Photochemical studies on acyclic alkyl aromatic ketones in the solid state: Asymmetric induction and increased chemoselectivity

Article abstract of DOI:10.1016/j.tet.2012.08.040

The acyclic alkyl aromatic ketones, 2-isobutyl-4-methyl-1-arylpentan-1-one derivatives were designed and synthesized for photochemical investigations. Irradiation of such compounds in acetonitrile solution led to the Yang cyclization and Norrish type II cleavage photoproducts with a ratio of 1:1, whereas the reaction conducted in the solid state using the ionic chiral auxiliary method led to only the Yang cyclization product with as high as 99% ee. Furthermore, the conformational transitions were first observed in the reaction.

Full text of DOI:10.1016/j.tet.2012.08.040

Tetrahedron 68 (2012) 8875e8879
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Photochemical studies on acyclic alkyl aromatic ketones in the solid state:
asymmetric induction and increased chemoselectivity
,
a,b,
Manling Ma a, Wei Feng a, Fang Guo a, Chao Yang a , Wujiong Xia
*
*
a The State Key Lab of Urban Water Resource and Environment & the Academy of Fundamental and Interdisciplinary Science, Harbin Institute of Technology, PO Box 3026, 2# Yikuang
Street, Harbin, Heilongjiang, PR China
b State Key Lab of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 June 2012
Received in revised form 3 August 2012
Accepted 14 August 2012
Available online 21 August 2012
The acyclic alkyl aromatic ketones, 2-isobutyl-4-methyl-1-arylpentan-1-one derivatives were designed
and synthesized for photochemical investigations. Irradiation of such compounds in acetonitrile solution
led to the Yang cyclization and Norrish type II cleavage photoproducts with a ratio of 1:1, whereas the
reaction conducted in the solid state using the ionic chiral auxiliary method led to only the Yang cy-
clization product with as high as 99% ee. Furthermore, the conformational transitions were first observed
in the reaction.
Keywords:
Acyclic
Ó 2012 Elsevier Ltd. All rights reserved.
Photochemical investigation
Yang cyclization
Norrish type II
Chiral auxiliary
1. Introduction
equilibrium mixture present in solution, and in such cases, the
ketones are unreactive in the solid state because they crystallize in
The solid-state reaction has attracted widespread interest and
attention owing to its several advantages compared to reactions
conducted in solution: increased reaction selectivity, the opportu-
nity to correlate chemical behavior with detailed structural in-
formation obtained through X-ray crystallography, simplicity in
process, and handling, and low environmental impact.1 Photo-
chemical reactions are particularly well suited for study in the solid
state because they can be conducted at ambient temperature or
below, where the crystals do not melt, and light is able to penetrate
deep within the crystal lattice.2 One aspect of organic solid-state
photochemistry that has received a great deal of attention re-
cently concerns its use in asymmetric synthesis.3 For example, in
the past two decades, many research efforts were focused on the
asymmetric studies on Norrish/Yang type II reactions and elegant
advances were achieved on the asymmetric induction through the
technique of zeolites,4 hosteguest assemblies,5 as well as ionic
chiral auxiliaries.6 However, the substrates employed in the re-
actions were mono- and/or polycyclic compounds. The asymmetric
study on acyclic substrates is still rare. This is because, for acyclic
ketones, the reactive conformer is often a minor component of the
thermodynamically more stable conformations that have the dis-
tance between carbonyl oxygen and -hydrogen more than
-hydrogen abstraction.7 Therefore, it
remains as a challenge for engineering acyclic ketones for solid-
state photochemical investigation. With our long-term research
on the organic photochemical reactions,8 we are intrigued to design
and synthesize 2-isobutyl-4-methyl-1-arylpentan-1-one de-
rivatives based upon the molecular mechanics calculations to
pursue such a goal through the ionic chiral auxiliary method.
The substrate, 2-isobutyl-4-methyl-1-arylpentan-1-one de-
g
ꢀ
2.8ꢀ0.2 A unfavorable for
g
rivative
5 chosen for investigation was synthesized from
4-methylpentanoic acid 1, which was treated with LDA and
1-bromo-2-methylpropane in THF to afford compound 2 in 82%
yield (Scheme 1). Reduction of compound 2 with LiAlH4 in THF led
to alcohol 3 in 95% yield, which was oxidized with pyridinium
chlorochromate (PCC) in CH2Cl2 and sequentially reacted with
Grignard reagent at low temperature to form the aromatic alcohol 4
in 56% yield. Oxidation of 4 with PCC in CH2Cl2 led to ketoeester 5.
Prior to the solid state studies, ketoeester 5 was photolyzed in
acetonitrile, which afforded a 1:1 ratio of photoproducts 6 (Yang
cyclization) and 7 (Norrish type II cleavage).9 The stereochemistry
i
of cyclobutanol 6 was established as cis (OH and Bu cis) by NOE
difference measurements; none of the trans cyclobutanol di-
astereomer could be detected by GC. For asymmetric synthesis,
* Corresponding authors. Tel.: þ86 451 86403193; fax: þ86 451 86403760; e-mail
addresses: xyyang@hit.edu.cn (C. Yang), xiawj@hit.edu.cn (W. Xia).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.040

8876
M. Ma et al. / Tetrahedron 68 (2012) 8875e8879
OH
Ar
i
ii
iii
COOH
CH2OH
COOH
1
2
3
4
O
O
iv
v
+
Ar
Ar
Ar
OH
CO2Me
Ar =
7
5
6
1
:
1
i
Scheme 1. (i) LDA, DMPU, THF, 1-bromo-2-methylpropane, ꢁ78 ꢂC; H2SO4 workup; 82% yield; (ii) LiAlH4, THF; 95% yield; (iii) PCC, CH2Cl2; p-IC6H4CO2CH3, PrMgBr, THF, ꢁ40 ꢂC;
56% yield (two steps); (iv) PCC, CH2Cl2; 96% yield; (v) hv, CH3CN.
ketoeester 5 was hydrolyzed to afford the corresponding keto-
eacid 8, and this compound was treated with a series of optically
pure amines to produce the corresponding ammonium carboxylate
salts 9 (Scheme 2). Such salts are required to crystallize in chiral
space groups (e.g., P212121) under the influence of amines, which
provide the asymmetric environment responsible for chiral in-
duction. Crystals of the salts 9 (2e5 mg) were crushed between two
microscope slides, and sealed in a polyethylene bag under nitrogen,
and irradiated with a 450 W medium mercury pressure lamp. After
irradiation, the photoproduct was treated with ethereal diazo-
methane to give the methyl esters, which were then analyzed by
chiral HPLC to obtain enantiomeric excess values and by GC to give
the conversions. The results are summarized in Table 1. Notably,
only the cyclization product 6 was obtained in the reaction. Such
a result represents one of the advantages of the solid-state reaction
that usually high chemo-/regioselectivity might be achieved due to
the molecules highly restricted in the crystals, in which the con-
formation is more favorable for the formation of one photoproduct
than the other.
presented in Fig. 1. A significant finding was that the carboxylate
anion of the (R)-(þ)-2-phenyl-1-propylamine salt of the keto acid 8
contained equal amounts of two independent conformers in the
crystal lattice when the crystal data was collected at ꢁ78 ꢂC (Fig.1i),
whereas at 10 ꢂC, the same crystal contained a single conforma-
tional enantiomer of the reactant (Fig. 1ii). Such a phenomenon was
first observed in this work and termed as conformational transitions.
In addition, the DSC analysis showed that the transition took place
between ꢁ25 ꢂC and ꢁ40 ꢂC. Unlike the reported conformational
enantiomerism, in which the two independent conformers are in
mirror-image relation in the crystal lattice usually led to the race-
mate or low ee,3d,10 the two conformers shown in Fig. 1(i) react in
the crystal to afford the same enantiomer of the cyclobutanol 6,
thereby leading to a high enantioselectivity.
As shown in Fig. 1, the enantioselectivity of the asymmetric
studies on salts 9 in the crystalline state was attributed to confor-
mational factors. Under the influence of the ionic chiral auxiliary,
the carboxylate reactant crystallizes in a homochiral conformation,
in which the carbonyl oxygen is closer to one g-hydrogen than to
O
i
iii
5
6
7
+
not observed
X
8
X = COOH
ii
9 X = COO- +NH3-R*
Scheme 2. (i) LiOH, THF/H2O (1:1); HCl; (ii) NH2-R*; (iii) hv, crystals; CH2N2 workup.
0
ꢀ
ꢀ
ꢀ
ꢀ
the other (e.g., in a, 3.102 A vs 4.607 A; in a , 3.062 A vs 3.266 A; in b,
Table 1
Asymmetric studies on the irradiation of salts 9 in the solid statea
ꢀ
ꢀ
3.029 A vs 3.364 A; Fig. 1). As a result, one of the g-hydrogens is
abstracted preferentially, affording a 1,4-biradical that leads to one
enantiomer of the final cyclobutanol photoproduct. Finally, a con-
trol experiment was conducted by irradiation of the salts 9 in
methanol, which led to racemic product 6 as well as the cleavage
product 7. This is typical and highlights the critical importance of
carrying out the reactions in the solid state and avoiding conditions
that could lead to crystal softening or melting. Therefore, the
enantioselectivity is the result of preorganization of the reactant in
a homochiral conformation favorable for the formation of a single
enantiomer of the product.
Amine
T
Time
(hr)
Conv
(%)b
ee
ad
(ꢂC)
(%)c
(S)-(ꢁ)-1-Phenyl ethylamine
rt
1
1
1
1
3
1
1
1
62
24
36
26
100
48
31
44
49
61
88
96
98
99
ꢁ
þ
ꢁ
ꢁ
ꢁ25
(S)-(ꢁ)-N-Methyl-1-phenyl ethylamine
(S)-(ꢁ)-1-p-Tolyl ethylamine
rt
ꢁ25
rt
ꢁ25
(R)-(þ)-2-Phenyl-1-propylamine
rt
75
53
ꢁ25
a
Samples were irradiated through Pyrex using
pressure mercury lamp.
a 450-W hanovia medium-
b
Conversion % based on GC.
ee % analyzed on chiral OD-H column with hexane:isopropanol¼99:1 as the
c
2. Conclusion
eluting solvent.
d
Sign of rotation at the sodium D-line.
In summary, the photochemical behavior of the acyclic alkyl
aromatic ketones was investigated in acetonitrile solution and in
the solid state. The solid-state reaction exhibited the high che-
moselectivity, in which only the cyclization product was formed.
Asymmetric studies through the utilization of ionic chiral auxil-
iary method led to as high as 99% ee. Furthermore, the
As can be seen in Table 1, the enantiomeric excess (ee) was
obtained as high as 99% in the solid state. To rationalize the results
observed, the X-ray single crystal structure of the (R)-(þ)-2-phenyl-
1-propylamine salt of the keto acid 8 was determined and

M. Ma et al. / Tetrahedron 68 (2012) 8875e8879
8877
Fig. 1. X-ray crystal structure of (R)-(þ)-2-phenyl-1-propylamine salt of the keto acid 8, (i) crystal data was collected at ꢁ78 ꢂC; (ii) crystal data was collected at 10 ꢂC.
phenomenon of conformational transitions was first observed in
the reaction. Remarkably, it should be pointed out that the formed
cyclobutanol photoproduct has the potential application in or-
ganic synthesis.11
Crystallographic data for the structures in this paper have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication nos. CCDC 798458, 798459. Copies of
the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK, (fax: þ44-(0)1223-336033 or
e-mail:deposit@ccdc.cam.ac.uk).
methylpentanal was used for next step without purification
(GC detected the purity is 98%, which is pure enough for next step).
To the solution of methyl p-iodobenzoate (2.5 g, 9.5 mmol) in
50 mL of dried THF precooled at ꢁ40 ꢂC was added isopropyl
magnesium chloride (2 M, 4.75 mL), dropwise. After addition, the
mixture was stirred for 1 h at this temperature. To this solution,
2-isobutyl-4-methylpentanal was dissolved in dry THF (10 mL) and
added slowly. The solution was stirred at ꢁ40 ꢂC for 4 h. Saturated
ammonium chloride solution (30 mL) was added quickly and the
solution was extracted with diethyl ether (3ꢃ50 mL), and the
combined organic layer was washed with saturated brine solution
(2ꢃ30 mL). The solvent was removed in vacuo after being dried
over magnesium sulfate, and the residue was purified by chroma-
tography (20% pet ether/diethyl ether) to give the alcohol 4 as an oil
3. Experimental
(1.55 g, 56% yield). 1H NMR (400 MHz, CDCl3):
d
8.02 (d, J¼8.0 Hz,
3.1. General methods
2H), 7.40 (d, J¼8.0 Hz, 2H), 4.88 (d, J¼3.5 Hz, 1H), 3.93 (s, 3H), 1.84
(m, 1H), 1.69 (m, 1H), 1.50 (m, 1H), 1.40 (m, 1H), 1.10 (m, 1H), 1.06 (m,
2H), 0.94 (d, J¼6.3 Hz, 3H), 0.92 (d, J¼6.3 Hz, 3H), 0.82 (d, J¼6.5 Hz,
Commercial spectral grade solvents were used for photochem-
ical experiments unless otherwise stated. Infrared spectra were
recorded on a PerkineElmer 1710 Fourier transform spectrometer.
Melting points were determined on a FishereJohns apparatus.
Low-resolution mass spectra were obtained from a Kratos MS 50
instrument using electron impact (EI) ionization at 70 eV. 1H NMR
spectra were obtained at 400 MHz on Bruker AV-400 instrument.
13C NMR spectra were recorded at 100 MHz.
3H), 0.65 (d, J¼6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3):
d
167.1 (þ),
149.3 (þ), 129.3 (ꢁ), 128.7 (þ), 126.0 (ꢁ), 75.1 (ꢁ), 52.0 (ꢁ), 40.4 (þ),
40.3 (ꢁ), 38.0 (þ), 25.4(ꢁ), 25.2(ꢁ), 23.5(ꢁ), 23.3(ꢁ), 22.5(ꢁ),
21.9(ꢁ). IR (neat) nmax: 3477, 2955, 1726, 1708, 1611, 1282, 1115, 869,
759, 712 cmꢁ1. LRMS (EI): 292 [Mþ], 261, 245, 166, 151, 134, 106, 91,
77, 57. HRMS (EI) for C14H16O3: calcd 232.1099; found 232.1095.
3.1.2. Methyl 4-(2-isobutyl-4-methylpentanoyl)benzoate 5. To a so-
lution of alcohol 4 (1.0 g, 3.42 mmol) in 30 mL of anhydrous
methylene chloride were added PCC (1.10 g, 5.13 mmol) and Celite
(2 g). The mixture was stirred at room temperature overnight and
diethyl ether (20 mL) was added. The solution was then filtered
through a silica gel column and rinsed with diethyl ether. The
solvent was removed in vacuo and the residue purified by column
chromatography (10% pet ether/diethyl ether) to give ketoeester 5
3.1.1. Methyl
4-(1-hydroxy-2-isobutyl-4-methylpentyl)benzoate
(4). 2-Isobutyl-4-methylpentan-1-ol (1.5 g, 9.5 mmol) prepared
from the reduction of 2-isobutyl-4-methylpentanoic acid was dis-
solved in 120 mL of methylene chloride. To this solution, PCC (3.08 g,
14.3 mmol) and Celite (6 g) ground homogeneously in mortar were
added. The mixture was stirred at room temperature overnight,
filtered with silica gel column, and rinsed with diethyl ether. The
solvent was then removed in vacuo, and the residue 2-isobutyl-4-

8878
M. Ma et al. / Tetrahedron 68 (2012) 8875e8879
as a colorless crystal (953 mg, 96% yield). Mp 56e58 ꢂC. 1H NMR
(400 MHz, CDCl3):
(q, J¼6.9 Hz,1H), 3.59 (m,1H),1.54 (m, 2H),1.51 (d, J¼6.9 Hz, 3H),1.43
d
8.17 (d, J¼8.4 Hz, 2H), 8.04 (d, J¼8.4 Hz, 2H),
(m, 2H),1.19 (m, 2H), 0.79 (d, J¼6.5 Hz, 6H), 0.78 (d, J¼6.5 Hz, 6H).13
C
3.98 (s, 3H), 3.62 (m, 1H), 1.74 (m, 2H), 1.61 (m, 2H), 1.37 (m, 2H),
NMR (100 MHz, CD3OD):
d
206.8 (þ), 173.9 (þ), 143.5 (þ), 140.1 (þ),
0.92 (d, J¼6.4, 6H), 0.89 (d, J¼6.4 Hz, 6H). 13C NMR (100 MHz,
140.0 (þ),130.5 (ꢁ),130.2 (ꢁ),130.1 (ꢁ),128.8 (ꢁ),127.6 (ꢁ), 52.3 (ꢁ),
CDCl3):
d
204.3 (þ), 166.2 (þ), 140.8 (þ), 133.6 (þ), 129.9 (ꢁ), 128.0
43.5 (ꢁ), 43.3 (þ), 27.4 (ꢁ), 23.3 (ꢁ), 23.1 (ꢁ), 20.9 (ꢁ). IR (KBr) nmax
:
(ꢁ), 52.4 (ꢁ), 42.7 (ꢁ), 41.7 (þ), 26.1 (ꢁ), 22.8 (ꢁ), 22.7 (ꢁ). IR (KBr)
nmax: 2954, 2868, 1724, 1670, 1280, 1108, 828, 785, 730 cmꢁ1. LRMS
(EI): 290 [Mþ], 275, 259, 234, 191, 163, 135, 104, 76, 55. Anal. calcd
for C18H26O3: C, 74.45; H, 9.02. Found: C, 74.78; H, 9.17.
3420, 2955, 2553, 2201, 1673, 1635, 1582, 1391, 793, 732, 700 cmꢁ1
.
LRMS (ESI): 398 [Mþþ1], 122, 105. Anal. calcd for C25H35NO3: C,
75.53; H, 8.87; N, 3.52. Found: C, 75.90; H, 8.78; N, 3.55.
3.2.2. (S)-(ꢁ)-N-Methyl-1-phenylethylamine salt of ketoeacid 8. Mp
3.1.3. Irradiation of compound 5 in acetonitrile. The solution of 5
(60 mg, 0.21 mmol) in acetonitrile (20 mL) was purged with N2 for
15 min and irradiated with 450 W medium mercury pressure lamp
under N2 for 1.0 h. After irradiation, the solvent was removed in
vacuo and the residue was purified by chromatography (10% pet
ether/diethyl ether) to give photoproduct 6 (25 mg, 43%) and 7
(24 mg, 41%).
83e85 ꢂC (Methanol).1H NMR (400 MHz, CD3OD):
d
7.93 (d, J¼8.5 Hz,
2H), 7.86 (d, J¼8.5 Hz, 2H), 7.33 (m, 5H), 4.16 (q, J¼6.9 Hz,1H), 3.59 (m,
1H), 2.43 (s, 3H),1.54 (d, J¼6.9 Hz, 3H),1.52 (m, 2H),1.43 (m, 2H),1.20
(m, 2H), 0.79 (d, J¼6.6 Hz, 6H), 0.78 (d, J¼6.5 Hz, 6H). 13C NMR
(100 MHz, CD3OD):
d
206.8 (þ), 173.9 (þ), 143.3 (þ), 140.0 (þ), 138.1
(þ),130.6 (ꢁ),130.5 (ꢁ),130.4 (ꢁ),128.8 (ꢁ),128.6 (ꢁ), 60.5 (ꢁ), 43.5
(ꢁ), 43.3 (þ), 31.6 (ꢁ), 27.4 (ꢁ), 23.3 (ꢁ), 23.1 (ꢁ), 19.4 (ꢁ). IR (KBr)
nmax: 2954, 2777, 2378, 2129, 1672, 1552, 1382, 877, 795, 735,
700 cmꢁ1. LRMS (ESI): 412 [Mþþ1], 136, 105, 79. Anal. calcd for
C26H37NO3: C, 75.87; H, 9.06; N, 3.40. Found: C, 76.00; H, 9.24; N, 3.50.
Photoproduct 6. 1H NMR (400 MHz, C6D6):
d
8.15 (d, J¼6.7 Hz,
2H), 7.28 (d, J¼6.7 Hz, 2H), 3.52 (s, 3H), 2.83 (m, 1H), 1.66 (m, 1H),
1.45 (m, 1H), 1.27 (m, 1H), 1.20 (s, 3H), 1.14 (m, 1H), 0.88 (d, J¼6.6 Hz,
3H), 0.85 (d, J¼6.6 Hz, 3H), 0.66 (s, 3H). 13C NMR (100 MHz, C6D6):
d
166.6 (þ), 149.5 (þ), 129.8 (ꢁ), 129.5 (ꢁ), 126.4 (ꢁ), 81.6 (þ), 51.6
3.2.3. (S)-(ꢁ)-1-p-Tolylethylamine salt of ketoeacid 8. Mp
(ꢁ), 41.5 (þ), 38.0 (þ), 37.8 (þ), 35.1 (ꢁ), 26.6 (ꢁ), 26.3 (ꢁ), 23.5 (ꢁ),
23.0 (ꢁ), 22.3 (ꢁ). IR (KBr) nmax: 3502, 2954, 2868, 1724, 1711, 1610,
1280, 1112, 851, 772, 725 cmꢁ1. LRMS (EI): 290 [Mþ], 275, 259, 234,
219, 206, 191, 178, 159, 131. HRMS (EI) for C18H26O3: calcd 290.1882;
found 290.1885.
162e164 ꢂC (Methanol). 1H NMR (400 MHz, CD3OD):
d 7.89 (d,
J¼8.5 Hz, 2H), 7.83 (d, J¼8.5 Hz, 2H), 7.19 (d, J¼8.0 Hz, 2H), 7.10 (d,
J¼8.0 Hz, 2H), 4.26 (q, J¼6.9 Hz, 1H), 3.56 (m, 1H), 2.20 (s, 3H), 1.51
(m, 2H), 1.47 (d, J¼6.9 Hz, 3H), 1.41 (m, 2H), 1.18 (m, 2H), 0.76 (d,
J¼6.5 Hz, 6H), 0.75 (d, J¼6.5 Hz, 6H). 13C NMR (100 MHz, CD3OD):
Photoproduct 7. 1H NMR (400 MHz, CDCl3):
d
8.17 (d, J¼8.4 Hz,
d
206.7 (þ), 174.0 (þ), 143.5 (þ), 140.1 (þ), 139.9 (þ), 136.9 (þ), 130.8
2H), 8.04 (d, J¼8.4 Hz, 2H), 3.97 (s, 3H), 3.60 (m, 2H),1.74 (m, 2H),1.61
(ꢁ), 130.5 (ꢁ), 128.8 (ꢁ), 127.6 (ꢁ), 52.0 (ꢁ), 43.5 (ꢁ), 43.3 (þ), 27.4
(ꢁ), 23.3 (ꢁ), 23.1 (ꢁ), 21.2 (ꢁ), 20.8 (ꢁ). IR (KBr) nmax: 2957, 2869,
2546, 2187, 1674, 1648, 1581, 1392, 1245, 816, 792, 727 cmꢁ1. LRMS
(ESI): 412 [Mþþ1], 349, 312, 271,136,119. Anal. calcd for C26H37NO3:
C, 75.87; H, 9.06; N, 3.40. Found: C, 76.00; H, 9.20; N, 3.46.
(m, 1H), 0.92 (d, J¼6.4, 6H). 13C NMR (100 MHz, CDCl3):
202.3 (þ),
d
166.2 (þ),140.6 (þ),133.4 (þ),129.8 (ꢁ),128.1 (ꢁ), 52.2 (ꢁ), 42.3 (ꢁ),
40.9 (þ), 26.0 (ꢁ), 22.8 (ꢁ). IR (KBr) nmax: 2956, 2864, 1724, 1670,
1270, 824, 780, 730 cmꢁ1. LRMS (EI): 234 [Mþ], 219, 203,191,163,135,
104, 55. HRMS (EI) for C14H18O3: calcd 234.1256; found 234.1260.
3.2.4. (R)-(þ)-2-Phenyl-1-propylamine salt of ketoeacid 8. Mp
3.1.4. 4-(2-Isobutyl-4-methylpentanoyl)benzoic acid 8. To a solution
of ketoeester 5 (950 mg, 3.28 mmol) in THF (30 mL) and H2O
(15 mL) was added LiOH (1.5 g, 62 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 combined 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 ketoeacid 8 as
a white solid (896 mg, 99% yield). Mp 95e96 ꢂC. 1H NMR (400 MHz,
115e116 ꢂC (Methanol). 1H NMR (400 MHz, CD3OD):
d 7.89 (d,
J¼8.5 Hz, 2H), 7.82 (d, J¼8.5 Hz, 2H), 7.18 (m, 2H), 7.12 (m, 3H), 3.55
(m, 1H), 2.98 (d, J¼7.0 Hz, 2H), 2.92 (m, 1H), 1.49 (m, 2H), 1.39 (m,
2H), 1.18 (d, J¼6.8 Hz, 3H), 1.15 (m, 2H), 0.75 (d, J¼6.5 Hz, 6H), 0.73
(d, J¼6.5 Hz, 6H). 13C NMR (100 MHz, CD3OD):
206.8 (þ), 174.0 (þ),
d
143.5 (þ), 143.4 (þ), 140.0 (þ), 130.5 (ꢁ), 130.1 (ꢁ), 128.8 (ꢁ),
128.5(ꢁ), 128.2 (ꢁ), 46.9 (þ), 43.6 (ꢁ), 43.5 (þ), 39.8 (ꢁ), 27.4 (ꢁ),
23.3 (ꢁ), 23.1 (ꢁ), 19.9 (ꢁ). IR (KBr) nmax: 2961, 2698, 2198, 1674,
1582, 1532, 1385, 1209, 836, 794, 759, 732 cmꢁ1. LRMS (ESI): 412
[Mþþ1],136, 105, 79. Anal. calcd for C26H37NO3: C, 75.87; H, 9.06; N,
3.40. Found: C, 76.10; H, 9.30; N, 3.45.
CDCl3):
d
8.25 (d, J¼8.4 Hz, 2H), 8.06 (d, J¼8.4 Hz, 2H), 3.63 (m, 1H),
1.73 (m, 2H), 1.61 (m, 2H), 1.38 (m, 2H), 0.94 (d, J¼6.8 Hz, 6H), 0.90
3.3. General procedure for irradiation of salts 9 in the solid
state
(d, J¼6.8 Hz, 6H). 13C NMR (100 MHz, CDCl3):
204.3 (þ), 170.4 (þ),
d
141.6 (þ), 132.6 (þ), 130.6 (ꢁ), 128.1 (ꢁ), 42.6 (ꢁ), 41.7 (þ), 26.2 (ꢁ),
22.9 (ꢁ), 22.7(ꢁ). IR (KBr) nmax: 3319, 3068, 2956, 2672, 2552, 1683,
The salt crystals (2e5 mg) were crushed between two Pyrex
microscope slides and sealed in a polyethylene bag under a positive
pressure of nitrogen. The sample was irradiated from both sides
with a 450 W medium pressure mercury lamp. After irradiation, 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 methylene 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.
1290, 872, 782, 725 cmꢁ1. LRMS (ESI, infusion @ 10
mL/min in MeOH
ꢁve mode): 275.2 [Mþꢁ1]. Anal. calcd for C17H24O3: C, 73.88; H,
8.75. Found: C, 73.89; H, 8.45.
3.2. General procedure for synthesis of salts 9
To the solution of ketoeacid 8 (100 mg, 0.36 mmol) in diethyl
ether (5 mL) was added an equivalent of optically pure amine. Upon
the addition, the precipitate formed immediately. The resulted
suspension was filtered by suction to give the salt, which was then
recrystallized from methanol.
Acknowledgements
3.2.1. (S)-(ꢁ)-1-Phenylethylamine salt of ketoeacid 8. Mp
146e148 ꢂC (Methanol). 1H NMR (400 MHz, CD3OD):
d
7.92 (d,
We are grateful for the financial supports from China NSFC (Nos.
J¼8.5 Hz, 2H), 7.86 (d, J¼8.5 Hz, 2H), 7.33 (m, 2H), 7.28 (m, 3H), 4.33
21002018 and 21072038), the Fundamental Research Funds for the

M. Ma et al. / Tetrahedron 68 (2012) 8875e8879
8879
4. (a) Joy, A.; Ramamurthy, V. Chem.dEur. J. 2000, 6, 1287; (b) Sivaguru, J.;
Natarajan, A.; Kaanu-malle, L. S.; Shailaja, J.; Uppili, S.; Joy, A.; Ramamurthy, V.
Acc. Chem. Res. 2003, 36, 509.
Central Universities (No. HIT.BRET2.2010001), and ZJSTP (No.
2011C23116).
5. (a) Toda, F.; Tanaka, K.; Miyamoto, H. In Molecular and Supramolecular Photo-
chemistry; Ramamurthy, V., Schanze, K. S., Eds.; Marcel Dekker: New York, NY,
2001; Vol. 8, Chapter 6; (b) Tanaka, K.; Toda, F. In Organic Solid-state Reactions;
Toda, F., Ed.; Kluwer: 2002; p 109.
References and notes
6. (a) Gamlin, J. N.; Jones, R.; Leibovitch, M.; Patrick, B.; Scheffer, J. R.; Trotter, J.
Acc. Chem. Res. 1996, 29, 203; (b) Yang, C.; Xia, W. Chem.dAsian. J. 2009, 4, 1774.
7. Scheffer, J. R.; Scott, C. In CRC Handbook of Organic Photochemistry and Photo-
biology, 2nd ed.; Horspool, W. M., Lenci, F., Eds.; CRC: Boca Raton, FL, 2004,
Chapter 54.
8. (a) Xia, W.; Shao, Y.; Gui, W.; Yang, C. Chem. Commun. 2011, 11098; (b) Shao, Y.;
Yang, C.; Gui, W.; Liu, Y.; Xia, W. Chem. Commun. 2012, 3560.
9. Cyclobutanol formation in the Norrish type II reaction, now referred to as Yang
photocyclization, was first reported by Yang, N. C.; Yang, D. H. J. Am. Chem. Soc.
1958, 80, 2913.
1. (a) Photochemistry in Organized and Constrained Media; Ramamurthy, V., Ed.;
VCH: New York, NY, 1991; (b) Molecular and Supramolecular Photochemistry;
Ramamurthy, V., Schanze, K. S., Eds.; Marcel Dekker: New York, NY, 2000; Vol.
5, Chapter 6; (c) Scheffer, J. R.; Xia, W. Top. Curr. Chem. 2005, 254, 233.
2. (a) Everitt, S. R. L.; Inoue, Y. In Molecular and Supramolecular Photochemistry;
Ramamurthy, V., Schanze, K. S., Eds.; Marcel Dekker: New York, NY, 1999; Vol. 3,
p 71; (b) Pete, J. P. Adv. Photochem. 1996, 21, 135; (c) Inoue, Y. Chem. Rev. 1992,
92, 471; (d) Buschmann, H.; Scharf, H. D.; Hoffmann, N.; Esser, P. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 477; (e) Rau, H. Chem. Rev. 1983, 83, 535.
3. (a) Scheffer, J. R. Can. J. Chem. 2001, 79, 349; (b) Xia, W.; Yang, C.; Patrick, B. O.;
Scheffer, J. R.; Scott, C. J. Am. Chem. Soc. 2005, 127, 2725; (c) Yang, C.; Xia, W.;
Scheffer, J. R.; Botoshansky, M.; Kaftory, M. Angew. Chem., Int. Ed. 2005, 44,
5087; (d) Xia, W.; Scheffer, J. R.; Botoshansky, M.; Kaftory, M. Org. Lett. 2005, 7,
1315; (e) Yang, C.; Xia, W.; Scheffer, J. R. Tetrahedron 2007, 63, 6791; (f) Zhao, G.;
Yang, C.; Chen, Q.; Jin, J.; Zhang, X.; Zhao, L.; Xia, W. Tetrahedron 2009, 65, 9952.
10. The conformational enantiomerism was previously reported in (a) Cheung, E.;
Kang, T.; Netherton, M. R.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc. 2000, 122,
11753; (b) Natarajan, A.; Wang, K.; Ramamurthy, V.; Scheffer, J. R.; Patrick, B.
Org. Lett. 2002, 4, 1443.
11. Ziadi, A.; Martin, R. Org. Lett. 2012, 14, 1266.