Organic Letters
first evaluated with a typical organic photosensitizer and
analyzed with HPLC. After extensive condition screening, an
acridinium salt I was found to be the most powerful catalyst,
affording the desired product 3a under the irradiation of blue
light (6 W LED, 450 nm) (Table 1, entry 1). When 1 equiv of
a
Table 1. Catalyst Discovery and Reaction Optimization
variation from standard
conditions
conv.
b
yield
c
entry
catalyst
(%)
(%)
1
2
3
4
5
6
7
8
9
I
I
II
III
none
>95
89
82
95
90
<5
<5
>95
>95
>95
85
d
AcOH (1 equiv) added
none
none
69
35
79
60
<5
<5
64
80
91(88)
Na -Eosin Y none
none
I
I
I
I
2
none
performed in darkness
in pure CH Cl
in pure MeCN
Figure 1. The scope of alkenes. Unless otherwise stated, the reaction
2
2
was performed under N with an alkene 1 (0.2 mmol), CF SO Na
2
3
2
+
−
e
(63 mg, 0.4 mmol), 2 (96 mg, 0.4 mmol), and MesAcrMe ClO (1.6
4
1
0
2 and CF SO Na (2 equiv)
3
2
mg, 0.004 mmol) in MeCN/CH Cl (4:1, 4 mL) at 35−40 °C under
a
2
2
Unless otherwise stated, the reaction was performed under N with
a (35 μL, 0.2 mmol), CF SO Na (47 mg, 0.3 mmol), 2 (69 mg, 0.3
mmol), and a corresponding catalyst (0.004 mmol) in MeCN/
CH Cl (4:1, 4 mL) at 35 to 40 C under the irradiation of 6 W blue
LEDs. The conversion of 1a was determined by HPLC with an
internal standard. The yield of 3a was also measured by HPLC. A
nucleophilic adduct was observed. Isolated yield
2
1
3 2
̊
2
2
b
c
d
single diastereomer. Stilbene exhibited decent reactively to
provide product 4j in moderate diastereoselectivity. Non-
conjugated alkenes such as 1-octene, 1-dodecene, and
allylbenzene showed comparable reactivity to afford 4k−4m
in satisfactory yields. Next, a variety of functional-group-
containing substrates were evaluated with this catalytic
method. Starting with an O-TBS protected homoallylic
alcohol, 4n with a free hydroxyl group was obtained after
hydrolysis, while a benzoyl group remained intact (4a) with
the same procedure. The product of isopropyl pent-4-enoate
underwent a nucleophilic cyclization during deprotection,
providing 4o in 82% yield. Considering a carbon and a
nitrogen-centered radical were possibly involved in this
addition cascade, a few special substrates that might undergo
potential 1,5-H shift were studied. First, the reaction of but-3-
en-1-ylbenzene proceeded with good selectivity to generate 4p,
indicating 1,5-H shift from the benzylic position to N-radical is
not a concern during this process. Next, the selective
production of compound 4q demonstrated that 1,5-H shift
from benzylic C−H to a secondary carbon radical is not a
problem either. Nonconjugated internal alkenes were also
tolerated with this transformation, offering hydrazinium salts
4r and 4s in good yields. A 1,1-disubstituted and a
trisubstituted alkene also served as good substrates to afford
hydrazines on quaternary carbons (4t and 4u), respectively.
To demonstrate the potential synthetic applications, a few
derivatizations associated with the hydrazine group were
performed (Scheme 2). Hydrazinium salt 4b easily cyclized
with compound 5 to afford pyrazole 6, which highly resembles
e
AcOH was added as a proton source, the yield dropped to
some extent, accompanied by the detection of a nucleophilic
adduct (Table 1, entry 2). So, the N−H proton on 3a was
probably obtained from the NH Cl (aq.) during workup.
4
Other photosensitizers II, III, and Na -Eosin Y were also
2
reactive but not as effective (Table 1, entries 3−5).
Importantly, in the absence of a photosensitizer or without
light irradiation, no desired product was detected (Table 1,
entries 6, 7). Slightly lower yields were obtained when the
reaction was conducted in either pure CH Cl or MeCN
Table 1, entries 8−9). Eventually, 3a was isolated in excellent
yield when 2.0 equiv of each reagent were applied (Table 1,
entry 10).
With the optimized reaction conditions, several types of
alkenes were then inspected with this transition-metal-free
trifluoromethyl-hydrazination method. Because of the presence
of rotamers, the N-Boc protected hydrazines 3 show broad
peaks on NMR spectra at room temperature, which brought
difficulty to the structure identification. Therefore, compounds
were first purified through columns and then subjected for
deprotection (HCl in MeOH, 2 M) to afford hydrazinium salts
(Figure 1). First, a series of styrenes were smoothly
converted to the desired hydrazinium salts 4b−4g in good
yields after the two-step procedure. As a relatively electron-
deficient olefin, 2-vinylpyridine was also reactive under the
standard conditions, affording 4h in 71% yield. Similarly,
indene readily underwent the difunctionalization to give 4i as a
2
2
(
3
4
13
the core structure of ATZ-1993, but with a trifluoromethyl
B
Org. Lett. XXXX, XXX, XXX−XXX
Gong, Yuefa
