Photochemical studies on benzonorbornene derivatives: Medium effects and asymmetric induction

Article abstract of DOI:10.2174/157017809787003098

The photochemical behaviors of benzonorbornene derivatives were investigated in the solid state as well as in the solution. In acetonitrile solution, benzonorbornene derivatives underwent the Norrish type II reaction affording a ratio of 1:1 of cyclizatio

Full text of DOI:10.2174/157017809787003098

Letters in Organic Chemistry, 2009, 6, 41-43
41
Photochemical Studies on Benzonorbornene Derivatives: Medium Effects
and Asymmetric Induction
Chao Yang, Wujiong Xia*, Qian Chen, Xiao Zhang, Bing Li and Baoquan Gou
The Academy of Fundamental and Interdisciplinary Science, Harbin Institute of Technology, Harbin, Heilongjiang,
150080, State Key Laboratory of Applied Organic Chemistry, Lanzhou, Gansu, 730000, P. R. China
Received March 03, 2008: Revised September 30, 2008: Accepted October 09, 2008
Abstract: The photochemical behaviors of benzonorbornene derivatives were investigated in the solid state as well as in
the solution. In acetonitrile solution, benzonorbornene derivatives underwent the Norrish type II reaction affording a ratio
of 1:1 of cyclization and cleavage products, whereas in the solid state, the sole cyclization product was obtained. The
stereochemistry of the photoproducts was identified by the X-ray crystallography. Enantiomeric excesses of up to 97%
can be achieved through the use of the solid-state ionic chiral auxiliary method of asymmetric synthesis.
Keywords: Benzonorbornene, solid state, Norrish type II, enantiomeric excesses, asymmetric synthesis.
Unlike reactions in solution, atomic and molecular mo-
tions in the solid state are highly restricted imposed by the
crystal lattice which makes it possible to get high enanti-
oselectivies, and the differentiation in chemical behavior
compared with the reaction in solution. During the course
of our investigations on the solid-state photochemical reac-
tions [1], the benzonorbornene derivative 1 was synthe-
sized and its photochemical behavior was studied in the
solution as well as in the solid state. In acetonitrile solu-
tion, benzonorbornene derivative 1a was shown to undergo
the Norrish type II reaction affording a ratio of 1:1 of cy-
clization and cleavage products [2]. However, the cyclobu-
tants into chiral products, appeared to be ideal for studying
asymmetric induction in organic photochemistry, and mo-
tivated by the paucity of general methods of asymmetric
photochemical synthesis, we embarked on a program de-
signed to achieve this goal.
The starting material 1 chosen for study was synthe-
sized
from
commercially
available
1-bromo-2-
fluorobenzene and freshly cracked cyclopentadiene. The
[4ꢀ + 2ꢀ] cycloaddition of the above two compounds led to
the benzonorbornadiene, which was, according to the pro-
cedure we reported in the previous paper, treated with
bromine, KH/diisopropylamine and tert-Butyl Lith-
R
HO
R
R
ion
at
liz
c
y
c
hv
O
2
OH
a
R
bon
d a
eav
c
l
ag
e
a
R = COOMe
O
b
R = COOH
1
3
Scheme 1.
tanol 2b was obtained as the sole product when benzonor-
bornene derivative 1b was photolyzed in the solid state
(Scheme 1). These reactions, which convert achiral reac-
ium/CO2 sequentially to give the carboxylic acid [3]. The
target compounds 1a and 1b were obtained by conversion
of the carboxylic acid to the Weinreb amide [4], followed
by addition of the Grinard reagents respectively. A solution
of ketone 1a (267 mg, 0.87 mmol) in acetonitrile (40 mL)
was purged with N2 and irradiated (Pyrex filter, 450 W
Hanovia lamp) for 4.5 hours. Gas chromatography indi-
*Address correspondence to this author at the Academy of Fundamental
and Interdisciplinary Science, Harbin Institute of Technology, Harbin,
Heilongjiang, 150080, P. R. China; Fax: (86) 451 86403193;
Email: xiawj@hit.edu.cn
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

42
Letters in Organic Chemistry, 2009, Vol. 6, No. 1
Yang et al.
COO-
+NH3-R*
at the molar ratio of 1:1. Salts were photolyzed in the crys-
talline state in the same manner as the ketone 1b (Scheme
2). Following photolysis, the photoproducts were treated
with ethereal diazomethane, and the resulting methyl esters
were analyzed by chiral HPLC to obtain the enantiomeric
excess (ee) values and GC for the conversions. The results
of the enantiomeric excess determinations are summarized
in Table 1.
b
a
2a
1b
O
As can be seen in Table 1, the enantiomeric excess was
obtained as high as 97%. The poor enantioselectivity ob-
served for the salt of (1S,2S)-(+)-2-amino-1-phenyl-1,3-
propandiol can be attributed in part to conformational
enantiomerism since, in the crystalline state, the enanti-
omeric conformations exist as diastereomers and may
therefore have different rates of reactivity. Although the
salt of (R)-(+)-ꢀ-methylphenethylamine was seen to give
no observable photoreaction, there are some features of the
crystal structure deserving mention. From Fig. (1b), it is
clearly seen that the carbonyl oxygen atom lies closer to
one of the two diastereotopic ꢁ-hydrogens (the closer has
been Ha, the further Hb [6]). It is reasonable to assume that
all of the salts showing optical selectivity following solid
state photolysis crystallize in a similar manner. Therefore,
the observed enantioselectivity is due to a conformational
effect during crystallization rather than a direct influence
of the chiral auxiliary upon the reaction, or even the chiral
cavity created by the neighbouring molecules. Work is
ongoing in our laboratory to provide evidence for the chiral
auxiliary method being applied in synthetically useful
compounds.
4
Scheme 2.
cated that the reaction had proceeded to 91% conversion,
producing two primary photoproducts: 2 (46%) and 3
(52%). The structure and the stereochemistry of the photo-
products was identified by 1D, 2D NMR, IR, EI analysis,
and further by X-ray crystallographic method (Fig. 1a).
Gas chromatography with a mass selective detector con-
firmed the presence of small amounts of naphthalene and
p-carboxymethylacetophenone resulting from Norrish type
II cleavage of ketone 3 in a secondary photoreaction. When
conducting the solid state photolysis, 2-3 milligrams of the
crystalline ketone 1b were crushed between two glass mi-
croscope slides and sealed under a nitrogen atmosphere
within a polyethylene bag. After irradiation, the photopro-
ducts were treated with ethereal diazomethane and con-
verted into the corresponding methyl esters as 2 (>99%)
and 3 (trace) [5]. We speculated that there are two main
factors on the differentiation in the results obtained both in
solution and solid state. First, molecular conformation as
well as the conjugative effect with benzo- group has the
equal effect in the product formation, leading to the ratio of
1:1 of cyclization and cleavage products; while in the solid
state, the ketone was recrystallized in a conformation in
which cyclization is the preferred mode of reaction of the
biradicals formed by photolysis. Therefore, molecular con-
formation rather than conjugative effect affects the produc-
tion formation in the solid state.
ACKNOWLEDGEMENTS
We thank Dr. C. Scott and Brian O. Patrick for X-ray
crystallographic analysis. C.Y. and W.X. thank the finan-
cial support from the New Century Excellent Talent Pro-
gram of Chinese Ministry of Education (No.NCET-06-
0341 and NCET-07-0242). W. X. thanks the financial sup-
port from Science Foundation of Harbin City (No.
01310800),ꢀ program of excellent Team in HIT, China
NSFC (No. 20802013) and CSCSE (No. 01311065).
Now we turn to the asymmetric study aspect of the
work. The salts 4 for study were prepared by treatment of
carboxylic acid 1b with a variety of optically pure amines
Table 1. Asymmetric studies on salts 4 in the solid statea
Amine
Conversion (%)b
Ee (%)c
ꢀd
24
66
17
99
99
42
21
97
92
96
93
84
86
12
(R)-(+)-1-phenylethylamine
B
(S)-(-)-1-phenylethylamine
A
(S)-(-)-phenylalanine
A
B
B
(1R,2R)-(-)-pseudoephedrine
(1S,2S)-(+)-2-amino-1-
phenyl-1,3-propandiol
(R)-(+)-ꢀ-methylphenethylamine
3
-
-
b
aSamples were irradiated through Pyrex using a 450-W Hanovia medium-pressure mercury lamp. Conversion % based on GC. c Enantiomeric excesses were determined using a
Chiralpak® AS® HPLC column. dA refers to the first peak eluted in the HPLC analysis as the predominant enantiomer, B to the second.

Photochemical Studies on Benzonorbornene Derivatives
Letters in Organic Chemistry, 2009, Vol. 6, No. 1
43
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