Reactive spin state dependent enantiospecific photocyclization of axially chiral α-substituted acrylanilides

Article abstract of DOI:10.1039/c0cc04416d

The enantiomeric ratio (e.r.) in the 3,4-dihydroquinolin-2-one photoproduct during 6π-photocyclization of α-substituted axially chiral ortho-tert-butyl-acrylanilides depends on the nature of the reactive spin state (singlet or triplet), where the singlet-

Full text of DOI:10.1039/c0cc04416d

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COMMUNICATION
Reactive spin state dependent enantiospecific photocyclization of axially
chiral a-substituted acrylanilidesw
Anoklase Jean-Luc Ayitou and J. Sivaguru*
Received 14th October 2010, Accepted 25th November 2010
DOI: 10.1039/c0cc04416d
The enantiomeric ratio (e.r.) in the 3,4-dihydroquinolin-2-one
photoproduct during 6p-photocyclization of a-substituted
axially chiral ortho-tert-butyl-acrylanilides depends on the
nature of the reactive spin state (singlet or triplet), where
the singlet-spin state reactivity gives a racemic mixture and
the triplet reactivity gives an e.r. value >95 : 5.
chiral acrylanilides, we observed efficient photocyclization
upon triplet-sensitized irradiations. To examine the role of
the reactive spin-state we investigated the enantiospecific
6p-photocyclization of 1a–b (Scheme 1) under direct and
triplet-sensitized irradiations to divulge the critical role
of the reactive spin-state (S1 or T1) in determining the
enantiomeric ratio (er values) in 2.
Triplet sensitized irradiation of 1a–b in acetone (serving as
both solvent and sensitizer) gave photoproduct 2 with er
values >95 : 5 at ambient conditions (Table 1). Optical
antipodes of 1 gave the opposite enantiomers in 2 indicating
that the system was well behaved. For example, triplet sensitized
irradiation of (ꢀ)-1b and (+)-1b in acetone gave er values
>95 : 5 of 2b and ent-2b respectively (Scheme 1; HPLC
insert). Direct irradiation of (ꢀ)-1b or (+)-1b under identical
The role of the excited spin state (singlet Sn or triplet Tn)
determining the course of light initiated reactions is well
documented in the literature.1–8 There are a number of elegant
examples of reactions from S1 or T1 leading to different
reactivities and/or photoproducts.4–6,9 Various groups in the
last four decades have investigated10–13 the role of reactive
spin states in regioselective and diastereoselective photo-
chemical transformations in solution14,15 and in organized
assemblies.16,17 An intriguing aspect in this regard involves
the spin dependent selectivity in photochemical reactions
leading to the same photoproduct with varying enantio-
selectivities.10,11 One of the classical reports involves g-hydrogen
abstraction in which the singlet spin-state reactivity gives very
high enantiomeric excess and triplet reactivity leads to a
racemic mixture of photoproducts.10,11 Herein we report a
reactive spin state (S1 or T1) dependent photocyclization of
axially chiral a-substituted acrylanilides 1a–b to 3,4-dihydro-
2-quinolin-2-one photoproduct 2, where the singlet reactivity
(via direct irradiation) leads to a racemic mixture, while the
corresponding triplet reactivity (via triplet sensitization)
leads to enantiomeric ratios (er values) >95 : 5 in the
Table 1 Enantiospecific 6p-photocyclization of 1 under direct and
triplet sensitized irradiationsa–e
Entry Cmpdb Solvent
Sens.c
Mode
T/1C er 2e
1
2
3
4
(+)1a
Acetone Acetone Triplet 20
Acetone Acetone Triplet 27
96 : 04 (A)
90 : 10 (A)
Racemic
TFE
MeOH
—
—
Singlet 27
Singlet 27
Racemic
3,4-dihydro-2-quinolin-2-one photoproduct
2 at ambient
5
6
7
8
(ꢀ)1a
Acetone Acetone Triplet 20
Acetone Acetone Triplet 27
97 : 03 (B)
90 : 10 (B)
Racemic
conditions.
TFE
MeOH
—
—
Singlet 27
Singlet 27
We recently reported18,19 that axially chiral chromophores
can be employed to achieve a very high enantiomeric excess in
the photoproduct(s) in solution. Constraints that make the
reactants axially chiral are based on the well-established
concepts of rotamer control via restricted bond rotation that
have been successfully employed for various chemical
transformations.20–23 During our investigation of axially
Racemic
9
(+)1b
(ꢀ)1b
Acetone Acetone Triplet 20
Acetone Acetone Triplet 27
97 : 03 (A)
90 : 10 (A)
Racemic
96 : 04 (B)
90 : 10 (B)
Racemic
10
11
12
13
14
TFE
—
Singlet 27
Acetone Acetone Triplet 20
Acetone Acetone Triplet 27
TFE
—
Singlet 27
a
Reported values are an average of a minimum of 3 runs with ꢁ5%
b
error. TFE: trifluoroethanol. (+) and (ꢀ) represent the signs of their
c
CD signals at 285 nm in methylcyclohexane (MCH). Sensitizer’s
Department of Chemistry and Biochemistry,
triplet energies (ET) for acetone: B79 kcal molꢀ1
.
Conversion
d
North Dakota State University, Fargo, ND 58108-6050, USA.
E-mail: sivaguru.jayaraman@ndsu.edu; Fax: +1 701-231-8831;
Tel: +1 701-231-8923
w Electronic supplementary information (ESI) available: Experimental
procedures for photoreactions, synthesis, characterization and
analysis conditions. See DOI: 10.1039/c0cc04416d
1
calculated by H NMR using a,a0-dichloro-p-xylene as internal
e
standard (refer to ESI w). A and B refers to the first and second
peak that elutes out on the HPLC chiral stationary phase separation
for a given pair of enantiomers.
c
2568 Chem. Commun., 2011, 47, 2568–2570
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Scheme 1 Photocyclization of axially chiral a-substituted acrylanilides under direct (singlet) and sensitized (triplet) irradiations.
conditions in trifluoroethanol (TFE) gave a racemic mixture
of 2. There was a minimal decrease in the er values from
>95 : 5 to 90 : 10 upon increasing the temperature from 20 1C
to 27 1C due to the slow racemization (slow N–C(aryl) bond
rotation in the reactant 1a–b at elevated temperatures). Both
1a–b showed fluorescence (Fig. 1A) at room temperature in
methylcyclohexane (MCH). The emission maxima shifts
bathochromically upon changing the solvent from non-polar
MCH to polar solvents like ethanol or acetonitrile (ESI w),
similar to the fluorescence emission behaviour of other
methacrylanilides reported in the literature.24 Additionally,
for 1a–b we observed phosphorescence (Fig. 1A) at 77 K in
MCH glass with a triplet energy (ET) of B77.3 kcal molꢀ1 and
a lifetime (tp) of B1.58 s (Fig. 1B) (ESI w). Based on the
emission studies, it is clear that the lowest excited singlet and
triplet state has a pp* configuration in 1a–b.
Based on the established paradigm25 for photochemical
reactions viz. photocyclization, a zwitterionic intermediate is
expected for the photocyclization from the pp* singlet excited-
state S1(pp*) and a diradicaloid intermediate is likely from the
corresponding pp* triplet excited-state T1(pp*).25 This
prompted Ogata and co-workers24,26 to propose a zwitterionic
intermediate originating from the singlet pp* (S1 pp*)
excited-state for the 6p-photocyclization of achiral acrylanilide
(N–H substituted derivative without the ortho-tert-butyl group
on the phenyl ring). In the case of 1a–b, we believe that the
restricted N–C(aryl) bond rotation not only imparts axial
chirality (molecular chirality) to the system but also enables
us to access the triplet state (as we observe phosphorescence)
at 77 K in MCH glass. While in the case of an achiral N–H
acrylanilide (viz., ortho-tert-butyl N–H acrylanilide 1d) we
failed to observe any phosphorescence at 77 K, both achiral
and axially chiral N-methyl derivatives 1a–c (axially chiral
1a–b and achiral 1c) gave observable phosphorescence at 77 K
Fig. 1 (A) Fluorescence (green at 298 K) and phosphorescence
(red, blue at 77 K) of 1a in methylcyclohexane (MCH). (B) Phos-
phorescence decay kinetics at 77 K in MCH glass. (C) Role of
N-methyl and N–H substitution.
in MCH glass (ESI w). Thus the presence of the N–Me
substituent is crucial to access the triplet-excited manifold.
We believe that the enolization of the N–H acrylanilides (as in
1d; Fig. 1C) to the enol form enables it to cyclize only from the
singlet-excited state, as it is oriented optimally for 6p-photo-
cyclization. On the other hand, in the case of the N-methyl
derivatives (as in 1a–c; Fig. 1C), the nitrogen lone pair is part
of the 6p-backbone leading to photoreactivity from the pp*
c
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Chem. Commun., 2011, 47, 2568–2570 2569

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excited state. Based on the phosphorescence, the triplet pp*
state of 1a–b lies at B77 kcal molꢀ1. Hence triplet energy
Notes and references
1 N. J. Turro, Chem. Eng. News, 1967, 45, 84.
transfer from acetone (ET E 79 kcal molꢀ1 27
is quite likely.
)
2 G. Quinkert, Angew. Chem., Int. Ed., 1975, 14, 790.
3 G. S. Hammond, J. Saltiel, A. A. Lamola, N. J. Turro,
J. S. Bradshaw, D. O. Cowan, R. C. Counsell, V. Vogt and
C. Dalton, J. Am. Chem. Soc., 1964, 86, 3197.
4 S. S. Hixson, P. S. Mariano and H. E. Zimmerman, Chem. Rev.,
1973, 73, 531.
5 D. A. Plattner, Angew. Chem., Int. Ed., 1999, 38, 82.
6 H. E. Zimmerman and G. A. Epling, J. Am. Chem. Soc., 1970, 92,
1411.
7 H. E. Zimmerman and D. I. Schuster, J. Am. Chem. Soc., 1962, 84,
4527.
8 H. E. Zimmerman and D. J. Schuster, J. Am. Chem. Soc., 1961, 83,
4486.
9 W. Adam, G. Fragale, D. Klapstein, W. M. Nau and J. Wirz,
J. Am. Chem. Soc., 1995, 117, 12578.
10 B. Giese, P. Wettstein, C. Stahelin, F. Barbosa, M. Neuburger,
¨
M. Zehnder and P. Wessig, Angew. Chem., Int. Ed., 1999, 38, 2586.
11 A. G. Griesbeck, W. Kramer and J. Lex, Angew. Chem., Int. Ed.,
2001, 40, 577.
The involvement of the triplet spin state viz., T1(pp*) in the
reaction path way was ascertained by carrying out the reaction
under O2 saturated conditions that resulted in o5%
conversion.28 Thus 6p-photocyclization of 1a–b could possibly
occur from either the singlet (S1) or the triplet (T1) spin-state
depending on the reaction conditions.29
Based on our mechanistic study28 we showed that the
6p-photocyclization upon direct irradiation in the case of
ortho-tert-butyl substituted axially chiral acrylanilides occurs
at the ortho carbon via the zwitterionic intermediate ‘‘int-ZW’’
(Scheme 1; top) followed by a non-stereo-specific hydrogen
migration with the eventual loss of the ortho-tert-butyl
substituent. As the photocyclization occurs from the S1(pp*)
excited state upon direct irradiation in the case of 1a–b, the
formation of
a zwitterionic intermediate (int-ZW) is
12 M. Sakamoto, H. Kawanishi, T. Mino and T. Fujita, Chem.
Commun., 2008, 2132.
expected.24,26,30,31 Similarly, triplet sensitized irradiation of
13 J. Sivaguru, T. Shichi and V. Ramamurthy, Org. Lett., 2002, 4, 4221.
14 Y. Inoue, in Chiral Photochemistry, ed. Y. Inoue and
V. Ramamurthy, Marcel Dekker, New York, 2004, p. 129.
15 H. Rau, Chem. Rev., 1983, 83, 535.
16 V. Ramamurthy, in Photochemistry in Organized and Constrained
Media, ed. V. Ramamurthy, Wiley-VCH, New York, 1991, p. 429.
17 T. Mori, Y. Inoue and R. G. Weiss, Org. Lett., 2003, 5, 4661.
18 A. J.-L. Ayitou, J. Jesuraj, N. Barooah, A. Ugrinov and
J. Sivaguru, J. Am. Chem. Soc., 2009, 131, 11314.
19 A. J.-L. Ayitou and J. Sivaguru, J. Am. Chem. Soc., 2009, 131,
5036.
1a–b leads to photocyclization from the T1(pp*) excited state
resulting in
a diradical (triplet diradical) intermediate
‘‘int-DR’’ (Scheme 1; bottom). This triplet diradical
‘‘int-DR’’ subsequently abstracts a hydrogen atom from the
ortho-tert-butyl substituent leading to 3,4-dihydroquinolin-
2-one photoproduct 2. The high enantiomeric ratio (Table 1)
in the photoproduct 2 under sensitized irradiation points out a
stereospecific hydrogen abstraction via a cyclic six membered
transition (Scheme 1; bottom) state from the triplet diradical
intermediate (int-DR). Thus the excited spin state S1(pp*) or
T1 (pp*) not only leads to the same photoproduct via two
different reactive intermediates and/or transition states, but
also determines the er values in the photoproduct.
20 D. P. Curran, H. Qi, S. J. Geib and N. C. DeMello, J. Am. Chem.
Soc., 1994, 116, 3131.
21 D. P. Curran, G. R. Hale, S. J. Geib, A. Balog, Q. B. l. Cass,
A. L. G. Degani, M. Z. Hernandes and L. C. G. Freitas,
Tetrahedron: Asymmetry, 1997, 8, 3955.
22 J. Clayden, Chem. Commun., 2004, 127.
23 A. Honda, K. M. Waltz, P. J. Carroll and P. J. Walsh, Chirality,
2003, 15, 615.
Axially chiral chromophores in conjunction with their
corresponding achiral counterparts, offer rich and divergent
photoreactivity that helps us to better understand mechanisms
of light induced stereospecific transformations. Our current
investigation with a-substituted acrylanilides has highlighted
the critical role of the reactive spin state in determining the
enantiomeric excess through two different photochemical
pathways leading to the same photoproduct.
24 Y. Ogata, K. Takagi and I. Ishino, J. Org. Chem., 1971, 36, 3975.
25 N. J. Turro, Modern Molecular Photochemistry, University Science
Books, New York, 1991, pp. 228–230 and 264–266.
26 I. Ninomiya, S. Yamauchi, T. Kiguschi, A. Shinobara and
T. Naito, J. Chem. Soc., Perkin Trans. 1, 1974, 1747.
27 S. L. Murov, I. Carmichael and G. L. Hug, Handbook of
Photochemistry, Marcel Dekker, New York, 1993, pp. 54–98.
28 A. J.-L. Ayitou, A. Ugrinov and J. Sivaguru, Photochem.
Photobiol. Sci., 2009, 8, 751.
The authors thank the financial support of NSF (CAREER:
CHE-0748525). The authors thank the NSF for a Graduate
Student Fellowship and UNCF/MERCK science initiative
research grant to AJA. The authors thank Dr Steffen
Jockusch, Columbia University for insightful discussions on
the photophysical aspects detailed in the manuscript.
29 R. Lapouyade, C. Manigand and A. Nourmamod, Can. J. Chem.,
1985, 63, 2192.
30 O. L. Chapman and W. R. Adams, J. Am. Chem. Soc., 1968, 90,
2333.
31 T. Bach, B. Grosch, T. Strassner and E. Herdtweck, J. Org. Chem.,
2003, 68, 1107.
c
2570 Chem. Commun., 2011, 47, 2568–2570
This journal is The Royal Society of Chemistry 2011