Novel Enhancement of Diastereoselectivity of [2 + 2] Photocycloaddition of Chiral Cyclohexenones to Ethylene by Adding Naphthalenes

Article abstract of DOI:10.1021/jo0354746

The additive effect on the diastereoselective [2 + 2] photocycloaddition of chiral cyclohexenones 1 to ethylene is examined. A novel and fairly efficient method of increasing the diastereoselectivity in the reaction of 1a was elucidated. The de value increased from 56% to 83% by the addition of 1-phenylnaphthalene. The major product 2a was isolated by the recrystallization of the diastereomeric mixture (major/minor = 11/1), of which X-ray analysis confirmed the absolute configuration of the bicyclic system of 2a. Hydrolysis for removing the chiral auxiliary and subsequent esterification afforded the optically pure bicyclo[4.2.0]octanone derivative 5. From the fluorescence spectral analyses and other experimental results, the additive effect is attributed to the complex formation of chiral cyclohexenone 1a and added naphthalenes.

Full text of DOI:10.1021/jo0354746

Novel En h a n cem en t of Dia ster eoselectivity of [2 + 2]
P h otocycloa d d ition of Ch ir a l Cycloh exen on es to Eth ylen e by
Ad d in g Na p h th a len es
Ken Tsutsumi,* Hiroaki Nakano, Akinori Furutani, Katsunori Endou, Abdurshit Merpuge,
Takuya Shintani, Tsumoru Morimoto, and Kiyomi Kakiuchi*
Graduate School of Materials Science, Nara Institute of Science and Technology (NAIST),
8916-5 Takayama, Ikoma, Nara 630-0192, J apan
tsutsumi@ms.aist-nara.ac.jp
Received October 7, 2003
The additive effect on the diastereoselective [2 + 2] photocycloaddition of chiral cyclohexenones 1
to ethylene is examined. A novel and fairly efficient method of increasing the diastereoselectivity
in the reaction of 1a was elucidated. The de value increased from 56% to 83% by the addition of
1-phenylnaphthalene. The major product 2a was isolated by the recrystallization of the diastereo-
meric mixture (major/minor ) 11/1), of which X-ray analysis confirmed the absolute configuration
of the bicyclic system of 2a . Hydrolysis for removing the chiral auxiliary and subsequent
esterification afforded the optically pure bicyclo[4.2.0]octanone derivative 5. From the fluorescence
spectral analyses and other experimental results, the additive effect is attributed to the complex
formation of chiral cyclohexenone 1a and added naphthalenes.
In tr od u ction
method for asymmetric synthetic strategies may be
diastereodifferentiating photoreactions using chiral aux-
iliaries. From this viewpoint, we have studied the dias-
tereoselective [2 + 2] photocycloaddition of cyclohex-
enones having chiral auxiliaries with the smallest olefin,
ethylene, to give bicyclo[4.2.0]octanones.5 In this photo-
reaction, menthyl derivatives are effective auxiliaries in
achieving a higher degree of chiral induction. Lange,
Scharf, and other pioneering groups in this field reported
asymmetric inductions in [2 + 2] photocycloadditions,
which were limited to bulky olefins and relative low
chemical yields with moderate selectivities.6
Photochemical [2 + 2] cycloadditions have emerged as
valuable reactions in the construction of complex mol-
ecules.1 In addition, these reactions readily prepare a
framework for strained cyclobutane, which undergoes
transportation to additional structures by ring expansion
reactions.2 We previously reported on the acid-catalyzed
rearrangement of bicyclo[4.2.0]octanones, which were
readily prepared by the [2 + 2] photocycloaddition of
cyclohexenones to ethylene or allene, to give polyquinane-
type compounds and related applications to the synthesis
of various terpenoids.3 Despite these useful applications,
far less information about asymmetric photoreactions is
known than that for thermal ones.4,2e The most promising
We describe herein a new entry of naphthylmenthyl
to diastereoselective photoaddition as a chiral auxiliary
and the novel enhancement in selectivity by the addition
of naphthalenes. We also discuss the mechanistic study
related to the origin of the selectivity as well as the
insight of the additive effect.
* To whom correspondence should be addressed. Tel: +743-72-6084.
Fax: +743-72-6089.
(1) (a) Crimmins, M. T. Chem. Rev. 1988, 88, 1453. (b) Schreiber,
S. T. Science 1985, 227, 857. (c) Crimmins, M. T.; Reinhold, T. L. In
Organic Reactions; Paquette, L. A., Ed.; J ohn Wiley & Sons: New
York: New York, 1993; Vol. 44, p 297. (d) Winkler, J . D.; Bowen, C.
M.; Liotta, F. Chem. Rev. 1995, 95, 2003. (e) Bach, T. Synthesis 1998,
683.
(4) (a) Kagan, H. B.; Fiand, J . C. Top. Stereochem. 1978, 10. (b) Rau,
H. Chem. Rev. 1983, 83, 535. (c) Inoue, Y. Chem. Rev. 1992, 92, 741.
(d) Everitt, S. R. L.; Inoue, Y. In Organic Photochemistry; Molecular
and Supramolecular Photochemistry; Ramamurthy, V., Schanze, K.
S., Eds.; Marcel Dekker: New York, 1999; Vol.3, p 71. (e) Pete, J .-P.
In Advances in Photochemistry; Neckers, D. C., Volman, D. H., von
Bu¨nau, G., Eds.; J ohn Wiley & Sons: New York, 1996; Vol. 21, p 135.
(f) Griesbeck, A. G.; Meierihenrich, U. L. Angew. Chem., Int. Ed. 2002,
41, 3147.
(5) Tsutsumi, K.; Endou, K.; Furutani, A.; Ikki, T.; Akinori, Nakano,
H.; Shintani, T.; Morimoto, T.; Kakiuchi, K. Chirality 2003, 15, 504.
(6) (a) Lange, G. L.; Decicco, C.; Lee, M. Tetrahedron Lett. 1987,
28, 2833 and references therein. (b) Lange, G. L.; Decicco, C. P.
Tetrahedron Lett. 1988, 29, 2613. (c) Hoffmann, N.; Scharf, H.-D.;
Runsink, J . Tetrahedron Lett. 1989, 30, 2637 and references therein.
(d) Demuth, M.; Palomer, A.; Sluma, H. D.; Dey, K. D.; Kru¨ger, C.;
Tsay, Y.-H. Angew. Chem., Int. Ed. 1986, 25, 1117. (e) Sato, M.;
Takayama, K.; Furuya, T.; Noriyoshi, I.; Kaneko, C. Chem. Pharm.
Bull. 1987, 35, 3971.
(2) (a) Corey, E. J .; Mitra, R. B.; Uda, H. J . Am. Chem. Soc. 1964,
86, 485. (b) Corey, E. J .; Bass, J . D.; Lemahieu, R.; Mitra, R. B. J . Am.
Chem. Soc. 1964, 86, 5570. (c) Lange, G. L.; Merica, A.; Chimanikire,
M. Tetrahedron Lett. 1997, 38, 6371. (d) Namyslo, J . C.; Kaufmann,
D. E. Chem. Rev. 2003, 103, 1485-1537. (e) Lee-Ruff, E.; Mladenova,
G. Chem. Rev. 2003, 103, 1449-1483.
(3) The novel acid-catalyzed rearrangement of bicyclo[4.2.0]octanones
gave various terpenoids having polyquinane skeletons, such as (()-5-
oxosilphiperfol-6-ene, (()-silphiperfol-6-ene, (()-3-oxosilphinene, and
(()-tetramethylmediterraneol B; see: (a) Kakiuchi, K.; Ue, M.; Tsu-
kahara, H.; Shimizu, T.; Miyao, T.; Tobe, Y.; Odaira, Y.; Yasuda, M.;
Shima, K. J . Am. Chem. Soc. 1989, 111, 3707. (b) Ue, M.; Ohnishi, Y.;
Kobiro, K.; Kakiuchi, K.; Tobe, Y.; Odaira, Y. Chem. Lett. 1990, 149.
(c) Kakiuchi, K.; Nakamura, I.; Matsuo, F.; Nakata, M.; Ogura, M.;
Tobe, Y.; Kurosawa, H. J . Org. Chem. 1995, 60, 3318 and references
therein. (d) Kakiuchi, K.; Horiguchi, T.; Minato, K.; Tobe, Y.; Kurosawa,
H. J . Org. Chem. 1995, 60, 6557.
10.1021/jo0354746 CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/08/2004
J . Org. Chem. 2004, 69, 785-789
785

Tsutsumi et al.
SCHEME 1
a more effective chiral auxiliary than was (-)-8-(phenyl)-
menthyl (Table 1, entries 3 and 4).
The 56% de (Table 1, entry 3) was a good result for
asymmetric photochemistry, but not high enough to be
applicable to asymmetric synthesis. It is usually difficult
to control the regio- and/or stereochemistry in photo-
chemical reactions via a highly energetic and short-lived
photoexcited state. Interestingly, we discovered a sig-
nificant increase in de (from 56% to 71%) by the addition
of naphthalene (10 equiv based on 1a ) (Table 1, entry
5). This additive effect was observed when adding 5 equiv
of naphthalene but barely observable when adding 1
equiv (Table 1, entries 6 and 7). In the presence of
1-cyanonaphthalene, the de value increased to 76-81%.
At the higher reaction temperatures, the de values
increased by adding 1-cyanonaphthalene, but the reaction
proceeded very slowly at 0 °C (Table 2, entries 1, 11, and
12). In comparison with 1a , there was no additive effect
on 1b using 1-cyanonaphthalene as an additive (Table
2, entry 13). The irradiation of 1a in the presence of other
naphthalene derivatives afforded good yields (95-99%)
of the diastereomeric mixture of 2a with high diastereo-
selectivity (de ) 77-83%; Table 1, entries 14-16). The
diastereoselectivity increased with the use of the substi-
tuted naphthalenes, but any correlation between the de
and the nature of the naphthalenes was not clear. The
addition of naphthalenes in the reaction solution is an
easy and effective method for increasing diastereoselec-
tivity, which is first reported here on the photo- or
thermal-reactions using chiral auxiliaries. The presented
method needs 10 equiv of a naphthalene derivative as
the additive, but the added naphthalenes were separated
easily from the photoadducts by the standard column
chromatographycally technique on silica gel. The mecha-
nistic study of the additive effect is discussed based on
the above experimental results and some spectral aspects
(vide infra).
TABLE 1. Dia ster eoselective [2 + 2] P h otocycloa d d ition
of 1a ,b to Eth ylen ea
T
time yieldc
%
entry R*
additive (equivb)
(°C) (h)
(%) ded
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
1a
1a
1a
1b
0
-40
-78 1.5
-78 1.5
-78 1.5
-78 1.5
-78 1.5
-78
-78 1.5
-78
-40
0
-78 1.5
-78 1.5
2
2
96
96
89
84
91
95
99
94
85
94
99
17e
99
99
95
95
47
55
56
40
71
70
58
76
81
81
72
57
40
79
77
83
1a naphthalene (10)
1a naphthalene (5)
1a naphthalene (1)
1a 1-cyanonaphthalene (5)
1a 1-cyanonaphthalene (10)
1a 1-cyanonaphthalene (20)
1a 1-cyanonaphthalene (10)
1a 1-cyanonaphthalene (10)
1b 1-cyanonaphthalene (10)
1a 2-cyanonaphthalene (10)
2
3
4
5
1a 1-methoxynaphthalene (10) -78 1.5
1a 1-phenylnaphthalene (10)
-78
3
a
b
Pyrex filter, 500-W high-pressure Hg lamp. Based on 1.
c Isolated yield by column chromatography on SiO2. Determined
d
by 1H NMR. e 20% conversion for 5 h.
Resu lts a n d Discu ssion
Isola tion of th e Op tica lly P u r e Bicyclo[4.2.0]-
octa n on e 5. None of the isomers of 2a could be separated
by the standard column chromatographycally technique
on silica gel or alumina. But recrystallization of the oily
diastereomeric mixture (major/minor ) 11/1) in CH2Cl2-
hexane solution afforded a crystalline solid. When the
major/minor ratio of the diastereomeric mixtures was less
than 11/1, no solid was generated by the similar recrys-
tallization technique. The repeated recrystallization of
the obtained solid gave single crystals, which were
confirmed to be the pure major isomer by NMR analysis
(> 98% de). By adding a very small amount of the single
crystal as a seed in the saturated solution, the crystals
were afforded as the major isomer more effectively
through a self-similar crystal-growth process. Three-
times recrystallization in the presence of the single
crystals afforded the pure major isomer of 2a (> 98% de)
in 56% yield from the diastereomeric mixture of 2a
(major/minor ) 11/1). The pure isomer of 2a was hydro-
lyzed to remove the chiral auxiliary and the esterification
of the obtained bicyclo[4.2.0]octanone carboxylic acid 3
with diazomethane afforded methyl ester 5 in 75% yield
(two steps) (Scheme 2). From the organic layer of the
hydrolysis, 8-(2-naphthyl)menthol 4 was recovered in
97% yield, which suggests the possibility of the recycling
4 as a chiral auxiliary. GC analysis using a chiral column
(CHIRALDEX G-TA) indicated that 5 was optically pure
Dia ster eoselective [2 + 2] P h otocycloa d d ition s.
We prepared the new chiral cyclohexenone 1a containing
the (-)-8-(1-naphthyl)menthyl group,7 which is expected
to shield an diastereoface of cyclohexenyl ring more
effectively than the (-)-8-(phenyl)menthyl one. The pho-
toreactions were carried out by irradiation with light
through Pyrex (λ > 280 nm) from a 500-W high-pressure
mercury lamp in a solution of cyclohexenone carboxylate
derivative 1 saturated with ethylene (Scheme 1). Initially,
photocycloaddition of 1a with ethylene at 0 °C gave a
diastereomeric mixture of adduct 2a in excellent yield,
which was purified by flash chromatography. The 1H
NMR spectrum of the mixture of 2a shows two separate
sets of resonance of the methyne protons at δ 2.70 and δ
2.54. The diastereomeric excess (de) of adduct 2a was
determined to be 47% by comparing the areas of their
two signals, as shown in Table 1, entry 1. Subsequently,
a gradual increase in the de’s was observed at lower
temperatures without any decrease in yield (Table 1,
entries 1-3). The (-)-8-(1-naphthyl)menthyl group was
(7) (-)-8-(2-Naphthyl)menthol was prepared according to the lit-
erature procedure; see: (a) Ort, O. In Organic Synthesis; Freeman, J .
P., Ed.; J ohn Wiley & Sons: New York, 1993; Vol. 8, p 522. (b)
Hagiwara, H.; Akama, T.; Okano, A.; Uda, H. Chem. Lett. 1989, 2149.
(c) Potin, D.; Dumas, F.; Maddaluno, J . Synth. Commun. 1990, 20,
2805.
786 J . Org. Chem., Vol. 69, No. 3, 2004

Diastereoselective [2 + 2] Photocycloaddition
SCHEME 2a
a
Reagents: (i) NaOH, DMSO, 110 °C (4: 97%); (ii) CH2N2, Et2O
F IGURE 2. UV-vis spectra in CH2Cl2 at 25 °C (cell length:
1 cm): (a) 1a (1.0 × 10-4 M); (b) 1-cyanonaphthalene (1.0 ×
10-4 M); (c) 1-cyanonaphthalene (1.0 × 10-4 M) + 1a (1.0 ×
10-4 M).
(75%, two steps).
F IGURE 1. X-ray structures of 1a and 2a .
and a specific optical rotation could be measured ([R]22.2
D
F IGURE 3. CD spectra in CH2Cl2 at -78 °C (cell length: 1
cm): (d) 1-cyanonaphthalene (1.0 × 10-4 M) + 1a (1.0 × 10-4
M); (e) 1a (1.0 × 10-4 M).
) +169.8, c ) 0.08 in CH2Cl2). The absolute configuration
of 5 was not directly proven, but we confirmed the (1S,6S)
stereochemistry of a bicyclic system from the X-ray
crystallography analysis of 2a (vide infra).
X-r a y Cr ysta llogr a p h ic An a lyses of 1a a n d 2a . A
single-crystal X-ray crystallographic analysis of 1a es-
tablished the stacked conformation, where the cyclohex-
enone and the naphthyl ring are face-to-face (Figure 1,
1a ). Such a stacked conformation might imply a π-stack-
ing interaction between the naphthyl ring and the
cyclohexenone-ester moiety. The crystal structure of 1a
reveals the s-trans conformer between the ester carbonyl
group and the double bond involved in the cyclohexane
ring, which may be the most stable conformer in solution
state. The absolute configuration of 2a (major isomer)
was proven by the single-crystal X-ray analysis (Figure
1, 2a ), which indicated that it has the (1S,6S) stereo-
chemistry of a bicyclic system. The configuration of the
chiral centers generated in the reaction is consistent with
the addition to the Si-face of the cyclohexenone ring.
From these X-ray structures, it is reasonable to assume
that ethylene approaches from the less shielded Si-face
of the cyclohexenyl group of 1a to yield the major product
2a . The experimental de’s in Table 1 and the structural
property reveal that the bulky and electron-rich naph-
thalene backbone is more efficient in diastereoface dif-
ferentiation than the benzene one of 1b.
F IGURE 4. Fluorescence spectra upon excitation at 297 nm
in CH2Cl2 at -78 °C: (f) 1-cyanonaphthalene (0.05 M); (g)
1-cyanonaphthalene (0.05 M) + 1a (0.05 M); (h) 1-cyanonaph-
thalene (0.05 M) + (-)-8-(2-naphthyl)menthol (0.05 M).
scopy analyses for 1a , 1-cyanonaphthalene, and a mix-
ture of 1-cyanonaphthalene and 1a , respectively. How-
ever, new absorption band, based on CT complex of
1-cyanonaphthalene and 1a , was not observed (Figure
2). In addition, the CD spectrum of a mixture of 1-cy-
anonaphthalene and 1a did not also show the interaction
clearly by comparison with the spectrum of 1a (Figure
3). We confirmed such interaction by fluorescence spec-
tral analyses of 1a and some components (Figure 4).
Excitation (λex ) 297 nm)8 of 1-cyanonaphthalene (0.05
M) in CH2Cl2 at -78 °C emitted fluorescences at 347 and
424 nm resulting from the monomer and the excimer,
respectively (Figure 4f). The fluorescence at 424 nm was
not observed clearly at 25 °C or for the 0.01 M solution.
The intensity of the emissions of 1-cyanonaphthalene
decreased as 1a was added, but no new fluorescence,
In ter m olecu lar In ter action between 1a an d Added
Na p h th a len es. The higher induction requires both
diastereoface selectivity and a fixed orientation of the
cyclohexenone ring in the transition state. Supposing that
the diastereoselectivity consists of the population of
stacked conformation as shown in Figure 1, the additive
effect might stabilize such a conformer. Since the additive
effects were observed for 1a but not for 1b, the added
naphthalenes interact with the naphthyl moiety attached
to the menthyl group. We carried out UV-vis spectro-
(8) The UV-vis spectra of 1-cyanonaphthalene in CH2Cl2 show the
π, π* aromatic absorption at 297 nm (ꢀ ) 8811), while for 1a a weak
absorption band was observed at 297 nm (ꢀ ) 885). See Figure 2.
J . Org. Chem, Vol. 69, No. 3, 2004 787

Tsutsumi et al.
dried (MgSO4) and concentrated in vacuo. The residue was
purified by flash chromatography (AcOEt/hexane, 1/9) to give
the ester 1a (1.08 g, 88%) as a colorless solid: mp 118.0-119.7
CHART 1
°C; [R]20.0 ) -61.2, c ) 2.0 in CH2Cl2; 1H NMR (400 MHz,
D
CDCl3) δ 7.73 (d, J ) 9.5 Hz, 1H), 7.68 (d, J ) 8.8 Hz, 2H),
7.50 (m, 2H), 7.36 (m, 2H), 5.87 (s, 1H), 5.06 (td, J ) 11.0, 4.4
Hz, 1H), 2.25 (td, J ) 12.5, 3.7 Hz, 1H), 2.04 (dd, J ) 13.9, 3.7
Hz, 1H), 1.81-1.20 (m, 16H), 1.14-0.95 (m, 2H), 0.90 (d, J )
6.6 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 200.71 (s), 165.91
(s), 150.27(s), 148.38 (d), 134.25 (s), 132.47 (s), 132.16 (s),
128.47 (d), 128.36 (d), 128.12 (d), 126.58 (d), 125.95 (d), 125.90
(d), 122.74 (d), 75.12 (d), 50.53 (d), 42.52 (t), 40.26 (t), 37.62
(s), 35.20 (t), 32.07 (q), 31.36 (q), 26.77 (t), 24.54 (d), 22.55 (t),
based on the exciplex of 1-cyanonaphthalene and 1a , was
observed (Figure 4g). The emissions might have been
quenched by the absorption of the excitation light at 297
nm by the added 1a or by the intramolecular interaction
between the naphthyl ring and the enone ester moiety.9
In contrast, for the mixture of 8-(2-naphthyl)menthol and
1-cyanonaphthalene, a new exciplex fluorescence ap-
peared at 435 nm (Figure 4h). These spectral results and
the photocycloaddition might lead to a new understand-
ing of the complex formation (naphthyl ring of 1a /added
naphthalene derivative) as illustrated in Chart 1. The
increase of de’s is considered the result of the fixed
conformation and the increased steric hindrance for the
approach of ethylene caused by such a complex formation.
22.13 (q), 22.01 (t); IR (KBr) 2949, 1714, 1685, 1252, 1227 cm-1
;
HRMS (EI) m/z calcd for C27H32O3 404.2351, found 404.2351;
UV-vis (CH2Cl2) λ ) 320 nm (ꢀ ) 393, CdO), see Figure 2.
Gen er a l P r oced u r e for P h otor ea ction of 1 to Eth yl-
en e. Irradiation reactions were carried out using a Pyrex flask
(>280 nm) in a water-cooled quartz immersion apparatus
using a HALOS 500-W Hg high-pressure UV lamp as the light
source. A 0.05 M solution of 1 and naphthalenes (0.05 M) in
CH2Cl2 was purged with ethylene at 25 °C for 5 min and
irradiated at each temperature without continuous purging
until 1 was nearly completely consumed. The reaction was
monitored by TLC and GLC. After the solvent evaporated, the
residue was purified chromatographically to give a diastereo-
meric mixture of photoadduct 2 along with the recovery of
naphthalenes. Each isomer of 2 could not be separated by
standard chromatographic purification, and therefore the de
value was not affected by this process. The de value of 2 was
determined by 1H NMR spectroscopy. The results are sum-
marized in Table 1, along with reaction conditions.
(1R,2S,5R)-5-Meth yl-2-[1-m eth yl-1-(2-n a p h th yl)eth yl]-
cycloh exyl (1S,6S)- a n d (1R,6R)-Bicyclo[4.2.0]octa n -2-
on e-6-ca r boxyla te (2a ). The photoreaction of 1a (40.5 mg,
0.10 mmol) in the presence of 1-phenylnaphthalene at -78 °C
in CH2Cl2 for 1.5 h gave a diastereomeric mixture of 2a (41.1
mg, 95%) after chromatography (AcOEt/hexane, 1/9). The de
was determined to be 83% by 1H NMR spectroscopy. 2a :
Colorless oil; 1H NMR (500 MHz, CDCl3) δ for the major
diastereomer (values in parentheses are distinct signals as-
signed to the minor diastereomer) 7.75-7.69 (m, 3H), (7.60)
7.59 (s, 1H), 7.45 (d, J ) 8.5 Hz, 1H), 7.38-7.31 (m, 2H), 4.93
(m, 1H), 2.70 (2.54) (dd, J ) 9.2, 7.3 (9.2) Hz, 1H), 2.18-2.05
(m, 2H), 1.96-1.19 (m, 13H), (1.40) 1.39 (s, 3H), (1.22) 1.21 (s,
3H), 1.12-1.03 (m, 1H), 0.98-0.91 (m, 1H), 0.86-0.78 (m, 4H);
13C NMR (126 MHz, CDCl3) δ for the major diastereomer
(values in parentheses are distinct signals assigned to the
minor diastereomer) 212.46 (211.11) (s), 174.61 (174.48) (s),
148.61 (148.51) (s), 132.99 (s), (131.24) 131.13 (s), 127.44 (d),
(127.25) 127.13 (d), 126.92 (d), 125.43 (d), 124.80 (d), 124.45
(d), 122.19 (d), (74.58) 74.54 (d), 48.93 (48.88) (d), 47.81 (47.72)
(s), 45.21 (d), (41.37) 41.24 (t), (39.50) 39.47 (s), (38.16) 38.09
(t), 30.80 (d), (29.55) 28.96 (t), 27.73 (t), 27.55 (27.37) (q),
(26.34) 26.30 (t), (25.13) 24.84 (q), 21.40 (q), 20.66 (20.30) (t),
(20.25) 20.03 (t); IR (neat) 2952, 1712, 1239 cm-1; HRMS (EI)
m/z calcd for C29H36O3 432.2664, found 432.2662.
Con clu sion
In conclusion, we demonstrated that in the diastereo-
selective [2 + 2] photocycloaddition of chiral cyclohex-
enone carboxylates to ethylene, the (-)-8-(2-naphthyl)-
menthyl group was an effective chiral auxiliary in this
reaction, proof of which was supported by X-ray analysis.
We also discovered a novel and fairly efficient method of
increasing diastereoselectivity by the addition of naph-
thalenes. The additive effect is attributed to the complex
formation of 1a and naphthalenes, which was supported
by the fluorescence spectra. Moreover, recrystallization
of the photoadduct 2a afforded the diastereomerically
pure major isomer (> 98% de). Removing the chiral
auxiliary gave the optically pure bicyclo[4.2.0]octanone
derivative 5, of which the absolute configuration of the
bicyclic system was elucidated from the X-ray analysis
of the major cycloadduct.
Exp er im en ta l Section
Syn t h esis of Ma t er ia ls. (-)-(1R,2S,5R)-5-Methyl-2-(1-
methyl-1-phenylethyl)cyclohexylcyclohexen-3-one-1-carboxyl-
ate (1b) and cyclohexen-3-one-1-carboxylic acid were prepared
according to the literature procedure7 and reported in ref 5.
(1R,2S,5R)-(-)-8-(2-Naphthyl)menthol was prepared according
to literature procedures.7b,c
(-)-(1R,2S,5R)-5-Meth yl-2-[1-m eth yl-1-(2-n a p h th yl)eth -
yl]cycloh exylcycloh exen -3-on e-1-ca r boxyla te (1a ). To a
mixture of cyclohexen-3-one-1-carboxylic acid (0.43 g, 3.05
mmol), (-)-8-(2-naphthyl)menthol (0.86 g, 3.05 mmol, [R]20.0
(1S,6S)-Bicyclo[4.2.0]oct a n -2-on e-6-ca r b oxylic Acid
Meth yl Ester (5). Recrystallization of the diasteromeric
mixture of 2a (major/minor ) 11/1) from CH2Cl2-hexane gave
a crystalline solid, and similar recrystallizations of the ob-
tained crystals were carried out several times to give a few
pure major isomer of 2a as colorless single crystals. In the
presence of a small amount of the single crystals, 3× recrys-
tallization of the diastereomeric mixture of 2a (205.3 mg;
major/minor ) 11/1) from CH2Cl2-hexane afforded the dias-
tereomerically pure major isomer (> 98% de, 108.6 mg, 53%
yield). Optical rotation of the obtained major isomer was
D
) -2.5, c ) 0.99 in EtOH), and (dimethylamino)pyridine (0.37
mg, 3.05 mmol) in dry CH2Cl2 (4 mL) was added 1,3-dicyclo-
hexylcarbodiimide (1.89 g, 9.14 mmol) at 0 °C. The reaction
mixture was stirred at 0 °C for 5 min and at room temperature
for 14 h. The precipitated dicyclohexylurea was removed by
filtration through a glass filter, and the resulting filtrate was
washed with 0.5 N HCl and an aqueous, saturated solution of
NaHCO3. During this procedure, additional precipitated di-
cyclohexylurea was again removed by the filtration of both
layers to facilitate their separation. The organic solution was
measured ([R]22.7 ) +86.3, c ) 0.02 in CH2Cl2).
D
To a solution of the major isomer of 2a (18.0 mg, 0.042
mmol) in 2.0 mL of degassed DMSO was added 0.10 mL of
1.0M NaOH aq, and the reaction mixture was stirred at 110
(9) Similar photophysical intramolecular quenching of R-carbonyl
8-phenylmenthyl ester: Whitesell, J . K.; Younathan, J . N.; Hurst, J .
R.; Fox, M. A. J . Org. Chem. 1985, 50, 5499.
788 J . Org. Chem., Vol. 69, No. 3, 2004

Diastereoselective [2 + 2] Photocycloaddition
°C under nitrogen atmosphere for 2 h. After removal of DMSO
under reduced pressure, the reaction mixture was poured into
10 mL of H2O and extracted with 3 × 20 mL of Et2O. The
aqueous layer was separated, and the combined organic layers
were washed with saturated NaCl aq, dried over anhydrous
MgSO4, and concentrated in vacuo. The residue was purified
by flash chromatography (AcOEt/hexane, 1/9) to give (-)-8-
(2-naphthyl)menthol (11.8 mg, 97%) as a colorless solid. The
separated aqueous layer was treated with 10% HCl aq (pH 1)
and extracted with 3 × 20 mL of Et2O. The combined organic
layers were washed with saturated NaCl aq, dried over
anhydrous MgSO4, and concentrated in vacuo. The residue was
resolved in 0.5 mL of Et2O and treated with an ethereal
solution in diazomethane until a yellow color persisted. After
20 min, excess diazomethane was quenched by the addition
of a few drops of AcOH. The reaction mixture was concentrated
in vacuo, and the residue was purified by flash chromatogra-
phy (AcOEt/hexane, 1/9) to afford 6.0 mg (75%; 2 steps) of 5
Z ) 4, a ) 15.5081(3) Å, b ) 21.0872(4) Å, c ) 7.0796(1) Å, V
) 2315.18(8) Å3, Fcalcd ) 1.161 g cm-3. Of 10 848 reflections up
to 2θ ) 55.0°, 2942 were independent (Rint ) 0.016) and 2913
with I > 2σ(I). The structure was solved with direct methods
and refined with full matrix against all F2 data. Hydrogen
atoms were calculated in “riding” positions. wR ) 0.097 and
R ) 0.072. 2a : C29H36O3, colorless crystal (0.25 × 0.25 × 0.17
mm), orthorhombic, space group P212121 (#19), Z ) 4, a )
11.0801(9) Å, b ) 20.731(2) Å, c ) 10.8500(9) Å, V ) 2492.2(4)
Å3, Fcalcd ) 1.153 g cm-3. Of 18 945 reflections up to 2θ ) 55.0°,
3221 were independent (Rint ) 0.055) and 3218 with I > 2σ(I).
The structure was solved and refined in an analogous manner
to 1a . wR ) 0.088 and R ) 0.071.
Ack n ow led gm en t. We thank Mr. F. Asanoma for
his assistance in obtaining the X-ray analyses and Ms.
Y. Nishikawa for obtaining the HRMS. This work was
supported by a Grant-in-Aid for Scientific Research on
Priority Areas (417) from the Ministry of Education,
Culture, Sports, Science and Technology (MEXT) of the
J apanese Government.
as a colorless oil: [R]22.2 ) +169.8, c ) 0.08 in CH2Cl2; 1H
D
NMR (500 MHz, CDCl3) δ 3.72 (s, 3H), 3.28 (t, J ) 9.15 Hz,
1H), 2.52-2.22 (m, 4H), 2.18-1.80 (m, 6H); 13C NMR (126
MHz, CDCl3) δ 212.17 (s), 176.42 (s), 52.31 (d), 48.45 (s), 46.43
(q), 38.99 (t), 30.62 (t), 28.80 (t), 21.29 (t), 20.97 (t); IR (neat)
2952, 1729 cm-1; HRMS (EI) m/z calcd for C10H14O3 182.0943,
found 182.0944.
Cr ysta l Str u ctu r e An a lysis. Measurements were made
on a Rigaku RAXIS-RAPID Imaging Plate diffractometer with
Mo KR radiation at 296 K. 1a : C27H32O3, yellow crystal (0.40
× 0.10 × 0.10 mm), orthorhombic, space group P212121 (#19),
Su p p or tin g In for m a tion Ava ila ble: The crystallographic
data for 1a and 2a (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
J O0354746
J . Org. Chem, Vol. 69, No. 3, 2004 789