Organic Letters
Letter
catalyst for the photoredox C(sp3)−H functionalization.15 This
novel HAT catalyst have been successfully applied to the direct
arylation of allylic or benzylic C−H bonds. Herein, we disclose
the alkylarylsulfonamide as an efficient photoinduced HAT
catalyst for the alkylation of C(sp3)−H bonds adjacent to
heteroatoms. Not only alkenes but also alkyl bromides were
compatible alkylating source, providing an alternative platform
for C(sp3)−C(sp3) bond formations.
To validate the possibility of sulfamate as HAT catalyst, we
selected isopropyl tert-butylsulfamate (HAT 1) as the HAT
catalyst in cooperation with Ir-complex as photoredox catalyst
for the α-alkylation of tetrahydrofuran (THF) with benzyl
acrylate. Satisfactorily, the reaction proceeded smoothly in the
presence of 2 mol % of Ir[dF(CF3)ppy]2(dtbbpy)PF6, 20 mol
% of HAT 1, and 1.0 equiv of K3PO4·3H2O under 10W blue
LEDs irradiation, affording the desired product 3a in 60% yield
(Table 1, entry 1). As we know, the property of sulfamates and
3a in 6% yield, which displays the complementarity of our
HAT catalyst (entry 6). To our delight, 4CzIPN could
supplant the expensive Ir complex for this HAT reaction (entry
7). Other bases were also screened but led to diminished yields
(entries 8 and 9). In the absence of the HAT catalyst, only a
trace amount of product (<5% yield) was observed (entry 10).
Notably, a small amount of water is crucial for this reaction,
probably due to the improvement of the solubility of the base
(entry 11). Finally, control experiments revealed that photo-
catalyst, base, and light are all essential to this reaction (entries
12−14).
With the optimized conditions in hand, we investigated the
scope of electron-deficient alkenes with THF for this C(sp3)−
H alkylation protocol (Scheme 1). A wide range of α,β-
a
Scheme 1. Scope of Alkenes
a
Table 1. Optimization of the Reaction Conditions
entry
photocat.
HAT cat.
base
yield (%)
1
2
3
4
5
6
7
8
9
10
[Ir]PF6
[Ir]PF6
[Ir]PF6
[Ir]PF6
[Ir]PF6
[Ir]PF6
4CzIPN
4CzIPN
4CzIPN
4CzIPN
4CzIPN
HAT 1
HAT 2
HAT 3
HAT 4
HAT 5
HAT 6
HAT 3
HAT 3
HAT 3
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K2CO3
60
63
64
61
26
6
61
37
<5
<5
25
K3PO2(OtBu)3
K3PO4·3H2O
K3PO4
b
11
HAT 3
HAT 3
HAT 3
HAT 3
c
12
13
14
K3PO4
nr
nr
nr
c
4CzIPN
4CzIPN
d
c
K3PO4
a
Reaction conditions: 1a (1.0 mmol), 2a (0.2 mmol), photocatalyst
(2 mol %), HAT catalyst (20 mol %), base (0.2 mmol), and 0.1 mL of
distilled water in 2.0 mL of MeCN under the irradiation of 10 W blue
LEDs for 24 h under N2 at room temperature, [Ir]PF6 refers to
Ir[dF(CF3)ppy]2(dtbbpy)PF6. Yields of isolated product are shown.
No water was used. nr = no reaction. The reaction was carried out
without light irradiation.
a
Reaction conditions: 1a (1.0 mmol), 2 (0.2 mmol), 4CzIPN (2 mol
%), HAT 3 (20 mol %), K3PO4·3H2O (0.2 mmol), and 0.1 mL of
distilled water in 2.0 mL of MeCN under the irradiation of 10 W blue
LEDs for 24 h under N2 at room temperature. Yields of isolated
product are shown. Ratios of diastereoisomers were determined by 1H
NMR analysis. 1a (20.0 mmol) and 2a (4.0 mmol) were used. HAT
1 was used as the HAT catalyst. Ir(dF-CF3ppy)2dtbbpyPF6 was used
b
c
d
b
c
d
sulfamides as HAT catalyst would be largely affected by the
substituents on the nitrogen and sulfur atom. We then
examined a broad range of sulfamates and sulfonamides in
terms of the electron effect and steric effect (for details, see the
showed similar catalytic efficiency with HAT 1 for the
alkylation of THF, which is consistent with their calculated
BDE (N−H) values and transition-state barriers (entries 2 and
3). HAT 4 with slight lower BDE (N−H) value than HAT 3
was also competent in the reaction (entry 4). Replacement of
N-tert-butyl substituent with a less sterically hindered N-
isopropyl group resulted in a lower yield of 3a (26%, entry 5),
possibly because the bulkier t-Bu group significantly improves
the electronegativity of the nitrogen atom through an inductive
effect.16 It is noteworthy to mention that the reported
diarylsulfonamide HAT 6 only furnished the desired product
e
as the photocatalyst. 2.0 mmol of THF was used.
unsaturated esters were amenable to the standard reaction
conditions, producing the desired products 3a−3i in moderate
to good yields. Some important functional groups including
epoxide (3d), free alcohol (3e), and bromine (3i) were well-
tolerated. Notably, lactone (3j), cinnamic acid ester (3k), and
dimethyl fumarate (3l) were also suitable alkylating reagents
for this reaction. In addition, α,β-unsaturated esters, α,β-
unsaturated amides such as acrylamides (3m, 3n) and α-
methyl acrylamides (3o−3r) were engaged in the reaction,
yielding the alkylated products 3m−3r in 51−75% yields.
Other Michael acceptors such as α,β-unsaturated ketones (3s,
3t), sulfone (3u), and phosphonate (3v) were also compatible,
albeit with somewhat low yields. Remarkably, 2-vinylpyridine,
475
Org. Lett. 2021, 23, 474−479