2452
J. Am. Chem. Soc. 2001, 123, 2452-2453
Scheme 1
Unusual Temperature-Dependent Diastereoselectivity
in the [2+2] Photocycloaddition (Paterno`-Bu1chi
Reaction) of Benzophenone to cis- and
trans-Cyclooctene through Conformational Control
Waldemar Adam,* Veit R. Stegmann, and Stephan Weinko¨tz
Institute of Organic Chemistry, UniVersity of Wu¨rzburg
Am Hubland, D-97074 Wu¨rzburg, Germany
Table 1. Temperature Dependence on the Diastereoselectivity of
the Oxetane Formation with cis-Cyclooctene (cis-1)
ReceiVed October 31, 2000
cis-1
entry temp (°C) time (min) convna (%) mba,b (%) dr 2a,c (cis:trans)d
The stereoselectivity in the [2+2] photocycloaddition of
carbonyl compounds to alkenes (Paterno`-Bu¨chi reaction) is still
an issue of current interest and intensive activity.1 In the past,
the Paterno`-Bu¨chi reaction of aldehydes and ketones with cis-
cyclooctene (cis-1) has been extensively investigated;2 however,
the corresponding trans isomer (trans-1) has not been employed.
Since in numerous cycloadditions with trans-cyclooctene3 the
trans configuration in the cycloadduct is preserved, it was of
mechanistic import to assess whether this also applies to the triplet
diradical intermediate of the Paterno`-Bu¨chi reaction between
trans-cyclooctene and benzophenone. We report herein an
unprecedented temperature-dependent diastereoselectivity in the
[2+2] photocycloaddition of benzophenone with the cyclooctenes
cis- and trans-1 (Scheme 1). Although the temperature dependence
of the stereoselectivity in [2+2] photocycloadditions is well
established4 and the results for the Paterno`-Bu¨chi reaction form,
in fact, the basis of the isoinVersion principle,5 we herewith
document the unusual case that the lower-energy substrate
diastereomer (cis-1 cyclooctene) affords with increasing temper-
ature the higher-energy product diastereomer (trans-2 oxetane);
the interplay of enthalpy and entropy are held responsible for
this. The Paterno`-Bu¨chi reactions were performed in d8-toluene,
the product composition was assessed by 1H NMR spectroscopy
(600 MHz) directly on the crude product mixture. This procedure
allowed the determination of the cis/trans ratio of the cycloadducts
over a large temperature range (-95 to +110 °C).
1
2
3
4
5
6
7
8
9
-95
-80
-60
-40
-20
0
20
40
60
80
10
10
10
10
10
10
10
10
10
5
11
19
28
30
33
37
45
46
48
28
33
32
98
99
97
97
94
92
87
84
81
89
86
85
98:02
88:12
76:24
59:41
45:55
36:64
27:73
25:75
23:77
21:79
20:80
20:80
10
11
12
100
110
5
5
1
a Determined by H NMR spectroscopy (600 MHz) directly on the
crude product mixture; error limits (5% of the given values; sum of
the aromatic signals were taken as internal standard (see Supporting
Information). b Mass balance. c Diastereomeric ratio (dr) of the cis- and
trans-2 oxetanes. d Benzpinacol (2-28%) was also formed.
Table 2. Temperature Dependence on the Diastereoselectivity of
the Oxetane Formation with trans-Cyclooctene (trans-1)
trans-1
temp time convna mba,b
dr 2a,c,d
product
entry (°C) (min)
(%)
(%) (cis:trans) ratioa cis-1:2′
1
2
3
4
5
6
7
8
9
-80
-60
-40
-20
0
20
40
60
80
100
110
10
10
10
10
10
10
5
5
3
3
3
22
32
43
55
56
59
39
39
35
48
58
96
97
95
91
94
93
96
95
96
95
93
04:96
03:97
01:99
01:99
02:98
02:98
02:98
04:96
06:94
08:92
10:90
35:65
30:70
31:69
35:65
37:63
44:56
49:51
56:44
60:40
67:33
70:30
The irradiation of the less strained cis-1 cycloalkene in the
presence of benzophenone afforded mainly mixtures of the cis-2
and trans-2 oxetanes (cycloaddition), as is known for the cis-
* Address correspondence to this author. Fax: +49(0)931/888 4756.
E-mail: adam@chemie.uni-wuerzburg.de. Internet: www-organik.chemie.uni-
wuerzburg.de.
10
11
(1) (a) Griesbeck, A. G.; Fiege, M. In Molecular and Supramolecular
Photochemistry; Ramamurthy, V., Schanze, K. S., Eds.; Marcel Dekker: New
York, 2000; Vol. 6, p 33. (b) Adam, W.; Peters, K.; Peters, E.-M.; Stegmann,
V. R. J. Am. Chem. Soc. 2000, 122, 2958. (c) Bach, T. Synthesis 1998, 683.
(2) (a) Shima, K.; Sakai, Y.; Sakurai, H. Bull. Chem. Soc. Jpn. 1971, 44,
215. (b) Jones, G.; Khalil, Z. H.; Phan, X. T.; Chen, T. J.; Welankiwar, S.
Tetrahedron Lett. 1981, 22, 3823. (c) Shigemitsu, Y.; Yamamoto, S.;
Miyamoto, T.; Odaira, Y. Tetrahedron Lett. 1975, 2819. (d) Bryce-Smith,
D.; Evans, E. H.; Gilbert, A.; McNeill, H. S. J. Chem. Soc., Perkin Trans 1
1992, 485.
(3) (a) Adam, W.; Fro¨hling, B. Org. Lett. 2000, 2, 2519. (b) Mloston, G.;
Huisgen, R.; Huber, H.; Stephenson, D. S. J. Heterocycl. Chem. 1999, 36,
959. (c) Adam, W.; Weinko¨tz, S. J. Am. Chem. Soc. 1998, 120, 4861. (d)
Shea, K. J.; Kim, J.-S. J. Am. Chem. Soc. 1992, 114, 4846. (e) Beck, K.;
Hu¨nig, S.; Kla¨rner, F. G.; Kraft, P.; Artschwager-Perl, U. Chem. Ber. 1987,
120, 2041. (f) Gotthardt, K.; Kinzelmann, H. G.; Feist, U.; Buddrus, J. Chem.
Ber. 1986, 119, 2317. (g) Hartwig, J. F.; Jones, M.; Moss, R. A.; Lawrynowicz,
W. Tetrahedron Lett. 1986, 27, 5907. (h) Dehmlow, E. V.; Kramer, R. Angew.
Chem., Int. Ed. Engl. 1984, 23, 706. (i) Gilchrist, T. L.; Roberts, T. G. J.
Chem. Soc., Perkin Trans. 1 1983, 1283. (j) Inoue, Y.; Nishida, K.; Ishibe,
K.; Hakushi, T.; Turro, N. J. Chem. Lett. 1982, 471. (k) Bryce-Smith, D.;
Foulger, B.; Forrester, J.; Gilbert, A.; Orger, B. H.; Tyrell, H. M. J. Chem.
Soc., Perkin Trans. 1 1980, 55.
a-c See Table 1. d In view of the trans-1 isomerization to cis-1, the
conversions were kept as low as possible to minimize photocycload-
dition with cis-1 and thereby not falsify the dr values for trans-1.
e Benzpinacol (<5%) were also formed.
cyclooctene diastereomer with several carbonyl partners;2 also,
small amounts of benzpinacol (reduction) are formed. Striking,
however, is the marked temperature effect on the cis/trans
diastereomeric ratio (dr) of the oxetanes 2: While at -95 °C the
cis-2 oxetane is formed nearly (dr 98:2) exclusively (Table 1,
entry 1), both diastereomers are generated in about equal (dr 45:
55) amounts at -20 °C (Table 1, entry 5). At elevated temper-
atures, the trans-2 isomer dominates (entries 6-10) and levels
off (dr ∼20:80) at g80 °C (entries 10-12).
The strained trans-cyclooctene (trans-1) gave over a broad
temperature range (-80 up to 60 °C) the trans-2 oxetane nearly
exclusively (98 ( 2%) within the experimental error (Table 2,
entries 1-8). Only at temperatures higher than 60 °C was some
(up to 10%) cis-2 isomer observed (entries 9-11). Also cis-
cyclooctene (cis-1) was obtained as a significant isomerization
product of trans-1. The relative amount of cis-1 increased from
∼30% at the lower temperatures (entries 2 and 3) up to ∼70% at
(4) (a) Buschmann, H.; Scharf, H.-D.; Hoffmann, N.; Plath, M. W.; Runsink,
J. J. Am. Chem. Soc. 1989, 111, 5367. (b) Bach, T.; Jo¨dicke, K. Chem. Ber.
1993, 126, 2457. (c) Haddad, N.; Galili, N. Tetrahedron Lett. 1997, 38, 6083.
(d) Becker, D.; Cohen-Arazi, Y. J. Am. Chem. Soc. 1996, 118, 8278. (e) Inoue,
Y. Chem. ReV. 1992, 92, 741.
(5) Buschmann, H.; Scharf, H.-D.; Hoffmann, N.; Esser, P. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 477.
10.1021/ja005744r CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/16/2001