J. Am. Chem. Soc.

2000, 122, 11525-11526 11525

Enantioselective Intermolecular Scheme 1

[2 + 2]-Photocycloaddition Reactions of Alkenes and
a 2-Quinolone in Solution

Thorsten Bach*,† and Hermann Bergmann‡

Lehrstuhl für Organische Chemie I

Technische UniVersität München
D-85747 Garching, Germany
Fachbereich Chemie,
Philipps-UniVersität Marburg
D-35032 Marburg, Germany

ReceiVed July 20, 2000

ReVised Manuscript ReceiVed September 26, 2000
In recent years, there has been tremendous progress in the
enantioselective synthesis of strained compounds by intramo-
lecular photochemical reactions.1 Chiral organic2 and inorganic3 Scheme 2
complexing agents have been employed successfully in solid-
state photochemistry. Homochiral crystals of prochiral substrates
have been obtained by the “ionic chiral auxiliary” approach4 or
by other methods5 and yielded enantiomerically enriched products
upon irradiation. In the liquid phase, many efforts have centered
on the use of circular polarized light to induce an effective
differentiation of enantiotopic faces and enantiomeric excesses
(ee’s) up to 64% have been recorded.6 Enantioselective photo-
cycloaddition reactions in solution have been achieved using chiral
host molecules which bind the substrate by hydrogen bonding.7
An advantage of the latter approach as compared to the methods based receptors which we have recently prepared in our labora-
employed in the solid state is the fact that it should also be tory.7,12 The endo- and exo-isomers 2 and 3 and their enantiomers
applicable to intermolecular photochemical reactions of two ent-2 and ent-3 are obtained as products, the exo/endo ratio being
different reaction partners. Contrary to the classical auxiliary- dependent on the substituent R (vide infra).
based methodology which has been elegantly applied in photo- Binding to a chiral host should facilitate a differentiation of
cycloaddition chemistry8,9 the use of a noncovalently bound the enantiotopic faces of compound 1. For the current set of
complexing agent avoids the cleavage of the chiral source.10 We experiments we have employed the chiral amide 4 and its
would now like to report on our preliminary results with regard enantiomer ent-4 (Scheme 2). As depicted in Scheme 2 the
to enantioselective (81-98% ee) intermolecular [2 + 2]-photo- quinolone 1 was expected to coordinate to the lactam 4 with its
cycloadditions in solution. NH-group being the hydrogen donor and with the carbonyl group
The quinolone 1 is known to undergo a [2 + 2]-photocyclo- being the hydrogen acceptor. In previous studies it was shown
addition with different alkene substrates (Scheme 1).11 Its lactam that the association contants of six-membered lactams related to
functionality should be well suited for binding to the lactam- 1 and host molecules related to 4 are high and that the
†
Technische Universität München. self-association of the host is low.13 It was consequently expected
‡
Philipps-Universität Marburg. that the quinolone 1 undergoes a selective photocycloaddition,
(1) Reviews: (a) Everitt, S. R. L.; Inoue, Y. In Molecular and Supramo- provided that it binds to the host and provided that the
lecular Photochemistry: Organic Molecular Photochemistry; Ramamurthy,
V., Schanze, K. S., Eds.; Dekker: New York, 1999; Vol. 3, p 71. (b) Inoue, intermolecular reaction occurs at the bound substrate.
Y. Chem. ReV. 1992, 92, 741. (c) Rau, H. Chem. ReV. 1983, 83, 535. The studies were conducted with different alkenes (Scheme 1,
(2) Reviews: (a) Ito, Y. Synthesis 1998, 1. (b) Toda, F. Acc. Chem. Res. Table 1). Only selected experimental data are provided in Table
1995, 28, 480.
(3) Review: Joy, A.; Ramamurthy, V. Chem. Eur. J. 2000, 6, 1287-1293. 1, additional data can be found in the Supporting Information.
(4) Review: Gamlin, J. N.; Jones, R.; Leibovitch, M.; Patrick, B.; Scheffer, The best results were obtained at low-temperature employing an
J. R.; Trotter, J. Acc. Chem. Res. 1996, 29, 203. excess of the host (entries 1, 2, and 3). Either enantiomer of the
(5) Review: Sakamoto, M. Chem. Eur. J. 1997, 3, 684.
(6) Inoue, Y.; Wada, T.; Asaoka, S.; Sato, H.; Pete, J.-P. J. Chem. Soc., host 4 or ent-4 was used in these experiments. As expected the
Chem. Commun. 2000, 251 and references therein. product with opposite configuration was obtained upon exchang-
(7) Bach, T.; Bergmann, H.; Harms, K. Angew. Chem., Int. Ed. 2000, 39, ing the host (entries 4 and 5). In the case of vinyl acetate (R )
2302.
(8) For seminal contributions, see: (a) Tolbert, L. M.; Ali, M. B. J. Am. OAc) both cyclobutane isomers ent-2c (endo) and ent-3c (exo)
Chem. Soc. 1982, 104, 1742. (b) Koch, H.; Runsink, J.; Scharf, H.-D. were isolated. The optical purity of the two diastereoisomers was
Tetrahedron Lett. 1983, 24, 3217. (c) Meyers, A. I.; Fleming, S. A. J. Am. similar (entry 6). In general, the simple diastereoselectivities
Chem. Soc. 1986, 108, 306. (d) Demuth, M.; Palomer, A.; Sluma, H.-D.; Dey,
A. K.; Krüger, C.; Tsay, Y.-H. Angew. Chem. 1986, 98, 1093; Angew. Chem., (endo/exo ratios) determined in the presence of the chiral host
Int. Ed. Engl. 1986, 25, 1117. did not significantly differ from the diastereoselectivities obtained
(9) Reviews: (a) Fleming, S. A.; Bradford, C. L.; Gao, J. J. In Molecular
and Supramolecular Photochemistry: Organic Photochemistry; Ramamurthy, (11) (a) Kaneko, C.; Naito, T.; Chem. Pharm. Bull. 1979, 27, 2254. (b)
V., Schanze, K. S., Eds.; Dekker: New York, 1997; Vol. 1, p 187. (b) Bach, Kaneko, C.; Naito, T. Heterocycles 1982, 19, 2183. (c) Kaneko, C.; Suzuki,
T. Synthesis 1998, 683. (c) Mattay, J.; Conrads, R.; Hoffmann, R. In Methoden T.; Sato, M.; Naito, T. Chem. Pharm. Bull. 1987, 35, 112-123.
der Organischen Chemie (Houben-Weyl), 4th ed.; Helmchen, G., Hoffmann, (12) For the synthesis of related compounds and their use as chiral
R. W., Mulzer, J., Schaumann, E., Eds.; Thieme: Stuttgart, 1995; Vol. E 21c, auxiliaries, see: Stack, J. G.; Curran, D. P.; Geib, S. V.; Rebek, Jr., J.; Ballester,
p 3085. P. J. Am. Chem. Soc. 1992, 114, 7007.
(10) For the use of chiral proton sources in enantioselective photodecon- (13) Bach, T.; Bergmann, H.; Harms, K. J. Am. Chem. Soc. 1999, 121,
jugation reactions, see: Pete, J.-P. AdV. Photochem. 1996, 21, 135. 10650.

10.1021/ja0026760 CCC: $19.00 © 2000 American Chemical Society

Published on Web 11/03/2000
11526 J. Am. Chem. Soc., Vol. 122, No. 46, 2000 Communications to the Editor

Table 1. Enantioselective Photocycloaddition of the 2-Quinolone 1 in the Presence of the Chiral Host Compounds 4 and ent-4
entry Ra temp [°C] time [h]b host equiv drc (3/2) yield [%]d product ee [%]e
1 CH2CH2CH2OH 30 2 4 1.4 >95/5 75 3a 30
2 CH2CH2CH2OH -20 10 4 1.3 >95/5 74 3a 52
3 CH2CH2CH2OH -60 10 4 2.4 >95/5 80 3a 81
4 CH2OAc -60 10 4 2.4 >95/5 80 3b 92
5 CH2OAc -60 10 ent-4 2.4 >95/5 81 ent-3b 91
6 OAc -60 10 ent-4 2.4 63/27 89 ent-3c 93
ent-2c 98
7 Ph -60 10 4 2.4 <5/95 10 f 2d 83
8 COOCH3 -60 10 4 2.4 90/10 84 3e 82 g
a The reaction was conducted in an immersion apparatus (Duran filter; light source: Original Hanau TQ 150). The quinolone concentration was

2 × 10-3 M in toluene as the solvent. The alkene was used in excess (20 equiv). After complete conversion the solvent and the excess alkene was
removed in vacuo and the residue was purified by flash chromatography (gradient: tert-butyl methyl ether/pentane). b Time after which the conversion
was complete (except for entry 7). c The diastereomeric ratio of cyclobutanes in the crude product was determined by integration of appropriate 1H
NMR signals. d Yield of isolated product. e The enantiomeric excess was determined by chiral HPLC (Chiracel OD; eluent: hexane/i-propanol )
92/8). f The reaction remained incomplete even upon prolongued irradiation. 65% of the quinolone was recovered. g The enantiomeric excess was
determined by chiral HPLC after reduction (LiBH4 in THF/EtOH) to the corresponding amino alcohol.

in its absence (see Supporting Information). The enantiomeric Scheme 3

excesses achieved at -60 °C were high, and they demonstrate
that the enantioface differentiation provided by the bulky tetra-
hydronaphthalene backbone is very efficient. The host was
recovered after separation by flash chromatography (80-95%
recovery).
The assignment of the absolute configuration was based on
our previous results obtained in the intramolecular reaction of
2-quinolones.7 A Re face attack at the carbon atom C-3 occurs if
host 4 is employed. As depicted in Scheme 2, Re attack at this
Acknowledgment. This paper is dedicated to Professor Horst Kunz
position leads to the formation of products 2 (endo) or 3 (exo).
on the occasion of his 60th birthday. This work was generously supported
The relative configuration was assigned based on NOESY data by the Deutsche Forschungsgemeinschaft and by the Fonds der Chemis-
and on previous work.11 The enantioselective photochemical chen Industrie.
reaction was extended to symmetrical 1,1-disubstituted alkenes.
As an example the conversion of 2-ethyl-1-butene (5) to the
cyclobutane 6 is presented in Scheme 3. Supporting Information Available: Comprehensive table of the
In summary, the host compound 4 and its enantiomer ent-4 irradiation study including the irradiation results in the absence of the
host; NMR data and spectra (1H, 13C) of 2c, 2d, 3a, 3b, 3c, 3e, and 6;
have proved to be reliable chiral complexing agents for enantio-
further analytical data and HPLC analyses of 3a, 3b (entry 4), 2c and 3c
selective intermolecular [2 + 2]-photocycloaddition reactions of
(entry 6), 2d (entry 7), and 6 (Scheme 3) (PDF). This material is available
2-quinolones. Further studies are directed toward additional free of charge via the Internet at http://pubs.acs.org.
applications of these hosts in inter- and intramolecular photo-
chemical reactions. These results will be reported in due course. JA0026760