Asymmetric synthesis of tricyclic tetralin derivatives via an intramolecular photoreaction

Article abstract of DOI:10.1016/j.tet.2007.04.072

An intramolecular photoreaction for the synthesis of tricyclic tetralin derivatives through a Norrish/Yang type cyclization is described. Asymmetric studies on this reaction using ionic chiral auxiliaries gave enantiomeric excesses of up to 99% at conversions?of?80%, and the reaction mechanism was mapped out by a single crystal-to-single crystal reaction.

Full text of DOI:10.1016/j.tet.2007.04.072

Tetrahedron 63 (2007) 6791–6795
Asymmetric synthesis of tricyclic tetralin derivatives
via an intramolecular photoreaction
b,
Chao Yang,a Wu Jiong Xiaa, and John R. Scheffer
*
*
aResearch Academy of Science and Technology, Harbin Institute of Technology, Harbin, 150080 Heilongjiang, PR China
bDepartment of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1
Received 3 January 2007; revised 23 April 2007; accepted 24 April 2007
Available online 4 May 2007
Abstract—An intramolecular photoreaction for the synthesis of tricyclic tetralin derivatives through a Norrish/Yang type cyclization is
described. Asymmetric studies on this reaction using ionic chiral auxiliaries gave enantiomeric excesses of up to 99% at conversions of 80%,
and the reaction mechanism was mapped out by a single crystal-to-single crystal reaction.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
Yang cylization reaction.8 Based on 1D and 2D NMR spec-
tra as well as IR and MS, this photoproduct was assigned the
cis-ethyl, hydroxyl-containing structure, and the stereo-
chemistry was further confirmed by X-ray crystallography
described in the following section. Hyperchem MM3 calcu-
Tricyclic tetralin derivatives are important building blocks
for the synthesis of a wide variety of indole-diterpenes.1 Syn-
thesis of such compounds has become a challenge owing to
their strained ring systems and has attracted much attention
from chemists. A literature survey shows that the existing
methodologies include SmI2 mediated reaction,2 radical
addition reactions,3 metal-mediated reactions,4 and intermo-
lecular [2+2] photoadditions.5 Despite these advances, room
still exists for developing alternative and environmentally
friendly approaches to the synthesis of such compounds.
As part of our interest in solid-state photochemistry,6 we
developed a new approach to the asymmetric synthesis of tri-
cyclic tetralin derivatives via an intramolecular photore-
action. In this paper, we present what we have achieved in
this regard.
˚
lations showed that the C]O/Hg distance is 2.71 A, which
˚
is within the 2.72ꢀ0.2 A range established for successful
g-hydrogen abstraction in the solid state.9 Furthermore,
the photochemical procedure converts an achiral reactant
to a chiral product, which is suitable for asymmetric studies
using the ionic chiral auxiliary method.
CH2N2,
O
O
1. NaH, EtI, THF
2. CH2N2 Workup
Et2O
COOCH3
OH
COOH
2
1
O
hv
CH3CN
COOCH3
COOCH3
2. Results and discussion
3 (49% 2 steps)
Scheme 1.
4 (66% isolated yield)
Our strategy for the synthesis of tricyclic tetralin compounds
started from the commercially available 5-oxo-5,6,7,8-tetra-
hydronaphthalene-2-carboxylic acid 1 (Scheme 1), which
was treated with diazomethane in diethyl ether and reacted
with ethyl iodide and NaH to give diethyl tetralone 3 in
49% yield (two steps from 1 to 3). Irradiation of compound
3 in acetonitrile through Pyrex using a 450 W medium-pres-
sure mercury lamp successfully afforded tricyclic tetralin
compound 4 in 66% yield7 via an intramolecular Norrish/
Next we turned to the asymmetric synthesis aspect of the
work. Diethyl tetralone 3 was hydrolyzed with LiOH in
THF/H2O to give carboxylic acid 5 in 98% yield (Scheme
2). The next step was to introduce internal chiral auxiliaries
to compound 5 for asymmetric studies. Therefore, carbox-
ylic acid 5 was treated with a variety of optically pure amines
to form the corresponding ammonium carboxylate salts 6.
Such salts are required to crystallize in chiral space groups,
which provide the asymmetric environment responsible for
chiral induction. Crystals of these salts (2–5 mg) were
* Corresponding authors. Tel.: +86 451 86266993; fax: +86 451 86402588
(W.J.X.); tel.: +1 604 8223496; fax: +1 604 8222849 (J.R.S.); e-mail
addresses: xiawj@hit.edu.cn; scheffer@chem.ubc.ca
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.04.072

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C. Yang et al. / Tetrahedron 63 (2007) 6791–6795
O
O
COOH
COO- H3N+ R∗
a
b
c
3
4
6
5
Scheme 2. (a) LiOH, THF/H2O, 98%; (b) R*–NH2; (c) hn, solid state, CH2N2.
crushed between two Pyrex microscope slides, sealed in
polyethylene bags under nitrogen, and irradiated with
a 450 W medium-pressure mercury lamp. Following photo-
lysis, the photoproducts were treated with ethereal diazo-
methane, 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.
a large amplitude rotation of the aryl group, which is topo-
chemically forbidden in the solid state. Therefore, the enan-
tioselectivity of the reaction is governed by the homochiral
conformation favorable for formation of a single enantiomer
of the product.
A bonus was the finding that one of the reactions was a single
crystal-to-single crystal process,11 which allowed the crystal
structures to be obtained at the beginning, mid point and the
end of the reaction and an absolute configuration correlation
to be established between reactant and product. In the case of
the (S)-(ꢁ)-1-p-tolylethylammonium salt, the photoreaction
in the solid state was found to be a single crystal-to-single
crystal process, which allowed the structure of the 20% re-
acted crystal to be obtained.12 Figure 2 shows an ORTEP
representation of the 20% reacted crystal structure with the
chiral auxiliary omitted for clarity. In this figure the gray
lines belong to the reactant and the black lines belong to
the photoproduct. The mixed crystal structure shown in Fig-
ure 2 proves that abstraction of the closer hydrogen (Ha) is
favored over abstraction of Hb. Because the absolute config-
uration of the ionic chiral auxiliary is known, the absolute
configurations of the reactant and the product are estab-
lished, which allow us to state with certainty that abstraction
of Ha led to the product with the (R)-configuration at C1
as deduced from the crystal structure of the (S)-(ꢁ)-1-p-
tolylethylammonium salt. As can be seen, there is a close
correspondence in size and shape between reactant and
photoproduct, a common feature of nearly all single crystal-
to-single crystal transformations.
As can be seen in Table 1, the enantiomeric excess values ob-
tained for photoproduct 4 ranged from 7.4% to 99%. For the
salts studied, there was a decline in the photoproduct ee with
increasing conversion, which is presumably due to the
breakdown in the crystal lattice when the photoproduct re-
places the reactant. Fortunately, this could be compensated
by lowering the reaction temperature to ꢁ43 ꢂC. At temper-
atures much below ꢁ43 ꢂC, the solid-state photoreaction
became sluggish. As expected for a well-behaved system,
the use of (S)-(ꢁ)- and (R)-(+)-phenylethylamine led to the
optical antipodes of photoproduct 4.
To rationalize the enatioselective results observed in the
solid state, the X-ray crystal structure of the (S)-(ꢁ)-1-p-tol-
ylethylammonium salt was determined and is represented in
Figure 1.10 Under the influence of the chiral auxiliary, (S)-
(ꢁ)-1-p-tolylethylamine, the reactant crystallized in a homo-
chiral conformation in which the distance between the
˚
carbonyl oxygen and the g-hydrogen Ha (O/Ha, 2.69 A)
˚
is much closer than O/Hb (4.70 A). As a result, bond for-
mation between C1 and Ca is favored, affording one enantio-
mer of photoproduct 4. In contrast, formation of the optical
antipode of the photoproduct obtained by abstraction of
Hb and bonding between C1 and Cb is not only unlikely
on distance grounds, but following abstraction, also requires
To conclude, we have developed a new and convenient
approach to the synthesis of highly enantiomerically en-
riched tricyclic tetralin derivatives. Current efforts in our
Table 1. Asymmetric studies on the irradiation of salts 6 in the solid statea
Amine
Temperature
Conversionb (%)
ee (%)
ac
(S)-(ꢁ)-1-p-Tolylethylamine
ꢁ43 ꢂC
100
80
100
98
99
97
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
+
+
+
Room temperature
Room temperature
(S)-(ꢁ)-1-Cyclohexyl-ethylamine
(S)-(ꢁ)-1-Phenylethylamine
(R)-(+)-1-Phenylethylamine
ꢁ43 ꢂC
87
90
54
88
65
77
Room temperature
Room temperature
ꢁ43 ꢂC
51
35
74
86
62
58
Room temperature
Room temperature
ꢁ43 ꢂC
66
44
75
59
56
44
ꢁ
ꢁ
ꢁ
+
+
+
Room temperature
Room temperature
(R)-(+)-b-Methylphenylethylamine
ꢁ43 ꢂC
23
62
77
21
9.4
7.4
Room temperature
a
Samples were irradiated through Pyrex using a 450-W Hanovia medium-pressure mercury lamp.
Conversion % based on GC.
Sign of rotation of major enantiomer of photoproduct 4 at the sodium D-line.
b
c

C. Yang et al. / Tetrahedron 63 (2007) 6791–6795
6793
3. Experimental
3.1. General methods
Commercial spectral grade solvents were used for photo-
chemical experiments unless otherwise stated. For synthetic
use, tetrahydrofuran and diethyl ether were dried over the so-
dium ketyl of benzophenone; dichloromethane was dried
over calcium hydride; acetonitrile was distilled from P2O5.
Melting points were determined on a Fisher–Johns hot-stage
apparatus and uncorrected. Analytical TLC was performed
on 0.20 mm silica gel 60-F plates and visualized under UV
light and/or by staining with phosphomolybdic acid. Infra-
red spectra were recorded on a Perkin–Elmer 1710 Fourier
transform spectrometer. Low-resolution mass spectra were
obtained from a Kratos MS 50 instrument using electron
impact (EI) ionization at 70 eV. Elemental analyses were
1
performed on a Carlo Erba CHN Model 1106 analyzer. H
Figure 1. ORTEP presentation of X-ray crystal structure of (S)-(ꢁ)-1-p-
NMR spectra were obtained at 400 MHz on Bruker
AV-400 instruments. 13C NMR spectra were recorded at
100 MHz.
tolylethylammonium salt.
lab to synthesize natural products using this approach are
ongoing.
3.1.1. Methyl 2,2-diethyl-1-tetralone-6-carboxylate.
Methyl 1-tetralone-6-carboxylate (1.98 g, 9.7 mmol) pre-
pared from the methyl esterification of 1-tetralone-6-carbox-
ylic acid was dissolved in 75 mL of dry THF.13 To this stirred
solution, NaH (1.3 g, 60% dispersion in mineral oil,
32.5 mmol) was added at 0 ꢂC under nitrogen. After being
stirred for 10 min, ethyl iodide (2.32 mL) was added and
then the mixture was stirred at room temperature for 2
days. The reaction mixture was cooled to 0 ꢂC, quenched
with 1 N HCl, and extracted with diethyl ether. The ether ex-
tract was washed with saturated Na2S2O3 aqueous solution,
water, brine, dried over MgSO4, and filtered. The filtrate was
evaporated in vacuo to afford a crude product, which was
treated with CH2N2, and then purified by column chromato-
graphy on silica gel with pet ether–diethyl ether (20:1) to
Crystallographic data for the structures in this paper have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication nos. CCDC 631948
and 631949. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (fax: +44-(0)1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk).
1
give the ester 3 as an oil (1.16 g, 49% yield). H NMR
(400 MHz, CDCl3): d 8.06 (d, J¼8.0 Hz, 1H), 7.89 (d,
J¼8.3 Hz, 1H), 7.88 (s, 1H), 3.91 (s, 3H), 3.00 (t,
J¼6.3 Hz, 2H), 2.02 (t, J¼6.3 Hz, 2H), 1.67–1.69 (m, 2H),
1.59–1.61 (m, 2H), 0.83 (t, J¼7.5 Hz, 6H). 13C NMR
(100 MHz, CDCl3): d 201.5 (+), 166.5 (+), 143.0 (+),
135.2 (+), 133.5 (+), 130.1 (ꢁ), 128.0 (ꢁ), 127.9 (ꢁ), 52.4
(ꢁ), 48.0 (+), 29.9 (+), 26.2 (+)ꢃ2, 24.9 (+), 8.1 (ꢁ)ꢃ2.
IR (NaCl) nmax: 2969, 2940, 1727, 1684, 1437, 1280,
1097, 907, 752 cmꢁ1. LRMS (EI): 260 [M+], 245, 232
(100), 203, 189, 176, 148, 117, 103, 89, 77, 55. Anal.
Calcd for C16H20O3: C, 73.82; H, 7.74. Found: C, 73.48;
H, 7.88.
3.1.2. Irradiation of compound 3 in acetonitrile. The solu-
tion of 3 (70 mg, 0.27 mmol) in acetonitrile (30 mL) was
purged with N2 for 15 min and irradiated with 450 W me-
dium-pressure mercury lamp under N2 for 8 h. After irradi-
ation, the solvent was removed in vacuo and the residue was
purified by chromatography with pet ether–diethyl ether
(8:1) to give photoproduct 4 (46 mg, 66%) and the cleavage
product (6 mg, 10%) as colorless oils.
Photoproduct 4: 1H NMR (400 MHz, C6D6): d 8.10 (d,
J¼8.1 Hz, 1H), 8.00 (s, 1H), 7.62 (d, J¼8.1 Hz, 1H), 3.55
(s, 3H), 2.44–2.46 (m, 2H), 2.19–2.20 (m, 1H), 1.82–1.83
Figure 2. ORTEP presentation of mixed crystal containing 80% starting
material and 20% product (chiral auxiliary omitted for clarity).

6794
C. Yang et al. / Tetrahedron 63 (2007) 6791–6795
(m, 1H), 1.68–1.69 (m, 1H), 1.38–1.40 (m, 2H), 1.26–1.28
(m, 2H), 1.02–1.04 (m, 1H), 0.76 (t, J¼7.5 Hz, 3H). 13C
NMR (100 MHz, C6D6): d 166.9 (+), 148.7 (+), 137.0 (+),
129.9 (ꢁ), 128.9 (+), 126.8 (ꢁ)ꢃ2, 73.9 (+), 51.5 (ꢁ),
46.6 (+), 35.7 (+), 27.8 (+), 27.6 (+), 27.0 (+), 21.1 (+),
8.1 (ꢁ). IR (NaCl) nmax: 3480, 2944, 2356, 1718, 1703,
1437, 1289, 1113, 773 cmꢁ1. LRMS (EI): 260 [M+],
232(100), 217, 203, 177, 144, 115, 91, 77, 59. Anal. Calcd
for C16H20O3: C, 73.82; H, 7.74. Found: C, 73.33; H, 7.79.
(ꢁ)ꢃ2, 51.1 (ꢁ), 47.8 (+), 30.0 (+), 26.3 (+)ꢃ2, 24.8 (+),
19.7 (ꢁ), 7.3 (ꢁ)ꢃ2. IR (KBr) nmax: 3437, 2969, 2688,
LRMS (ESI): 368 [M++1], 269, 122, 105. Anal. Calcd for
C23H29NO3: C, 75.17; H, 7.95; N, 3.81. Found: C, 75.38;
H, 8.10; N, 3.63.
2176, 1647, 1620, 1526, 1386, 1221, 909, 762 cmꢁ1
.
3.2.2. (R)-(L)-1-Cyclohexylethylammonium salt. Mp
139–141 ꢂC (methanol). 1H NMR (400 MHz, CD3OD):
d 7.79 (d, J¼8.5 Hz, 1H), 7.66 (m, 2H), 2.93 (m, 1H), 2.90
(t, J¼6.3 Hz, 2H), 1.91 (t, J¼6.3 Hz, 2H), 1.62–1.65 (m,
5H), 1.58–1.60 (m, 2H), 1.48–1.50 (m, 2H), 1.36–1.38 (m,
1H), 1.11–1.12 (m, 3H), 1.10 (d, J¼6.8 Hz, 3H), 0.92–
0.93 (m, 2H), 0.71 (t, J¼7.5 Hz, 6H). 13C NMR (100 MHz,
CD3OD): d 204.0 (+), 174.3 (+), 144.4 (+), 143.6 (+),
134.2 (+), 130.6 (ꢁ), 128.1 (ꢁ)ꢃ2, 53.6 (ꢁ), 48.8 (+),
42.7 (ꢁ), 31.3 (+), 30.0 (+), 28.8 (+), 27.5 (+)ꢃ2, 27.3 (+),
27.1 (+), 27.0 (+), 26.0 (+), 16.0 (ꢁ), 8.5 (ꢁ)ꢃ2. IR (KBr)
nmax: 3437, 2932, 2674, 2161, 1672, 1629, 1520, 1373,
1219, 912, 777, 758 cmꢁ1. LRMS (ESI): 374 [M++1], 341,
280, 248, 128, 111, 69. Anal. Calcd for C23H35NO3: C,
73.96; H, 9.44; N, 3.75. Found: C, 74.26; H, 9.48; N, 3.68.
1
Cleavage product: H NMR (400 MHz, CDCl3): d 8.02 (d,
J¼8.5 Hz, 1H), 7.87–7.89 (m, 2H), 3.90 (s, 3H), 3.00–3.02
(m, 2H), 2.40–2.41 (m, 1H), 2.22–2.23 (m, 1H), 1.94–1.95
(m, 1H), 1.86–1.87 (m, 1H), 1.53–1.55 (m, 1H), 0.97 (t,
J¼7.5 Hz, 3H). 13C NMR (100 MHz, CDCl3): d 199.7 (+),
166.4 (+), 143.8 (+), 135.5 (+), 133.6 (+), 130.1 (ꢁ), 127.5
(ꢁ), 127.3 (ꢁ), 52.4 (ꢁ), 49.0 (ꢁ), 28.3 (+), 27.5 (+), 22.3
(+), 11.3 (ꢁ). IR (NaCl) nmax: 2954, 2873, 1725, 1687,
1437, 1282, 906, 746 cmꢁ1. LRMS (EI): 232 [M+], 217,
204 (100), 176, 145, 117, 89, 77, 63. Anal. Calcd for
C14H16O3: C, 72.39; H, 6.94. Found: C, 71.99; H, 7.08.
3.1.3. 2,2-Diethyl-1-tetralone-6-carboxylic acid. To a solu-
tion of keto-ester 3 (839 mg, 3.22 mmol) in THF (26 mL)
and H2O (13 mL) was added LiOH (1.2 g, 50 mmol). The
mixture was stirred at room temperature for 4 h and then
diethyl ether (40 mL) was added. The organic layer was
washed with water (3ꢃ25 mL) and the aqueous layers were
combined and acidified with concd HCl. The solution was
then extracted with diethyl ether (4ꢃ40 mL) and the com-
bined organic layer was washed with water (3ꢃ20 mL)
and dried over MgSO4. Removal of solvent in vacuo gave
a white solid, which was recrystallized from methanol to
afford keto-acid 5 as a white solid (778 mg, 98% yield),
3.2.3. (R)-(D)-b-Methylphenethylammonium salt. Mp
111–112 ꢂC (methanol). 1H NMR (400 MHz, CD3OD):
d 7.81 (d, J¼8.5 Hz, 1H), 7.68–7.69 (m, 2H), 7.22–7.23
(m, 2H), 7.16–7.18 (m, 3H), 2.99 (d, J¼7.0 Hz, 2H), 2.93–
2.95 (m, 1H), 2.90 (t, J¼6.3 Hz, 2H), 1.92 (t, J¼6.3 Hz,
2H), 1.59–1.60 (m, 2H), 1.46–1.48 (m, 2H), 1.20 (d,
J¼6.8 Hz, 3H), 0.72 (t, J¼7.3 Hz, 6H). 13C NMR
(100 MHz, CD3OD): d 203.9 (+), 174.2 (+), 144.4 (+),
143.4 (+)ꢃ2, 134.2 (+), 130.7 (ꢁ), 130.1 (ꢁ)ꢃ2, 128.5
(ꢁ), 128.2 (ꢁ)ꢃ2, 128.1 (ꢁ)ꢃ2, 49.1 (+), 46.9 (+), 39.8
(ꢁ), 31.2 (+), 27.5 (+)ꢃ2, 26.0 (+), 19.9 (ꢁ), 8.5 (ꢁ)ꢃ2.
IR (KBr) nmax: 3478, 2969, 2671, 2172, 1673, 1630, 1520,
1381, 1219, 909, 780, 762 cmꢁ1. LRMS (ESI): 382
[M++1], 349, 271, 136, 119, 91. Anal. Calcd for
C24H31NO3: C, 75.56; H, 8.19; N, 3.67. Found: C, 75.61;
H, 8.23; N, 3.59.
1
mp 168–169 ꢂC. H NMR (400 MHz, CDCl3): d 8.10 (d,
J¼8.0 Hz, 1H), 7.97 (d, J¼8.9 Hz, 1H), 7.96 (s, 1H), 3.02
(t, J¼6.3 Hz, 2H), 2.03 (t, J¼6.3 Hz, 2H), 1.68–1.70 (m,
2H), 1.58–1.60 (m, 2H), 0.83 (t, J¼7.4 Hz, 6H). 13C NMR
(100 MHz, CDCl3): d 201.5 (+), 171.5 (+), 143.1 (+),
135.8 (+), 132.6 (+), 130.7 (ꢁ), 128.1 (ꢁ), 127.9 (ꢁ), 48.0
(+), 29.8 (+), 26.2 (+)ꢃ2, 24.9 (+), 8.1 (ꢁ)ꢃ2. IR (KBr)
nmax: 3864, 2969, 2560, 1684, 1435, 1307, 1220, 907,
759 cmꢁ1. LRMS (ESI): 247 [M+ꢁ1], 214, 168, 142, 111,
83, 63. Anal. Calcd for C15H18O3: C, 73.15; H, 7.37. Found:
C, 73.29; H, 7.38.
3.2.4. (S)-(L)-1-p-Tolylethylammonium salt. Mp 159–
1
161 ꢂC (methanol). H NMR (400 MHz, CD3OD): d 7.75
(d, J¼8.5 Hz, 1H), 7.62–7.63 (m, 2H), 7.15 (d, J¼8.1 Hz,
2H), 7.04 (d, J¼8.0 Hz, 2H), 4.22 (q, J¼6.8 Hz, 1H), 2.84
(t, J¼6.3 Hz, 2H), 2.16 (s, 3H), 1.86 (t, J¼6.3 Hz, 2H),
1.52–1.53 (m, 2H), 1.43 (d, J¼6.9 Hz, 3H), 1.40–1.41 (m,
2H), 0.67 (t, J¼7.4 Hz, 6H). 13C NMR (100 MHz,
CD3OD): d 203.9 (+), 174.2 (+), 144.4 (+), 143.4 (+),
140.1 (+), 137.0 (+), 134.2 (+), 130.8 (ꢁ), 130.7 (ꢁ)ꢃ2,
128.1 (ꢁ)ꢃ2, 127.6 (ꢁ)ꢃ2, 52.0 (ꢁ), 48.8 (+), 31.2 (+),
27.5 (+)ꢃ2, 26.0 (+), 21.2 (ꢁ), 20.9 (ꢁ), 8.5 (ꢁ)ꢃ2. IR
(KBr) nmax: 3467, 2917, 2675, 2152, 1675, 1624, 1530,
1382, 1219, 912, 818, 756 cmꢁ1. LRMS (ESI): 382
[M++1], 359, 349, 271, 136, 119. Anal. Calcd for
C24H31NO3: C, 75.76; H, 8.19; N, 3.67. Found: C, 75.71;
H, 8.20; N, 3.56.
3.2. General procedure for synthesis of salts 6
To a solution of keto-acid 5 (80 mg, 32.5 mmol) in diethyl
ether (5 mL) was added an equivalent of optically pure
amine. Upon the addition, the precipitate formed immedi-
ately. The resulting suspension was filtered by suction to
give the salt, which was then recrystallized from methanol.
3.2.1. (S)-(L)-1-Phenylethylammonium and (R)-(D)-1-
phenylethylammonium salts. Mp 153–155 ꢂC (methanol).
1H NMR (400 MHz, CD3OD): d 7.87 (d, J¼8.6 Hz, 1H),
7.74 (m, 2H), 7.41–7.31 (m, 5H), 4.38 (q, J¼6.9 Hz, 1H),
2.97 (t, J¼6.3 Hz, 2H), 1.99 (t, J¼6.3 Hz, 2H), 1.65–1.66
(m, 2H), 1.56 (d, J¼6.8 Hz, 3H), 1.52–1.54 (m, 2H), 0.79
(t, J¼7.4 Hz, 6H). 13C NMR (100 MHz, CD3OD): d 202.8
(+), 173.0 (+), 143.3 (+), 142.2 (+), 138.9 (+), 133.1 (+),
129.5 (ꢁ), 129.0 (ꢁ)ꢃ2, 128.8 (ꢁ), 126.9 (ꢁ)ꢃ2, 126.4
3.3. Irradiation of (S)-(L)-1-phenylethylammonium
salts 6 in the solid state
The salt crystals (2–5 mg) were crushed between two Pyrex
microscope slides and sealed in a polyethylene bag under
a positive pressure of nitrogen. The sample was irradiated

C. Yang et al. / Tetrahedron 63 (2007) 6791–6795
6795
at ꢁ43 ꢂC or room temperature for 6.5–70 h from both sides
with a 450 W medium-pressure mercury lamp. After irradi-
ation, the salt crystals were suspended in an excess of
ethereal diazomethane solution and allowed to stand until
dissolution was complete. Ether and excess diazomethane
were removed in vacuo and the residue was taken up in meth-
ylene chloride and passed through a short plug of silica gel to
remove the chiral auxiliary. The residue was then submitted
to HPLC analysis to give the enantiomeric excesses and GC
analysis to give the conversions.
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W. Top. Curr. Chem. 2005, 254, 233; (c) Yang, C.; Xia, W.;
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Int. Ed. 2005, 5087; (d) Xia, W.; Scheffer, J. R.;
Botoshansky, M.; Kaftory, M. Org. Lett. 2005, 7, 1315; (e)
Xia, W.; Scheffer, J. R.; Brian, O. P. Cryst. Eng. Comm.
2005, 7, 728; (f) Xia, W.; Yang, C.; Scheffer, J. R.; Patrick,
B. O. Cryst. Eng. Comm. 2006, 8, 388.
7. The ratio of Norrish type II cyclization and cleavage product
is 6.5:1 based on GC analysis.
8. For a general review of the Norrish type II reaction, see:
Wagner, P.; Park, B.-S. Organic Photochemistry; Padwa, A.,
Ed.; Marcel Dekker: New York, NY, 1991; Vol. 11, Chapter 4.
9. Braga, D.; Chen, S.; Filson, H.; Maini, L.; Netherton, M. R.;
Patrick, B. O.; Scheffer, J. R.; Scott, C.; Xia, W. J. Am.
Chem. Soc. 2004, 126, 3511–3520.
Acknowledgements
We thank the Natural Sciences and Engineering Research
Council of Canada (NSERC) for support and Dr. Brian
O. Patrick for X-ray crystallographic analysis. C.Y. and
W.X. thank HIT for financial support (ATCZ98503334,
ATCZ98503335). C.Y. thanks the financial support from
the New Century Excellent Talent Program of Chinese
Ministry of Education.
10. Crystal data for (S)-(ꢁ)-1-p-tolylethylamine salt of keto-acid
5: C24H31N1O3, M¼381.50, orthorhombic, a¼6.7040(10),
3
˚
˚
b¼11.729(2), c¼27.072(6) A, V¼2128.7(7) A , T¼173 K,
space group P212121 (no. 19), Z¼4, m(Mo Ka)¼0.078 mmꢁ1
,
4012 reflections measured, 269 unique (Rint¼0.053), which
were used in all calculations. The final wR(F2) was 0.114 (all
data). Crystallographic data for the structures in this paper
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC 631948.
11. For a discussion of the dynamics of single crystal-to-single
crystal reactions, see: Kaupp, G. Curr. Opin. Solid State
Mater. Sci. 2002, 6, 131.
References and notes
1. (a) Wilson, B. J.; Wilson, C. H.; Hayes, A. W. Nature 1968,
220, 77; (b) Cole, R. J.; Dorner, J. W.; Lansden, J. A.; Cox,
R. H.; Pape, C.; Cunfer, B.; Nicholson, S. S.; Bedell, D. M.
J. Agric. Food Chem. 1977, 25, 1197; (c) Springer, J. P.;
Clardy, J. Tetrahedron Lett. 1980, 21, 231; (d) Gallagher,
R. T.; Clardy, J.; Wilson, B. J. Tetrahedron Lett. 1980, 21,
239; (e) Dorner, J. W.; Cole, R. J.; Cox, R. H.; Cunfer, B. M.
J. Agric. Food Chem. 1984, 32, 1069.
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419.
3. (a) Legrand, N.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron Lett.
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Tetrahedron 1995, 51, 3435.
12. Crystal data for (S)-(ꢁ)-1-p-tolylethylamine salt of keto-acid 5
irradiated to 20% conversion: C24H31N1O3, M¼381.50, ortho-
˚
rhombic, a¼6.7157(6), b¼11.7170(10), c¼26.856(3) A,
3
˚
V¼2113.2(4) A , T¼173 K, space group P212121 (no. 19),
Z¼4, m(Mo Ka)¼0.078 mmꢁ1, 4001 reflections measured,
273 unique (Rint¼0.072), which were used in all calculations.
The final wR(F2) was 0.172 (all data). Crystallographic data
for the structures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 631949.
13. Methyl 1-tetralone-6-carboxylate was prepared as following:
1-tetralone-6-carboxylic acid (2.0 g, 10.5 mmol) dissolved in
80 mL diethyl ether was added with ethereal diazomethane at
0 ꢂC until the solution turned to yellow. The resulted solution
was filtered on a silica gel column and rinsed with diethyl ether.
The solvent was then removed in vacuo to give a colorless oil as
methyl 1-tetralone-6-carboxylate, which was used in next steps
without further purifications.
4. (a) Rivkin, A.; Gonzalez-Lopez, T. F.; Nagashima, T.; Curran,
D. P. J. Org. Chem. 2004, 69, 3719; (b) Mander, L. N.; Wells,
A. P. Tetrahedron Lett. 1997, 38, 5709.
5. (a) Suginome, H.; Takeda, T.; Itoh, M.; Nakayama, Y.;
Kobayashi, K. Org. Bioorg. Chem. 1995, 1, 49; (b) Kakiuchi,
K.; Yamaguchi, B.; Kinugawa, M.; Ue, M. i.; Tobe, Y.;
Odaira, Y. J. Org. Chem. 1993, 58, 2797; (c) Suginome, H.;
Itoh, M.; Kobayashi, K. Chem. Lett. 1987, 8, 1527.