ACS Catalysis
Research Article
a
RESULTS AND DISCUSSION
Table 1. Selected Optimization and Control Experiments
■
Transfer hydrogenation of olefins, a powerful alternative to
direct hydrogenation with molecular H2, circumvents the
requirement for pressurized, flammable gas, and specialized
equipment.19 The current transfer hydrogenation protocols
rely on oxygen sensitive transition metal hydride complexes,
which complicates catalyst handling and practicality.19b
Furthermore, unreliable chemoselectivity in the presence of
carbonyl, nitrile, benzylic ether, halogen, and other reducible
functional groups impedes the development of practical
methods for olefin transfer hydrogenation.20 We endeavored
to develop a formal transfer hydrogenation of olefins that
proceeds via a radical anion intermediate. In doing so, this
could provide a complementary method for chemoselective
reduction of alkenes, under mild reaction conditions, providing
direct access to valuable alkanes from diverse and commercially
available olefinic building blocks.
yield
b
entry
solvent
methanol
Ethanol
methanol
methanol
methanol
reductive quencher
[%]
1
2
3
4
5
6
7
8
Et3N
Et3N
14
7
1,2,2,6,6-pentamethylpiperidine
10
Bu3N
6
iPr2EtN
37
MeOH/H2O (9:1) iPr2EtN
55
c
MeOH/H2O (9:1) iPr2EtN/HCO2H (2.8 equiv)
MeOH/H2O (9:1) iPr2EtN/HCO2H (3.0 equiv)
MeOH/H2O (9:1) iPr2EtN/HCO2H (2.8 equiv)
MeOH/H2O (9:1)
82 (80)
79
d
9
ND
ND
ND
The design plan is shown in Figure 1a,b. Irradiation of
[Ir(ppy)2(dtb-bpy)]PF6 (Ir1) in the presence of triethylamine
leads to semisaturation of the dtb-bpy ligand, generating a
highly reducing species [Ir2]0 (Figure 1b). We propose that
the single electron transfer (SET) from [Ir2]0* to a conjugated
olefin such as 1,1-diphenylethylene (Eo = −2.25 V vs SCE)
generates a radical anion, that is immediately protonated to
give a stable benzylic radical. In the presence of the
triethylamine radical cation, an effective hydrogen atom
donor (BDE = 42 kcal mol−1),21 the radical undergoes a
hydrogen atom transfer (HAT) to yield the desired alkane.
Alternatively, a SET from [Ir2]0* to the radical intermediate
10
11
12
e
MeOH/H2O (9:1) iPr2EtN/HCO2H (2.8 equiv)
MeOH/H2O (9:1) bis(tetrabutylammonium)oxalate ND
a
General conditions: Olefin 1 (1.0 equiv), reductive quencher (2.2
equiv), solvent (0.1 M in substrate), sparged with N2 for 5 min; 24 h.
Yield determined by H NMR spectroscopy using sulfolene as an
internal standard. Isolated yield. Reaction performed without the
b
1
c
d
e
photocatalyst. Reaction performed with no irradiation. ND = Not
Detected.
control experiments (Table 1, entries 9−11) confirmed that no
reaction occurred in the absence of the photocatalyst, tertiary
amine, or visible light, consistent with the proposed reaction
mechanism. Furthermore, replacing iPr2EtN with bis-
(tetrabutylammonium)oxalate, which is known to reduce
[Ir1]+* without generating [Ir2]0,13 led to the full recovery
of the starting material and no trace of the reduced product 2
(Table 1, entry 12).
(E = −1.34 V vs SCE)22 generates a second carbanion,
red
1/2
which is quenched by a proton source. We hypothesized that
in the presence of a highly reducing [Ir2]0 catalyst and an
excess of triethylamine as the reductive quencher, the oxidation
pathway (Eo1/x2 = +0.23 V vs SCE) will be suppressed in favor of
either HAT or SET pathways to yield products of the formal
hydrogenation of alkenes (Figure 1c).
With the optimized reaction conditions established, we next
sought to evaluate the generality of the developed method by
examining the effect of variations in the 1,1-diphenylethylene
motif (Figure 2). The reaction was not sensitive to electronic
effects; high yields were obtained for both electron-with-
drawing (Figure 2, 4−10) and electron-donating substituents
(Figure 2, 12-17), which suggested that the highly reducing
tandem photoredox catalytic cycle of [Ir(ppy)2(dtb-bpy)]+
successfully suppressed the oxidation of the benzylic radical
and subsequent Markovnikov addition for most substrates.
Functionality at the ortho, meta, or para positions was well
tolerated. The reaction was compatible with fluorinated and
trifluoromethylated substituents (Figure 2, 4 and 5). Notably,
full chemoselectivity was observed in the presence of other
reducible functionalities including chloro, nitrile, ester, and
amide functional groups (Figure 2, 6−10 and 37).
Furthermore, reductive cleavage of the aromatic ether in 33a
was not observed (Figure 2, 33). The electron-poor
heterocyclic derivative was tolerated with the reduction of
the pyridyl derivative to give 11, proceeding in a good yield.
Given the prevalence of 1,1-diarylethanes in drug and
agrochemical products,19d,25 we synthesized two biologically
active derivatives; pesticide 1819d and antiviral (smallpox)
agent 1926 by reduction of the corresponding olefins. The
unoptimized yields in this reaction represent the first example
of direct access to these valuable targets from the
corresponding olefins in the absence of hydrogen gas.25c
We began our investigation into the photoredox-catalyzed
reduction of olefins using 1,1-diphenylethylene 1 as a model
substrate. Substrate 1 was combined with a catalyst and
triethylamine in methanol and irradiated with 80 W blue LEDs
(440 nm) for 24 h. The desired product 2 was detected in 14%
yield, with the full consumption of the starting material
1
observed by H NMR spectroscopic analysis of the crude
reaction mixture (Table 1, entry 1). Other alcoholic solvents
were less effective, likely due to poor solubility of the catalyst
and the substrate (Table 1, entry 2). On the other hand,
replacing triethylamine with diisopropylethylamine (iPr2EtN)
improved the yield to 37% (Table 1, entry 5), while addition of
water to the solvent system further increased the yield to 55%
(Table 1, entry 6). Analysis of the crude reaction mixture
revealed that yield was diminished by the formation of α-
details), likely promoted by electrostatic interaction between
the radical cation of iPr2EtN and the radical anion of the olefin
1.23 Consequently, formic acid was added to the reaction
i
mixture to convert Pr2EtN to the corresponding formate salt,
thus avoiding unproductive α-amino radical formation.24
Pleasingly, addition of a slight excess of formic acid relative
to iPr2EtN improved the yield to 82%, with no traces of the α-
amino adducts detected in the 1H NMR spectrum of the crude
reaction mixture (Table 1, entry 7). Higher loadings of formic
acid had little effect on the reaction (Table 1, entry 8). Finally,
5474
ACS Catal. 2021, 11, 5472−5480