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Boc, Fmoc, and Troc groups all participated in the reaction,
only modest yields were achieved (Table 1, entries 16–18). In
the absence of either the photocatalyst or the light source, no
product was obtained (Table 1, entries 19 and 20).
Results and Discussion
We started our investigation by screening a number of organic
dyes for photocatalytic activities by using the reaction be-
tween benzyl hydroxycarbamate (1a) and a-methylstyrene
(2a) (Table 1). An 11 W household fluorescent lamp was used
as the visible light source. Of the dyes screened, RB showed
With the established conditions, the substrate scope of the
intermolecular ene reaction with 1a and styrene derivatives
was investigated (Table 2). A range of styrene derivatives 2a–f,
Table 1. Acylnitroso ene reaction between benzyl hydroxycarbamate (1)
and a-methylstyrene (2a).[a]
Table 2. Substrate scope studies for the acylnitroso ene reaction.[a]
Entry
R
t
[h]
Compound
Yield
[%][b]
Entry
Organic dye
Solvent
Additive
1
Yield
[%][b]
1
2
3
4
5
6
7
Ph (2a)
12
9
8
9
8
4a
4b
4c
4d
4e
4 f
78
81
50
76
83
82
33
p-MeC6H4 (2b)
p-MeOC6H4 (2c)
p-FC6H4 (2d)
p-ClC6H4 (2e)
p-CNC6H4 (2 f)
2-naphthyl (2g)
1
2
3
4
5
6
7
8
RB
eosin Y
fluorescein
rhodamine B
CH3CN
CH3CN
CH3OH
CH3CN
CH3CN
CH3CN
CH3OH
DMF
CH3CN/H2O (1:1)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
–
–
–
–
–
–
–
–
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1a
1a
35
31
22
10
8
10
30
methylene blue
4g
TPP
RB
RB
RB
RB
RB
RB
RB
RB
RB
RB
RB
RB
none
RB
5
[a] Reaction was performed by using 0.10 mmol of 1a and 0.30 mmol of
2 in 0.5 mL of CH3CN; [b] Isolated yield with respect to 1a.
24
25
25
44
60
58
77
71
78
45
53
50
0
9
–
10
11
12
13[c]
14[d]
15[e]
16[f]
17[f]
18[f]
19
20[g]
AcOH
pyridine
DMAP
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
–
with electron-withdrawing and electron-donating substituents,
underwent the desired reaction with 1a to provide the ene
products 4a–f in moderate to good yields (Table 2, entries 1–
6). However, if 2-(prop-1-en-2-yl)naphthalene (2g) was used,
a relatively low yield was obtained (Table 2, entry 7).
Next, the scope of the reaction was expanded to include
a series of aliphatic alkenes (Table 3). The reaction proceeded
smoothly to give allylic N-hydroxycarbamates in moderate to
good yields (Table 3, entries 1–9). Disubstituted trans-4-octene
gave better results than did monosubstituted 1-octene, possi-
bly owing to higher reactivity of the more electron-rich disub-
stituted olefins (Table 3, entries 1 and 2).[2a] Notably, the acylni-
troso enophile abstracts an allylic hydrogen from the geminal
alkyl group on the more substituted side of the alkene
(Table 3, entry 4).[13] Although singlet oxygen ene products
were detected if cyclohexene (Table 3, entry 3) was used, they
were formed in negligible amounts.
–
0
[a] Reaction was performed by using 0.10 mmol of 1 and 0.50 mmol of
2a in 0.5 mL of the solvent. RB=rose bengal; TPP=tetraphenylporphyr-
in; [b] Isolated yield with respect to 1; [c] Reaction was performed at
358C and completed after 10 h; [d] Reaction was performed at 458C and
completed after 7 h; [e] Reaction was performed at 358C by using
0.30 mmol of 2a and completed after 12 h; [f] Reaction was performed at
358C by using 0.30 mmol of 2a; [g] Reaction was performed in the dark.
the highest efficiency (Table 1, entry 1). Eosin Y gave a slightly
lower yield, whereas other dyes gave poor yields (Table 1, en-
tries 2–6). Solvent optimization showed that acetonitrile was
the best solvent for this photocatalytic reaction (Table 1, en-
tries 1, 7–9). As the reaction was sluggish, optimizations were
further performed by using additives (Table 1, entries 10–12).
An addition of 10 mol% pyridine resulted in higher reaction ef-
ficiency and improved yield (Table 1, entry 11). If the reaction
was run at an elevated temperature, 358C, the product yield
increased to 77% and the reaction was completed in 10 h
(Table 1, entry 13). However, if the temperature was increased
to 458C, the yield decreased slightly (Table 1, entry 14). The
amount of 2a was found to be lowered to 3 equiv compared
with that of 1a without any adverse effect on the yield
(Table 1, entry 15). Although hydroxylamines protected with
We next turned our focus to nitroso ene reactions with tiglic
acid derivatives (Table 3, entries 5–9). The products obtained
provide access to a,b-disubstituted amino acids, which have
few direct synthetic methodologies.[14] Poor yields were report-
ed previously by using tiglic acid derivatives as the ene sub-
strates because of the electron-deficient double bonds.[6] Mod-
erate-to-good yields were obtained with tiglic acid, tiglic
esters, and tiglic amide as the alkene partners under our reac-
tion conditions (Table 3, entries 5–8). The benzamide analogue
also underwent the ene reaction but cyclized in situ to form a-
methylene isoxazolidinone (Table 3, entry 9).
The reaction with 1-methyl-1-cyclohexene demonstrated a re-
markable preference for allylic hydrogen abstraction from the
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ChemCatChem 2013, 5, 235 – 240 236