and Oꢀcarboxyl
6l under the same reaction condition, giving Cꢀcarboxyl 7c and 7l,
exclusively (see Fig. S13 in SI). These results indicated that Cꢀ
carboxylated products are configurationally stable under reaction
conditions and that rapid crossover only occurs in Oꢀcarboxylation
stage, which is consistent with those reported by Fu using planar
chiral DAMPs11a and by Smith using chiral isothioureas or chiral
NHCs.16b,c Moreover, the complete crossover caused by rapid
transcarboxylation between two different Oꢀcarboxyl azalctones
indicated that ion pair intermediates are fully stabilized in the
DME/tAA (1/1) mixed solvents.
Cl
Cl
R
PhO
N
R
N
O
O
O
N
N
O
OPh
O
O
(P)-1
O
6
7
O
irreversible
C-carboxylation
with high
reversible
O-carboxylation
MeO
OMe
enantiocontrol
R
N
PhO
O
Cl
Cl
O
O
N
MeO
N
II
I
Scheme 4. Proposed mechanism for the Steglich rearrangement of O-
carboxylazlactone catalyzed by (P)-1.
To gain further insight into the origin of enantiocontrol in the
asymmetric catalytic process, molecular simulations of the transition
state assemblies in the ion pair were performed by DFT
calculations.28 The preferred transition state assembly, Aꢀsyn, with
Reꢀface attack leading to (R)ꢀ7 is shown in Fig. 2b.
Bn
Me
N
N
O
O
O
O
PMP
PMP
OPh
OBn
O
O
Presumably, the synclinal approach in Aꢀsyn assembly is more
favored than the corresponding antiperiplanar approach in Aꢀanti
assembly in view of the advantageous donorꢀacceptor type, πꢀπ
interaction in Aꢀsyn and the unfavorable steric repulsion between the
4ꢀmethoxyphenyl group and the C11ꢀmethoxymethyl group in Aꢀ
anti.
In transition state assembly Bꢀanti with antiperiplanar approach
and Siꢀface attack leading to (S)ꢀ7 (Fig. 2c), calculations show that
the barrier for the Siꢀface attack is 1.19 kcal mol−1 higher than that
for the Reꢀface attack (see Fig. S8ꢀS10 in SI). A greater overlap
between HOMO and LUMO is observed for the Reꢀface attack based
on the frontier molecular orbital analysis; therefore, the preference of
the Reꢀface attack is rationalized. In addition, the stereoelectronic
repulsions between the enolate oxygen lone pairs and the C11ꢀ
methoxymethyl group as well as between 4ꢀmethoxyphenyl and the
Nꢀmethyl groups in the bottom template also contribute to a higher
Gibbs free energy mentioned above.
6c
6l
5 mol% (P)-1
DME/TAA(1/1),
o
-40 C, 24 h
Me
Bn
Bn
N
CO Ph
CO Bn
2
2
N
N
N
O
O
O
O
O
O
O
O
PMP
PMP
OPh
OBn
PMP
PMP
O
O
6c
6l
7l
7c
Me
Bn
Bn
N
CO Bn
2
CO Ph
2
N
N
N
O
O
O
O
O
O
O
O
PMP
PMP
OBn
OPh
PMP
PMP
O
O
6b
6i
7i
7h
O-carboxyl crossover products
C-carboxyl crossover products
Scheme 3. Crossover experiments of O-carboxylazlactones 6c and 6l under
(a) A-syn and A-anti transition state assemblies
optimal reaction conditions.
Side view
Based on the control experiments, it was proposed that the
catalytic process may proceed through an initial and reversible
nucleophilic carboxyl substitution of the substrate carbonate moiety
by catalyst (P)ꢀ1, resulting in the formation of a stabilized ion pair
between enolate anionꢀI and pyridiniumꢀcation II (Scheme 4).11b The
carbonyl group in the phenoxycarbonyl moiety in II is anti with
respect to the 3ꢀchloro appendage in the top template, thus avoiding
stereoelectronic repulsion between the lone pairs of chlorine and the
carbonyl oxygen. Subsequently, an irreversible Cꢀcarboxylation of
enolate anionꢀI takes place with pyridiniumꢀcation II in high
enantiocontrol, giving the Cꢀcarboxylazlactone in R configuration.
MeO
Cl
LUMO
HOMO
Cl
O
MeO
O
N
N
N
OMe
Bn
-O
O
A-syn
4 | J. Name., 2012, 00, 1-3
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Bottom view
OMe
synclinal
1 For reviews of enantioselectivity switches using a single chiral
source, see: (a) G. Zanoni, F. Castronovo, M. Franzini, G. Vidari
and E. Giannini, Chem. Soc. Rev., 2003, 32, 115−129. (b) T.
steric
Ph
approach
O
11
O
O
11
O
Ph
O
-
10
face
Re
O
O
O
10
O
N
O
attack
Ph
N
Cl
N
Cl
Cl
Cl
O
O
O
N
Tanaka and M. Hayashi, Synthesis, 2008, 3361
−3376. (c) M.
O-
O
N
O
MeO
Ph
MeO
N
Bartók, Chem. Rev., 2010, 110, 1663−1705. (d) J. Escorihuela, M.
I. Burguete and S. V. Luis, Chem. Soc. Rev., 2013, 42,
5595−5617.
N
7
)-
(
R
A-syn
(favored)
antiperiplanar
approach
major
π π
-
interaction; supported by
molecular simulation
A-anti (less favored)
2 G. Storch and O. Trapp, Angew. Chem., Int. Ed., 2015, 54,
3580−3586.
(b) B-anti transition state assembly
3 Y. Sohtome, S. Tanaka, K. Takada, T. Yamaguchi and K.
Nagasawa, Angew. Chem., Int. Ed., 2010, 49, 9254−9257.
4 S. A. Moteki, J. Han, S. Arimitsu, M. Akakura, K. Nakayama and
K. Maruoka, Angew. Chem., Int. Ed., 2012, 51, 1187−1190.
5 J. Wang, J. Chen, C. W. Kee and C.ꢀH. Tan, Angew. Chem., Int.
Ed., 2012, 51, 2382−2386.
steric
O
11
10
O
O
PhO
O-
N
face
Si
Ph
O
N
O
attack
O
Cl
O
Cl
Ph
O
N
MeO
N
MeO
antiperiplanar
approach
7
( )-
S
minor
steric
6 Z. Wang, Z. Yang, D. Chen, X. Liu, L. Lin and X. Feng, Angew.
Chem., Int. Ed., 2011, 50, 4928ꢀ4932.
B-anti (disfavored)
7 (a) T. Yamamoto, T. Yamada, Y. Nagata and M. Suginome, J. Am.
Chem. Soc., 2010, 132, 7899−7901. (b) Y. Akai, T. Yamamoto, Y.
Nagata, T. Ohmura and M. Suginome, J. Am. Chem. Soc., 2012,
134, 11092−11095.
Fig. 2 Plausible transition state assemblies of Steglich rearrangement by
using (P)-1. (a) A-syn and A-anti transition state assemblies using GaussView
(side view) and ChemDraw (side and bottom views) presentations. (b) B-anti
transition state assembly using ChemDraw (bottom view) presentation.
8 S. Mortezaei, N. R. Catarineu and J. W. Canary, J. Am. Chem. Soc.,
2012, 134, 8054−8057.
9 (a) J. Wang and B. L. Feringa, Science, 2011, 331, 1429−1432. (b)
M. Vlatković, L. Bernard, E. Otten and B. L. Feringa, Chem.
Commun., 2014, 50, 7773−7775. (c) D. Zhao, T. M. Neubauer and
B. L. Feringa, Nature Commun., 2015, 6, 6652.
10 For reviews of photoswitchable catalysis, see: (a) B. M. Neilson
and C. W. Bielawski, ACS Catal., 2013, 3, 1874−1885. (b) R.
Göstl, A. Senf and S. Hecht, Chem. Soc. Rev., 2014, 43,
1982−1996. For representative example of photochemically
modulated enantioselectivity in asymmetric reaction, see : (c) D.
Sud, T. B. Norsten and N. R. Branda, Angew. Chem., Int. Ed.,
2005, 44, 2019−2021.
Conclusions
In summary, we have documented a pseudoꢀenantiomeric pair of
optically switchable helicene catalysts (10R,11R,P)ꢀ1 and
(10R,11R,M)ꢀ1’, which contain a 4ꢀNꢀmethylaminopyridine (MAP)
moiety. The helicene pair underwent complementary, photoꢀ
switching profiles at 290 nm (1/1’, <1/>99) and 340 nm (1/1’, 91/9)
and unidirectional thermoꢀrotation (1/1’, >99/<1), as evidenced by
UVꢀVis difference, CD, and HPLC analyses. They can efficiently
catalyze enantiodivergent Steglich rearrangements of Oꢀ to Cꢀ
o
carboxyazlactones at ꢀ40 C in DME/tAA mixed solvents, resulting
in the formation of either enantiomeric products of bioꢀmedicinal
importance29 in up to 91% (R) and 94% (S) ee, respectively. Control
experiments were performed to understand that the catalytic process
may proceed through a reversible Oꢀcarboxylation and a subsequent
irreversible Cꢀcarboxylation, Molecular simulations of the transition
state assemblies of the incipient ion pairs indicate that synclinal Reꢀ
face attack is favored in catalyst (P)ꢀ1 due to greater HOMOꢀLUMO
interactions with minimal stereoelectronic repulsions. To our
knowledge, this system provides the best complementary
enantioselectivities among several lightꢀ or heatꢀcontrolled
enantiodivergent catalytic reactions. Investigations toward
examining other substrate classes, as well as applications to other
organoꢀcatalytic systems are underway.
11 (a) J. C. Ruble and G. C. Fu, J. Am. Chem. Soc., 1998, 120,
11532−11533. (b) I. D. Hills and G. C. Fu, Angew. Chem., Int. Ed.,
2003, 42, 3921−3924.
12 H. V. Nguyen, D. C. D. Butler and C. J. Richards, Org. Lett.,
2006, 8, 769ꢀ772.
13 S. A. Shaw, P. Aleman and E. Vedejs, J. Am. Chem. Soc., 2003,
125, 13368−13369.
14 T. Poisson, S. Oudeyer and V. Levacher, Tetrahedron Lett., 2012,
53, 3284ꢀ3287
15 H. Mandai, T Fujiwara, K. Noda, K. Fujii, K. Mitsudo, T.
Korenaga and S. Suga, Org. Lett. 2015, 17, 4436ꢀ4439.
16 (a) C. Joannesse, C. P. Johnston, C. Concellon, C. Simal, D. Philp
and A. D. Smith, Angew. Chem., Int. Ed., 2009, 48, 8914−8918. (b)
C. D. Campbell, C. Concellon and A. D. Smith, Tetrahedron:
Asymmetry, 2011, 22, 797ꢀ811. (c) C. Joannesse, C. P. Johnston, L.
C. Morrill, P. A. Woods, M. Kieffer, T. A. Nigst, H. Mayr, T.
Lebl, D. Philp, R. A. Bragg and A. D. Smith, Chem.−Eur. J.,
2012, 18, 2398ꢀ2408.
Acknowledgements
Financial support from the Ministry of Science of Technology of
Taiwan (MOST 104ꢀ2113ꢀMꢀ007 ꢀ002 ꢀMY3 and 104ꢀ2113ꢀMꢀ007ꢀ
014) was greatly acknowledged.
17 D. Uraguchi, K. Koshimoto, S. Miyake and T. Ooi, Angew.
Chem., Int. Ed., 2010, 49, 5567−5569.
Notes and references
18 Z. Zhang, F. Xie, J. Jia and W. Zhang, J. Am. Chem. Soc., 2010,
132, 15939–15941.
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19 (a) C.ꢀT. Chen and Y.ꢀC. Chou, J. Am. Chem. Soc., 2000, 122,
7662−7672. (b) W.ꢀC. Chen, Y.ꢀW. Lee and C.ꢀT. Chen, Org.
Lett., 2010, 12, 1472−1475. (c) W.ꢀC. Chen, P.ꢀC. Lin, C.ꢀH.
Chen and C.ꢀT. Chen, Chem.−Eur. J., 2010, 16, 12822−12830. (d)
C.ꢀT. Chen, C.ꢀH. Chen and T.ꢀG. Ong, J. Am. Chem. Soc., 2013,
135, 5294−5297.
20 For reviews of chiral dialkylaminopyridine catalysts in
asymmetric synthesis, see: (a) R. P. Wurz, Chem. Rev., 2007, 107,
5570ꢀ5595. (b) T. Furuta and T. Kawabata, in Science of
Synthesis: Asymmetric Organocatalysis; B. List and K. Maruoka,
ed. Thieme, 2012; pp. 497ꢀ546.
21 M. R. Heinrich, H. S. Klisa, H. Mayr, W. Steglich and H. Zipse,
Angew. Chem., Int. Ed. 2003, 42, 4826−4828.
22 The negative exciton chirality is attributed to the electric
transition dipole moment change from the bottom template to the
top right.
23 The diastereomeric excess (de) of the pss at a given irradiation
wavelength is given by [de]pss = (PꢀM’)/(P+M’) = [(εM’ ΦM’ →P ꢀ εP
ΦP →M’ )/ [(εM’ ΦM’ →P + εP ΦP →M’ )].
24 (M)ꢀ1’ is unavailable by chemical synthesis but subsequently
obtained by photoisomerization of (P)ꢀ1 at 290 nm in CH2Cl2 for
1 hour.
25 The ee values of the resulting products were improved by about
10%, when the reaction temperature was lowered from 0 to ꢀ40 ℃.
26 The calculated energy differences between the transition states in
various solvents are less than 0.5 kcal mol−1; therefore, the similar
enantioselectivities in toluene, Et2O, and DME are rationalized.
27 The control experiments in this work indicated the formation of a
solventꢀseparated ion pair in the DME/tAA (1/1) mixed solvents,
suggesting that the enolate anion in the ionꢀpair intermediate may
be further stabilized by the additional tAA through partial
hydrogenꢀbonding interaction.
28 Four transition states derived from (P)ꢀ1 or (M)ꢀ1’ along with two
possibilities of facial selectivity of enolate anionꢀI are shown in
Gaussview presentation (Fig. S5) as well as in Chem 3D and
Chem Draw presentations (see Fig. S6,7 in SI).
29 For a review of significance of α,αꢀdisubstituted azlactones,
see: (a) R. A. Mosey, J. S. Fisk and J. J. Tepe, Tetrahedron:
Asymmetry, 2008, 19, 2755ꢀ2762. For a representative
example of bioꢀmedicinal importance of α,αꢀdisubstituted
azlactones, see : (b) T. Zhou, R. C. Hider, P. Jenner, B.
Campbell, C. J. Hobbs, S. Rose, M. Jairaj, K. A. Tayayraniꢀ
Binazir and A. Syme. Bioorg. Med. Chem. Lett., 2013, 23
,
5279-5282.
6 | J. Name., 2012, 00, 1-3
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