Light-enabled metal-free pinacol coupling by hydrazine

Article abstract of DOI:10.1039/c9sc03737c

Efficient carbon-carbon bond formation is of great importance in modern organic synthetic chemistry. The pinacol coupling discovered over a century ago is still one of the most efficient coupling reactions to build the C-C bond in one step. However, traditional pinacol coupling often requires over-stoichiometric amounts of active metals as reductants, causing long-lasting metal waste issues and sustainability concerns. A great scientific challenge is to design a metal-free approach to the pinacol coupling reaction. Herein, we describe a light-driven pinacol coupling protocol without use of any metals, but with N₂H₄, used as a clean non-metallic hydrogen-atom-transfer (HAT) reductant. In this transformation, only traceless non-toxic N₂ and H₂ gases were produced as by-products with a relatively broad aromatic ketone scope and good functional group tolerance. A combined experimental and computational investigation of the mechanism suggests that this novel pinacol coupling reaction proceeds via a HAT process between photo-excited ketone and N₂H₄, instead of the common single-electron-transfer (SET) process for metal reductants.

Full text of DOI:10.1039/c9sc03737c

Chemical
Science
View Article Online
View Journal
EDGE ARTICLE
Light-enabled metal-free pinacol coupling by
hydrazine†
Cite this: DOI: 10.1039/c9sc03737c
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
Zihang Qiu, ‡ Hanh D. M. Pham,‡ Jianbin Li,
Chen-Chen Li,
Durbis J. Castillo-
*
*
Pazos,
Rustam Z. Khaliullin
and Chao-Jun Li
Efficient carbon–carbon bond formation is of great importance in modern organic synthetic chemistry. The
pinacol coupling discovered over a century ago is still one of the most efficient coupling reactions to build
the C–C bond in one step. However, traditional pinacol coupling often requires over-stoichiometric
amounts of active metals as reductants, causing long-lasting metal waste issues and sustainability
concerns. A great scientific challenge is to design a metal-free approach to the pinacol coupling
reaction. Herein, we describe a light-driven pinacol coupling protocol without use of any metals, but
with N2H4, used as a clean non-metallic hydrogen-atom-transfer (HAT) reductant. In this transformation,
only traceless non-toxic N2 and H2 gases were produced as by-products with a relatively broad aromatic
ketone scope and good functional group tolerance. A combined experimental and computational
investigation of the mechanism suggests that this novel pinacol coupling reaction proceeds via a HAT
process between photo-excited ketone and N2H4, instead of the common single-electron-transfer (SET)
process for metal reductants.
Received 29th July 2019
Accepted 6th October 2019
DOI: 10.1039/c9sc03737c
rsc.li/chemical-science
metal are typically problematic, especially in large scale reac-
tions, generating large amounts of metal waste and causing
environmental concerns.4
1. Introduction
Development of economical and efficient methods for creating
the carbon–carbon bond is of paramount importance in
modern synthetic chemistry.1 In this regard, the pinacol
coupling, though historically discovered over a century ago, is
still one of the most efficient reactions to introduce the carbon–
carbon bond in one step.2 Traditionally, more than the stoi-
chiometric amount of metal reductants (Mg, Al, Zn, Mn, etc.) is
required to realize the single-electron-transfer (SET) process
from the metal to the carbonyl group and to generate the ketyl
radical as the key intermediate to form the pinacol product with
the help of various Brønsted or Lewis acid additives (H+, SiR3Cl,
TiCl4, ZnCl2, AlCl3, etc.). The acids are vital to coordinate with
the carbonyl group to lower the SET barrier and to increase the
pinacol product selectivity over the simple alcohol product (the
two-electron reduced form of ketone) (Scheme 1a). Although it
is an apparently straight-forward process, carefully choosing the
acid additives is always needed, otherwise it results in poor
reactivity and selectivity towards pinacol.3 Besides, pre-activa-
tion of the excess amount of metals is oen needed to remove
the oxide from the metal surface and efficiently utilize them as
reductants. Furthermore, the work-up processes of the excess
To partially solve the problems of excessive metal mentioned
above, pioneering work by Rueping et al. applied [Ir] based
photo-redox catalysts to generate the key ketyl radicals from
ketones via SET with tertiary amines as sacricial reductants
instead of metals and to realize the pinacol coupling (Scheme
1a).5 Although successful, the method still required precious
noble metal [Ir] based photo-redox catalysts. Therefore, we were
pondering the possibility of designing a pinacol coupling
Department of Chemistry, FQRNT Centre for Green Chemistry and Catalysis, McGill
University, 801 Sherbrooke St. W., Montreal, Quebec H3A 0B8, Canada. E-mail:
rustam.khaliullin@mcgill.ca; cj.li@mcgill.ca
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c9sc03737c
‡ These authors contributed equally to this work.
Scheme 1 Previous work on pinacol coupling and this work.
This journal is © The Royal Society of Chemistry 2019
Chem. Sci.

View Article Online
Chemical Science
Edge Article
Table 1 Optimization of the reaction conditionsa
without the use of any metal. Inspired by our previous work on
[Ni]/N2H4 as the reductive system to realize diaryl reductive
coupling reactions,6 we envisioned the feasibility of employing
N2H4 as a clean reductant for the pinacol coupling, bearing in
mind the innate reductive coupling nature in such a trans-
formation. However, to use N2H4 as the reductant to directly
reduce ketones to the ketyl radicals via the SET process could be
Yield (%)
highly challenging due to the unmatched redox potentials (e.g.
red
N2H4
(x equiv.)
acetophenone: E ¼ ꢀ1.85 V vs. normal hydrogen electrode
1/2
Entry
Solvent
conv. (%)
3a
4a
red
(NHE); N2H4: E ¼ ꢀ1.49 V vs. NHE).5a,7
1/2
Faced with this dilemma and inspired by the recent work of
Martin et al.,8 in which the aromatic ketone was identied as an
efficient hydrogen-atom-transfer (HAT) reagent in its excited
state, we anticipated the possibility of realizing the pinacol
coupling reaction with N2H4 via HAT instead of the well-known
SET mechanism. In fact, there has been a long history of the use
of aromatic ketones as HAT reagents in their excited states,
pioneered by Norrish,9 Yang10 and others.11 The aromatic
ketone can be excited under UV light irradiation to form the
excited triplet state to act as a 1,2-diradical, which is very
effective for the radical HAT process because of the electrophilic
properties of the excited oxygen radical.8,11a,d On the other hand,
N2H4 is potentially able to be used as a hydrogen atom donor in
this HAT process due to the expected favorable thermody-
namics: the relatively weak hydrazine N–H bond with a bond
dissociation energy (BDE) of approximately 277 kJ molꢀ1 is
1
2
3
4
5
6
H2O
MeOH
EtOAc
PhCF3
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0
0.75
0.75
0.75
1.0
0.75
0.75
90
50
60
50
53
73
77
14
12
84
98
51
99
42
42
12
10
38
42
47
62
68
—
2
2
2
2
2
2
2
—
—
2
4
2
4
2
1
Benzene
1,4-Dioxane
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
7
8b
9
—
72
10
11c
12c,d
13c
14c,f
15c,g
80 (80)e
30
81
27
32
a
General reaction conditions: acetophenone (0.2 mmol, 1 equiv.) and
N2H4$H2O (x equiv.) in solvents (1 mL) were stirred under argon for
12 h with UV light (254 nm) irradiation at 25 ꢂC; starting material
conversion and NMR yields were given with 1,3,5-trimethoxybenzene
as the internal standard; yields were calculated based on
replaced by a strong alcohol O–H bond with a BDE of ꢁ443 kJ
b
c
d
molꢀ1
.
12
acetophenone. Without UV light. 24 h instead. Under air instead
e
f
of argon. Isolated yield. MeNH–NHMe (1 equiv.) was used instead
of N2H4. g iPrOH (0.75 equiv.) was used instead of N2H4. For
optimization of other reactants, please see the ESI.
Based on the above mechanistic analysis,
a working
hypothesis is proposed in Scheme 1b. Initially, the 1,2-diradical
can be formed when the aromatic ketone is excited by UV light.
This is followed by hydrogen atom abstraction from N2H4 that
generates the ketyl radical – the key precursor in the pathway to
$
Control experiments (entries 8 and 9) revealed that both UV
light and hydrazine were vital for this transformation to
proceed. By increasing the hydrazine amount to 0.75 equiv. and
prolonging the reaction time to 24 h (entries 10 and 11),
delightfully, the desired pinacol product 3a could be obtained
in 80% isolated yield (entry 11). The argon atmosphere was
found to be necessary for this transformation, as decreased
yield (30%) was observed when the reaction was run under air
instead (entries 11 vs. 12). By further increasing the hydrazine
amount to 1.0 equiv., the yield could not be increased accord-
ingly. Other reductants, such as hydrazine derivatives (entry 14
and Table S1 in the ESI†) and iPrOH (entry 15), showed inferior
reactivities compared to hydrazine.
With the optimized reaction conditions in hand, we next
examined the reaction scope of aromatic ketones as shown in
Table 2. Acetophenones attached with electron-donating groups
such as methoxy, phenoxy, and Boc-protected amine worked
well in this transformation, affording the pinacol products (3b,
3c and 3f) in moderate to high yields (64–81%). It was note-
worthy that cyclic aromatic ketone, e.g. 4-chromanone, was able
to generate the pinacol product 3d in good yield (82%), and
multiple electron-donating substituents such as 2,4,6-trime-
thoxy- acetophenone gave the product 3e in 81% yield. Aceto-
phenones bearing electron-withdrawing substituents, such as
pinacol. Meanwhile, N2H3 may be produced and then by
another HAT, unstable diimide (N2H2) can be afforded, readily
decomposing to N2 and H2 gases as by-products to be released
out from the reaction system to further move forward this
transformation.6,13 With this working hypothesis in mind, we
report a light-driven metal-free pinacol coupling utilizing N2H4,
for the rst time, as a clean HAT reductant with traceless non-
toxic N2 and H2 gases generated in situ as sole by-products.
2. Results and discussion
To investigate the feasibility of our hypothesis, we initially
examined the reaction by using acetophenone (0.2 mmol, 1
equiv.) as the model substrate with hydrazine monohydrate (0.1
mmol, 0.5 equiv.) as the reductant in 1 mL H2O at 25 ꢂC with UV
light irradiation (254 nm) for 12 h under an argon atmosphere
(Table 1, entry 1). The desired corresponding pinacol product,
2,3-diphenylbutane-2,3-diol (3a), could be obtained in 12%
NMR yield along with acetophenone hydrazone and azine as by-
products that result from the condensation of acetophenone
and hydrazine. To slow down the formation of hydrazone and
azine, non-protic solvents were tested (entries 3–7) with CH3CN
showing the best efficiency to produce 3a with 68% NMR yield
(entry 7).
Chem. Sci.
This journal is © The Royal Society of Chemistry 2019

View Article Online
Edge Article
Chemical Science
Table 2 Substrate scope of aromatic ketonesa
a
General reaction conditions: ketone (0.2 mmol, 1 equiv.) and N2H4$H2O (0.75 equiv.) in CH3CN (1 mL) were stirred under argon for 24 h under UV
light (254 nm) irradiation at 25 ꢂC; isolated yields were given. b 1 equiv. of N2H4$H2O was used. c A xenon light was used. d Benzene was used as the
solvent. e 2 equiv. of N2H4$H2O were used.
–F, –Cl, –CN and –CF3 (3g, 3h, 3j, 3k and 3l), were also effective 3n) in moderate yields, 63% and 72% respectively. Benzophe-
in this transformation, albeit giving slightly lower yields (63– none-type compounds reacted in a similar fashion to aceto-
70%) compared to electron-donating ones. Acetophenone phenones, generating the corresponding pinacol products (3o–
bearing both electron-donating and electron-withdrawing 3u) in moderate to good yields. For the scope of heteroaryl
substituents, such as 2-F-4-OMe-acetophenone, could afford the ketones, we found that some heteroaryl ketones, containing
product 3i in 88% yield. However, 4-Br-acetophenone was an pyrrole, thiophene and furan units (3v–3z), could afford the
ineffective substrate, where the reductive photo-cleavage of the corresponding pinacol products in moderate yields (23% to
C–Br bond under UV irradiation was observed.14 Changing the 57%). To demonstrate the synthetic application of this protocol,
methyl group in acetophenone to larger ethyl and cyclopropyl a gram-scale reaction with benzophenone (1.09 g) as a model
groups could also produce the corresponding products (3m and substrate was tested under standard conditions; and
This journal is © The Royal Society of Chemistry 2019
Chem. Sci.

View Article Online
Chemical Science
Edge Article
delightfully, 89% isolated yield could be obtained. Unfortu- CH3CN to CD3CN with benzophenone as the model substrate
nately, aldehydes, aliphatic ketones and aromatic imines were due to the ease of analyzing the crude NMR of the starting
not compatible with this transformation probably due to their material and product (Fig. 1a). It was found that all the protons
fast condensation with hydrazine to generate hydrazone and were derived from the N2H4 instead of the acetonitrile solvent,
azine by-products.
since no deuterium was incorporated into the benzopinacol (3o)
Next, the feasibility of realizing the cross-pinacol coupling product and the benzhydrol (4o) by-product as conrmed by
was examined by mixing acetophenone and benzophenone-type deuterium NMR (2D-NMR) (Fig. 1a)
compounds (Table 3 and see ESI† for details). It was found out
Secondly, 2 equiv. of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl
that the acetophenones attached with electron-withdrawing (TEMPO) or butylated hydroxytoluene (BHT), as radical inhibi-
groups such as 4-CF3 and 4-Cl gave better selectivity and yields tors, were added into the reaction system under the standard
of cross-pinacol products, compared to acetophenone (entries conditions. The reaction was totally suppressed when TEMPO
1–3) and 4-OMe acetophenone (see ESI† for details). Benzo- was added, with the TEMPO being mainly reduced to 2,2,6,6-
phenones with –F and –CH3 substituents showed similar reac- tetramethylpiperidine; whereas in the case of BHT, the reaction
tivities to simple benzophenone (entries 2, 4 and 5). Finally, proceeded slower compared to the one without the inhibitor,
benzophenone attached with –OMe could not further increase demonstrating that the radical based mechanism was involved
the cross-pinacol product selectivity and yield (entry 6).
in this transformation (Fig. 1b).25 Thirdly, the uorescence
quenching experiment between benzophenone and N2H4 was
performed (see ESI† for details). The uorescence of benzo-
phenone could be efficiently quenched by N2H4, suggesting the
existence of a strong interaction between the excited benzo-
phenone and N2H4 (Fig. 1c). From the three mechanistic studies
shown above, it was reasonable to propose that the ketyl radical
was formed by the HAT process between the 1,2-diradical,
generated by the photoexcitation of the aromatic ketone and
N2H4.
3. Mechanistic studies
3.1 Identication of the ketyl radical formation process
The control experiments in Table 1 (entries 8 and 9) showed that
without UV light or N2H4, the desired pinacol product 3a could
not be generated, indicating that the ketyl radical could be
formed from the HAT process between the photo-excited 1,2-
diradical and N2H4. To further conrm this process, rstly, the
origin of protons was studied by changing the solvent from
3.2 Identication of the HAT behavior of N2H4
3.2.1 Determination of the number of hydrogens reacted in
N2H4. Firstly, the stability of N2H4 was studied: N2H4 was very
stable and did not decompose under the standard conditions
(see ESI† for details). Secondly, since N2H4 had four protons in
total, it potentially had two possible pathways to donate its
hydrogens: pathway A: donating all four hydrogens to generate
N2; pathway B: only two hydrogens being donated to form the
unstable diimide (N2H2), which then readily decomposes to N2
and H2 gases. To understand how many hydrogens were used in
this reaction, in situ control experiments by limiting various
N2H4 amounts were run in a quartz NMR tube to directly
monitor the reactions by 1H NMR (Scheme 2). For example,
when 0.25 equiv. of N2H4 was used, only around half conversion
(42%) was obtained with around 42% product yield, in the
presence of 1 equiv. of hydrogen atoms (4 ꢃ 0.25 equiv.) and the
N2H4 was completely consumed as shown by NMR (see ESI† for
details), which was further conrmed by the absence of hydra-
zone or azine when benzaldehyde was added into the NMR tube
aer the reaction. The evidence clearly stated that only two
hydrogens in N2H4 were involved in this transformation,
favoring pathway B over A.
Table 3 Attempts of cross-pinacol couplinga
3.2.2 Evidence for diimide (N2H2). Due to the instability of
the diimide (N2H2), it would be very difficult to obtain the direct
evidence.15 Recent work reported by Minnaard and Lin showed
that alkenes could be efficiently hydrogenated to alkanes by the
in situ generated N2H2 from N2H4.13b,16 Therefore, 4-methox-
ystyrene was added into the reaction system as the indicator of
N2H2 under the standard conditions, and the hydrogenated
product 4-ethylanisole could be generated, indicating that N2H2
a
General reaction conditions: acetophenone-type compounds (0.1
mmol, 1 equiv.), benzophenone-type compounds (0.1 mmol, 1 equiv.),
and N2H4$H2O (0.15 mmol, 1.5 equiv.) in CH3CN (1 mL) were stirred
under argon for 24 h under UV light (254 nm) irradiation at 25 ꢂC.
b
NMR yields were given with mesitylene as the internal standard.
c
d
N2H4$H2O (0.2 mmol, 2 equiv.) was used instead. Ratio was
determined by analysis of crude 1H-NMR.
Chem. Sci.
This journal is © The Royal Society of Chemistry 2019

View Article Online
Edge Article
Chemical Science
Fig. 1 Examination of the mechanism of ketyl radical formation.
Scheme 2 The number of hydrogens reacted in N2H4.
was likely formed under the standard conditions (Scheme 3a).
Moreover, when 1,2-dimethylhydrazine was used as the reduc-
tant instead of N2H4, MeN]NMe, the N2H2 analogue, was
detected in the gas phase (see ESI† for details),17 further indi-
cating the formation of N2H2 (Scheme 3b). Finally, analysis of
the gas phase of the standard reaction conditions showed the
presence of N2 but not NH3 (see ESI† for details). With all the
above information shown, the reaction pathway B for N2H4 was
more feasible.
Scheme 3 Evidence of N2H2.
dimerization of two free radicals, simply because of the
extremely low concentration and short life-times of the active
radical species in solution,19 although it may represent the
apparent results. Instead, another possible route to form the C–
C bond is via the ketyl radical addition to the unsaturated C]O
(Scheme 4, right). Therefore, we were wondering whether the
3.3 Mechanism of the pinacol C–C bond formation process
Historically, the commonly proposed mechanism for the UV-
irradiation assisted benzopinacol type C–C bond formation was
the homo-dimerization of two ketyl radicals (Scheme 4,
le).11d,18 However, from modern perspectives, it is arguable that
the C–C bond formation step arises from the homo- Scheme 4 Two representative C–C formation mechanisms.
This journal is © The Royal Society of Chemistry 2019
Chem. Sci.

View Article Online
Chemical Science
Edge Article
kinetics toolkit could be used to differentiate the two mecha-
nisms to uncover this “historical mystery” of the C–C bond
formation mechanism in this pinacol reaction.
Initially, the rate determining step (RDS) of this trans-
formation was studied. Firstly, the kinetic isotope effect (KIE)
was used to identify whether the HAT process was the RDS or
not. The KIE (kH/kD) was around 1 when the N2D4 was used
compared to the normal N2H4, indicating that the HAT process
was not the RDS but a fast step (Scheme 5 and see ESI† for
details). Since this reaction was initiated by UV irradiation, the
photoexcitation might be the RDS. To examine this assumption,
the reaction was run under UV irradiation with its light intensity
reduced to 2/3 of its original one; and it was found that the
reaction rate was reduced accordingly (vobs (2/3I0)/vobs (I0) z
1.99/3 z 2/3 (theoretical number), see ESI† for details), sug-
gesting that the photoexcitation was the RDS.
With the above kinetic information, if the mechanism for C–
C bond formation was via ketyl radical homo-dimerization, the
Scheme 6 The B3LYP/6-31G(d,p) energy profile of the reaction.
vobs (observed reaction rate) would be directly proportional to
2
the I0 (the square of the light intensity). However, this out and thermodynamic functions were calculated for the stan-
dard-state temperature 298.15 K and concentration 1 mol Lꢀ1 for
assumption was not correct because the vobs was directly
all species in the ground electronic states.
proportional to the I0, as stated before. On the other hand, if the
mechanism was via ketyl radical addition to the unsaturated
C]O, the vobs would be directly proportional to the I0, which
was very consistent with the experimental data. Thus, the latter
one was the more likely mechanism (see ESI† for details).
The stable intermediate structures and transition states are
shown in Scheme 6 together with their energies (the free energy
diagram is shown in the ESI†). For acetophenone, the intense UV-
Vis absorption peak is calculated to lie at 239 nm (5.18 eV), in
agreement with the experimentally observed transition (5.17 eV).23
Our excited state modeling also shows that a manifold of the
excited triplet states of acetophenone lies between 3.31 and 3.35
eV above the ground state. This characterization is consistent
with previous studies23 that show that an excited acetophenone
undergoes vibrationally assisted intersystem crossing into
a manifold of triplet states to generate the 1,2-diradical (Scheme
6). Our calculations indicate that the HAT from the triplet-state
acetophenone to hydrazine is a barrierless process that leads to
the formation of the ketyl radical bound to N2H3
In the next major step of the reaction, the ketyl radical in its
electronic ground state still bound to N2H3 forms the carbon–
carbon bond with another ground-state acetophenone mole-
cule. Unsurprisingly, the carbon–carbon bond cannot be
stabilized without another HAT from the nearby N2H3 to the
3.4 DFT study of the mechanism
Density functional theory (DFT) calculations were carried out in
order to verify the mechanism proposed based on the experi-
mental study and to gain detailed insights into elementary steps
and structural transformations along the pathway. Acetophenone
(1a) reaction with hydrazine was chosen as a model of the pinacol
coupling in calculations. All calculations were performed using
the Gaussian soware package (version 16, Revision B.01). The
B3LYP approximation20 corrected to account for dispersion
interactions21 was used as the exchange-correlation functional.
The 6-31G(d,p) basis set was employed to represent molecular
orbitals. Excited state calculations were performed using time-
dependent DFT. Acetonitrile solvent was represented implicitly
using the polarizable continuum model in the integral equation
formalism.22 Aer structures of stable intermediates and transi-
tion states were optimized, frequency calculations were carried
$
.
$
$
incoming acetophenone molecule. This is consistent with the
observation of Glorius et al., who noted that the radical addition
to C]O is fully reversible without the assistance of hydrogen.24
Notably, it was found that the second HAT and C–C coupling
can happen simultaneously via the transition state (TS) shown
in Scheme 6. In the nal step, the diimide N2H2 formed in the
previous step decomposes into N2 and H2.
The results of computational modeling are fully consistent
with the experimental observations and suggest that the energy
the system acquires aer the excitation is sufficient to overcome
the transition state associated with the C–C bond formation.
4. Conclusions
We have developed a metal-free and clean pinacol coupling
Scheme 5 KIE studies.
protocol enabled by light with N2H4, for the rst time, as a HAT
Chem. Sci.
This journal is © The Royal Society of Chemistry 2019

View Article Online
Edge Article
Chemical Science
reductant under very mild conditions (room temperature). The
reaction produces only traceless non-toxic N2 and H2 gases as by-
products. The protocol solves the long-standing metal waste
issues in the classical pinacol coupling reactions and has a rela-
tively broad aromatic ketone scope and functional group toler-
723; (c) V. V. Pavlishchuk and A. W. Addison, Inorg. Chim.
Acta, 2000, 298, 97–102.
8 Y. Shen, Y. Gu and R. Martin, J. Am. Chem. Soc., 2018, 140,
12200–12209.
9 R. G. W. Norrish and C. H. Bamford, Nature, 1937, 140, 195–196.
ance. Potential synthetic applications are demonstrated by 10 N. C. Yang and D. D. H. Yang, J. Am. Chem. Soc., 1958, 80,
a gram-scale reaction. Furthermore, the fundamental steps 2913–2914.
regarding the mechanism such as the processes of ketyl radical 11 (a) C. Chen, Org. Biomol. Chem., 2016, 14, 8641–8647; (b)
formation, the HAT behavior of N2H4 and the C–C bond forma-
tion of the product were extensively studied experimentally and
computationally.
W. Liu, N. Chen, X. Yang, L. Li and C. J. Li, Chem. Commun.,
2016, 52, 13120–13123; (c) W. B. Liu, X. B. Yang, Z. Z. Zhou
and C. J. Li, Chem, 2017, 2, 688–702; (d) S. G. Cohen,
A. Parola and G. H. Parsons, Chem. Rev., 1973, 73, 141–161.
12 Y.-R. Luo, Comprehensive handbook of chemical bond energies,
CRC press, 2007.
Conflicts of interest
There are no conicts to declare.
13 (a) K. D. Kim and J. H. Lee, Org. Lett., 2018, 20, 7712–7716; (b)
C. Smit, M. W. Fraaije and A. J. Minnaard, J. Org. Chem.,
2008, 73, 9482–9485; (c) D. Sellmann and A. Hennige,
Angew. Chem., Int. Ed., 1997, 36, 276–278.
Acknowledgements
We are grateful to the Canada Research Chair Foundation (to C.- 14 D. Cao, C. Yan, P. Zhou, H. Zeng and C. J. Li, Chem.
J. Li), the CFI, FRQNT Center for Green Chemistry and Catalysis, Commun., 2019, 55, 767–770.
NSERC, and McGill University for support of our research. R. Z. 15 (a) S. Hunig, H. R. Muller and W. Thier, Angew. Chem., Int.
¨
¨
K. acknowledges funding by NSERC through the Discovery
Grant (RGPIN-2016-05059). The authors are grateful to
Ed., 1965, 4, 271–280; (b) D. Sellmann and A. Hennige,
Angew. Chem., Int. Ed., 1997, 36, 276–278.
Compute Canada for computer time and thank Siting Ni for 16 (a) D. Leow, Y. H. Chen, T. H. Hung, Y. Su and Y. Z. Lin, Eur.
assistance with UV-visible and uorescence spectra measure-
ments. Z. Qiu is grateful to McGill's Chemistry Department for
the Major Scholarship and Pall Dissertation Award. D. Castillo-
J. Org. Chem., 2014, 2014, 7347–7352; (b) B. Pieber,
S. T. Martinez, D. Cantillo and C. O. Kappe, Angew. Chem.,
Int. Ed., 2013, 52, 10241–10244.
Pazos thanks CONACYT Mexico (2018-000009-01EXTF-00413) 17 B. N. Kenessov, J. A. Koziel, T. Grotenhuis and L. Carlsen,
for nancial support.
Anal. Chim. Acta, 2010, 674, 32–39.
18 (a) J. N. Pitts, R. L. Letsinger, R. P. Taylor, J. M. Patterson,
G. Recktenwald and R. B. Martin, J. Am. Chem. Soc., 1959,
81, 1068–1077; (b) S. G. Cohen and R. J. Baumgarten, J.
Am. Chem. Soc., 1967, 89, 3471–3475.
19 (a) H. Fischer, Chem. Rev., 2001, 101, 3581–3610; (b)
D. Leifert and A. Studer, Angew. Chem., Int. Ed., 2019, DOI:
10.1002/anie.201903726.
Notes and references
1 T. Newhouse, P. S. Baran and R. W. Hoffmann, Chem. Soc.
Rev., 2009, 38, 3010–3021.
2 (a) T. Hirao, Catalytic Reductive Coupling of Carbonyl
Compounds
– The Pinacol Coupling Reaction in Metal
Catalyzed Reductive C–C Bond Formation, ed. M. J. Krische, 20 (a) A. D. Becke, J. Chem. Phys., 1993, 98, 5648–5652; (b)
Springer Berlin Heidelberg, Berlin, Heidelberg, 2007,
ch.120, pp. 53–75; (b) T. Wirth, Angew. Chem., Int. Ed.,
1996, 35, 61–63.
C. Lee, W. Yang and R. G. Parr, Phys. Rev. B, 1988, 37, 785–
789; (c) S. H. Vosko, L. Wilk and M. Nusair, Can. J. Phys.,
1980, 58, 1200–1211.
3 (a) B. K. Hazarika and D. K. Dutta, Synth. Commun., 2011, 41, 21 S. Grimme, J. Antony, S. Ehrlich and H. Krieg, J. Chem. Phys.,
1088–1093; (b) T. Mandal, S. Jana and J. Dash, Eur. J. Org.
2010, 132, 154104.
Chem., 2017, 4972–4983; (c) G. M. Robertson, in 22 G. Scalmani and M. J. Frisch, J. Chem. Phys., 2010, 132,
Comprehensive Organic Synthesis, ed. B. M. Trost and I.
114110.
Fleming, Pergamon, Oxford, 1991, pp. 563–611, DOI: 23 (a) M. Huix-Rotllant and N. Ferre, J. Chem. Phys., 2014, 140,
´
´
10.1016/b978-0-08-052349-1.00073-1.
134305; (b) M. Huix-Rotllant, I. Burghardt and N. Ferre, C. R.
4 (a) P. Anastas and N. Eghbali, Chem. Soc. Rev., 2010, 39, 301–
312; (b) C. J. Li, Green Chem., 2016, 18, 1836–1838.
5 (a) M. Nakajima, E. Fava, S. Loescher, Z. Jiang and
M. Rueping, Angew. Chem., Int. Ed., 2015, 54, 8828–8832;
(b) Q. Xia, J. Dong, H. Song and Q. Wang, Chem.–Eur. J.,
2019, 25, 2949–2961.
6 L. Lv, Z. Qiu, J. Li, M. Liu and C. J. Li, Nat. Commun., 2018, 9,
4739.
7 (a) T. Shimada, A. Tamaki, H. Nakai and T. Homma,
Electrochemistry, 2007, 75, 45–49; (b) H. G. Roth,
N. A. Romero and D. A. Nicewicz, Synlett, 2016, 27, 714–
Chim., 2016, 19, 50–56.
24 (a) L. Pitzer, F. Sandfort, F. Strieth-Kalthoff and F. Glorius, J.
Am. Chem. Soc., 2017, 139, 13652–13655; (b) L. Pitzer,
F. Sandfort, F. Strieth-Kalthoff and F. Glorius, Angew.
Chem., Int. Ed., 2018, 57, 16219–16223.
25 The corresponding ketyl radical TEMPO and BHT adducts
could be detected in trace amounts by ESI-HRMS. For
TEMPO, HRMS (ESI): found for the adduct C22H29O2NNa
([M + Na]+) 362.2104, calculated 362.2091; for BHT, HRMS
(ESI): found for the adduct C28H34O2Na ([M + Na]+)
425.2466, calculated 425.2451.
This journal is © The Royal Society of Chemistry 2019
Chem. Sci.