Homogeneous Hydrogenation with a Cobalt/Tetraphosphine Catalyst: A Superior Hydride Donor for Polar Double Bonds and N-Heteroarenes

Article abstract of DOI:10.1021/jacs.9b11070

The development of catalysts based on earth abundant metals in place of noble metals is becoming a central topic of catalysis. We herein report a cobalt/tetraphosphine complex-catalyzed homogeneous hydrogenation of polar unsaturated compounds using an air- and moisture-stable and scalable precatalyst. By activation with potassium hydroxide, this cobalt system shows both high efficiency (up to 24 000 TON and 12 000 h^-1 TOF) and excellent chemoselectivities with various aldehydes, ketones, imines, and even N-heteroarenes. The preference for 1,2-reduction over 1,4-reduction makes this method an efficient way to prepare allylic alcohols and amines. Meanwhile, efficient hydrogenation of the challenging N-heteroarenes is also furnished with excellent functional group tolerance. Mechanistic studies and control experiments demonstrated that a Co^IH complex functions as a strong hydride donor in the catalytic cycle. Each cobalt intermediate on the catalytic cycle was characterized, and a plausible outer-sphere mechanism was proposed. Noteworthy, external inorganic base plays multiple roles in this reaction and functions in almost every step of the catalytic cycle.

Full text of DOI:10.1021/jacs.9b11070

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Article
Homogeneous hydrogenation with a cobalt/tetraphosphine catalyst:
a superior hydride donor for polar double bonds and N-heteroarenes
Ya-Nan Duan, Xiaoyong Du, Zhikai Cui, Yiqun Zeng, Yufeng Liu, Tilong Yang, Jialin Wen, and Xumu Zhang
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 02 Dec 2019
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Homogeneous hydrogenation with a cobalt/tetraphosphine catalyst: a su-
perior hydride donor for polar double bonds and N-heteroarenes
Ya-Nan Duan†,∥ , Xiaoyong Du†,∥ , Zhikai Cui†, Yiqun Zeng†, Yufeng Liu†, Tilong Yang†, Jialin Wen*,†,‡
and Xumu Zhang*,†,§
†Department of Chemistry, Southern University of Science and Technology, Shenzhen, China;
‡Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, China;
§Shenzhen Grubbs Institute, Southern University of Science and Technology, Shenzhen, China.
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ABSTRACT
The development of catalysts based on earth abundant metals in place of noble metals is becoming a central topic of catalysis.
We herein report a cobalt/tetraphosphinecomplex catalyzed homogenous hydrogenation of polar unsaturated compounds using
an air- and moisture-stable and scalable precatalyst. By activation with potassium hydroxide, this cobalt system shows both
high efficiency (up to 24000 TON and 12000 h-1 TOF) and excellent chemoselectivities with various aldehydes, ketones, imines
and even N-heteroarenes. The preference for 1,2-reduction over 1,4-reduction makes this method an efficient way to prepare
allylic alcohols and amines. Meanwhile, efficient hydrogenation of the challenging N-heteroarenes is also furnished with ex-
cellent functional group tolerance. Mechanistic studies and control experiments demonstrated that a CoIH complex functions
as strong hydride donor in the catalytic cycle. Each cobalt intermediate on the catalytic cycle was characterized and a plausible
outer-sphere mechanism was proposed. Noteworthy, external inorganic base plays multiple roles in this reaction and functions
in almost every step of the catalytic cycle.
INTRODUCTION
The catalytic reduction of polar unsaturated compounds to their partially or completely saturated congers is of particular interest
in both organic synthesis and industrial production. Traditional transition-metal-catalyzed homogeneous hydrogenation of polar
unsaturated compounds involves the coordination of heteroatoms to the metal center, followed by the migratory insertion of
metal hydride to the double bonds1. In such situation, the possible poisoning of the catalyst by substrates or their hydrogenated
products might decrease the catalytic efficiency to varying degrees. Contrary to this “inner-sphere” mechanism, “outer-sphere”
hydrogenation does not involve the coordination of the substrate, usually giving a higher efficiency2. Developing general,
reliable and efficient catalytic systems in transition-metal-catalyzed homogeneous hydrogenation is highly desirable both in
academics and industry. As a continuing interest in transition metal catalyzed homogeneous hydrogenation, we are seeking for
a single catalytic system for various type of challenging substrates. In our perspective, two main factors might help to devel-
oping an ideal hydride donor for unsaturated polar compounds: 1) Coordinating-saturation of the metal center, not only inhib-
iting the possible catalyst poisoning but ensuring the chemoselectivity; 2) Superb thermodynamic hydricity,
The attempt of replacing precious platinum group metals (Rh, Ru, Pd, Os, Ir and Pd) with earth abundant metals in catalysis
has never ceased3-15. The Achilles’ heel of earth abundant metal catalyzed homogeneous hydrogenation lies in reliability, gen-
erality and the relatively high catalyst loading. The development of cobalt-catalyzed hydrogenation was slower than iron.
Though impressive works in cobalt mediated C=O bond hydrogenation by Hanson, Wolf and von Wangelin, Kempe, Zhang
and Xu have been reported16-19, most of the ligands of these cobalt catalysts are either air-sensitive or difficult to synthesize at
a large scale, thus impeding their applications. Very recently, Liu and co-workers reported a highly practical NHC-cobalt
catalyst for C=O hydrogenation20. The NHC ligands were tunable, air-stable and easily accessible. However, chemoselective
reduction of aldehydes in the presence of C=C bonds using non-precious metals was still rarely reported21-27. To the best of our
knowledge, only one cobalt catalyst, a triazine-based cobalt complex (PN5P-Co) developed by Kempe and co-workers, has
been reported for chemoselective reduction of aldehydes in the presence of conjugated C=C bonds (Figure 1A)18. As for imine
hydrogenation, it is still a challenge in the subfield of earth-abundant metal catalysis16-17,28. And the selective C=N hydrogena-
tion of conjugated imines to allylic amines were still not achieved with nonprecious or even noble metal catalysts so far29-30
.
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Hydrogenation of aromatic heterocycles using non-precious metals like iron or cobalt is rarely reported and still a big challenge
mainly due to the inherent aromatic stability and the possible poisoning of the catalyst by N-heteroarenes or their hydrogenated
products31-34. Jones and co-workers found that iron or cobalt pincer catalyst was able to perform acceptorless catalytic dehy-
drogenation and hydrogenation of N-heterocycles (Figure 1B, a)35-36. Very recently, Beller and co-workers showed that a
Co/tetraphos system enabled general and chemoselective hydrogenation of quinolines and related heterocylcles with a high
tolerance for other reducible groups (Figure 1B, b)37. However, there is still no one general catalytic system that not only
enables efficient hydrogenation of all above types of substrates but shows high chemoselectivity.
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Guided by the above rationales that coordinating-saturation and superb hydricity of the metal hydride might benefit to de-
veloping efficient and chemoselective hydrogenation catalysts, the ligand P2C-PPh22NPh2 captured our attention. This tetraphos-
phine ligand was firstly reported to be utilized in the electrocatalytic hydrogen production but without any further use in cata-
lytic hydrogenation at present38. As reported by Wiedner and Bullock, [CoI(P2C-PPh22NPh2)H], though without isolation and
characterization, has a superior thermodynamic hydricity of 31.8 kcal/mol (in acetonitrile) which represents the best hydride
donor of the first-row metal hydrides that have been experimentally determined39-40. This cobalt hydride is not only with super
hydricity but coordination-saturated, which we envisioned that would be promising reducing species for chemoselective hy-
drogenation of polar unsaturated compounds.
Figure 1. Cobalt catalysts for chemoselective hydrogenation of conjugated C=O and C=N bonds and N-heteroarenes.
Herein, we report on a highly efficient and general cobalt catalytic system for hydrogenation of a wide range of polar un-
saturated compounds utilizing oxygen and moisture-insensitive and scalable precatalyst, which could be readily activated by
potassium hydroxide. Such mild activation protocol greatly simplified the low-oxidation-state cobalt catalysis. Challenging
substrates, such as conjugated aldehydes, imines and even N-heteroaromatics, are reduced by molecular hydrogen with remark-
able chemoselectivity over C=C bonds and desired compatibility with a wide variety of functional groups. It should be pointed
out that the reduction of N-heteroaromatic compounds under a basic condition has been a historically challenging task since
Brønsted acids were normally applied to activate N-heteroaromatic compounds. Moreover, a plausible catalytic cycle is pro-
posed which was evidenced by control and stoichiometric experiments and CoIH is verified to be the real reducing species.
RESULTS AND DISCUSSION
Chemoselective hydrogenation of conjugated aldehydes, ketones and imines. After systematic condition evaluation (for
details, see Table S1), the optimal reaction condition was established. Then, the reaction scope of this [Co]/L1 catalytic system
was explored. A series of α,β-unsaturated aldehydes were tested with 0.1 mol% catalyst loading under the optimized condition
(Figure 2). Cinnamaldehyde and its derivatives were reduced smoothly under the reaction conditions, affording the
corresponding cinnamic alcohols 2aa-2af in 91-99% isolated yields. Altering substituents on the acrolein unit did not influence
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the reactivity in the 1,2-reduction of the conjugated aldehydes. Hydrogenation of α-substituted cinnamaldehyde were occurred
smoothly to give 2ag-2ai in high yields. Heteroaromatic α,β-unsaturated aldehydes 1aj and 1ak were efficiently hydrogenated
to give the desired product in nearly quantitative yield. Multiple conjugated aldehyde 2al underwent hydrogenation successfully
to give C=O bond reductive product 2al in 98% yield. It should be noted that the [Co]/L1 system is highly chemoselective not
only for the hydrogenation of α,β-unsaturated aldehydes but also for aldehydes with non-conjugated C=C bond. The
hydrogenation of citral 1am and 4-vinylbenzaldehyde 1an exclusively formed the C=O reduction products 2am and 2an in
97% and 95% yield, respectively. No C=C double bond hydrogenation products were detected in those reactions. Note that
secondary allylic alcohol product 2ao was also well produced via selective hydrogenation of conjugated ketone 1ao.
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The success of this catalytic system for chemoselective hydrogenation of α,β-unsaturated aldehydes inspired us to exploit
its reaction scope to more challenging substrate, α,β-unsaturated aldimine. The lower polarization of C=N bonds requires a
higher hydricity of metal hydride complexes, which might cause a problem for carbonyl reduction catalysts. We are pleased to
find that when the reaction temperature of α,β-unsaturated aldimines substrates was lowered to 50 oC, the reaction efficiency
and C=N chemoselectivity were satisfactory. Complex 3 catalyzed the selective reduction of α,β-unsaturated aldimine 1ap to
the corresponding allylic amine 2ap in 97% yield. Substituents such as methyl, dimethylamino and methoxyl, at the para
position of the phenyl ring are tolerated under the reaction conditions, furnishing the hydrogenation products (2aq-2as) in 98-
99% isolated yields. The O-containing heteroaromatic α,β-unsaturated aldimine 1at underwent selective hydrogenation giving
the desired product in 97% yield. α,β-Unsaturated aldimines with other N-aryl group (1au-1aw) also showed high reactivity.
Once again, conjugated C=C bonds were retained in this catalytic reaction, demonstrating a high chemoselectivity for polar
C=N reduction.
When expanding the substrate scope, it was delightful to find that various of aldehydes, ketones and imines were reduced
efficiently under the reaction conditions. Aromatic aldehydes bearing electron-withdrawing or electron-donating groups as well
as other easily reducible groups (-CN and -CO2Me) were efficiently hydrogenated (2ba-2bi). The reaction of alkyl aldehydes
afford the corresponding alcohols 2bk-2bm in 92-99% isolated yields. Hydrogenation of aromatic aldehydes bearing ortho-
coordinative groups has been a challenge due to chelating effect. However, under our catalytic conditions, 2-
hydroxybenzaldehyde 1bn was hydrogenated to give 2bn in 95% isolated yield, despite a little higher catalyst loading was
employed. Furthermore, strong coordinating heterocycles and groups such as pyridine (1bm-1br) and thiophene (1bs) and
phosphine (1bt) were tolerated. The reaction of ketones (1bu) and imines (1bx-1bz) were occurred smoothly, giving the
corresponding products in 96-99% yields, albeit with 1 mol% catalyst at 100 oC.
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a
Figure 2. Different types of C=O bonds and C=N bonds for hydrogenation. Conditions: 1 (0.2 mmol), 0.1 mol%
[CoII(L1)(CH3CN)](BF4)2 (0.01 M solution in CH3CN), KOH (10 mol%), solvent (1 mL) under 30 bar H2 at 60 oC over 24 h;
bWith 1 mol% of cobalt catalyst. cWith 0. 1 mol% of cobalt catalyst at 50 oC over 12 h. dWith 0. 1 mol% of cobalt catalyst at
e
f
o
room temperature over 12 h. Using 1,4-dioxane as the solvent instead of EtOH. With 1 mol% of catalyst at 100 C using
iPrOH as the solvent.
Hydrogenation of N-heteroaromatic compounds. Encouraged by the success in chemoselective hydrogenation of C=O and
C=N double bonds, we explored the application of this method in more challenging N-heteroaromatic compounds. Under a
minor-modified condition, quinolines bearing different groups, regardless of election-donating or electron-withdrawing, were
hydrogenated smoothly (Figure 3). The compatibility with unsaturated functionalities was also evaluated under this condition.
Cyano and ester groups survived in this transformation. To our delight, alkenyl and alkynyl groups (2cj-2ck) were retained,
showing an excellent selectivity to polar double bonds. Adding steric hindrance did not bring obvious decrease in reaction rates
(2cp-2ct). It is noteworthy that when reducing 2,2-biquinoline (1cs), only one of the quinoline rings was hydrogenated under
a harsher condition. Other N-heteroaromatics, such as isoquinoline (1da), quinoxalines (1db-1dd), benzo[g]quinoline (1de),
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acridine (1df), phenanthridine (1dg) and highly coordinative 1,10-phenanthroline derivatives (1dh-1dj) were all available sub-
strates for the [Co]/L1 system. Among them, quinoxalines, benzo[g]quinoline and acridine were hygrogenated using 1 mol%
of cobalt catalyst at 100 oC, providing hydrogenated products in modest to excellent yields (Figure 3, 2bb-2bg). When a little
higher temperature and catalyst dosage was utilized, a good result for isoquinoline hydrogenation was obtained. Remarkably,
hydrogenation of 1,10-phenanthrolines, a challenging task due to the strong coordinating ability, also successfully proceeded.
Interestingly, only heterocycle ring was reduced (2dh-2dj). The partially reduced 1,2,3,4-tetrahydro-1,10-phenanthrolines al-
ways serve as significant ligands for olefin polymerization41.
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Figure 3. Homogeneous hydrogenation of N-heteroaromatic compounds. Conditions: 1 (0.2 mmol), 1 mol%
o
[CoII(L1)(CH3CN)](BF4)2 (0.01 M solution in CH3CN), KOH (10 mol%), iPrOH (1 mL) under 30 bar H2 at 100 C over 48
hours. aat 0.1 mol% catalyst loading. bUsing toluene as the solvent. cUsing 3 mol% catalyst at 120 oC and 50 bar H2.
Although this cobalt catalyst showed no reactivity to pyridine 1dk, partial hydrogenation of N-heteroarenes bearing cyano
group sitting 3-position was realized. Substrates 1ec-1ef were all partially hydrogenated to 1,4,5,6-tetrahydropyridine-3-car-
bonitrile congeners in excellent yields using 1 mol% of cobalt at 100 oC and 50 atm H2. 3-Cyanoquinoline (1ea) was partially
hydrogenated to 1,4-dihydroquinoline-3-carbonitrile in 95% isolated yield which represents the first example for partial hydro-
genation of cyano-substituted quinolines. Also, isoquinoline-4-carbonitrile (1eb) was reacted smoothly to give 1,2-dihydroiso-
quinoline-4-carbonitrile in excellent yield. The retention of this enamine structure was probably caused by the conjugation with
such an electron-withdrawing group as nitrile.
Scale-up reactions. To demonstrate the effectiveness and practicability of such catalytic system, several scale-up reactions
were conducted. Firstly, the cobalt precatalyst 3 was prepared on gram scale, and the protocol is quite easy to handle mainly
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owing to the air-stability and moisture-insensitivity of 3. Then, several high TON experiments were carried out. Citral reacted
with H2 efficiently, giving geraniol with 75% yield in 24 hours at 100 mmol scale (TON: 7500). And this precatalyst also
exhibits exceptionally high activity in the hydrogenation of 4-fluorobenzaldehyde (TON = 24000, TOF = 12000 h-1, for the
measurement of TOF, see Supporting Information). As for the more challenging N-heteroarene, quinoline could be hydrogen-
ated at 0.1 mol% catalyst loading on 1 mmol scale.
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Scheme 1. Scale-up reactions for catalyst preparation and hydrogenation reactions
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Activation of the precatalyst. To provide insight into the catalyst activation mode, several stoichiometric experiments were
carried out. Treatment of [CoII(L1)(CH3CN)](BF4)2 (3) with 10 equivalents of KOH in acetonitrile-d3 at room temperature for
48 h formed a diamagnetic, putative Co(I) species [CoI(L1)(CH3CN)(BF4)] (4) in 95% NMR yield (Scheme 2a). The reaction
progress in acetonitrile-d3 was monitored by 1H NMR spectroscopy and showed in Figure 4. The complete conversion of 3 to
the diamagnetic Co(I) species was achieved after 48 h when adding 10 equivalents of KOH to the reaction mixture (Figure 4b,
4c). In order to determine the identity of this Co species, 4 was independently prepared using a known procedure. The reaction
of 3 with 1.4 equivalents of potassium graphite in CH3CN at room temperature gave 50% isolated yield of the Co(I) complex
4 (Scheme 2b). The 1H NMR spectrum of isolated 4 was in accordance with the complex generated in situ from the reaction
between 3 and KOH (Figure 4d vs 4c).
Scheme 2. In Situ activation of [CoII(L1)(CH3CN)](BF4)2 to [CoI(L1)(CH3CN)(BF4)] by KOH through one-electron pathway.
These results indicated that the Co(II) species can be reduced or activated with KOH to form a low-oxidation-state Co(I)
species. This process typically requires external activation reagents, most of which are air- and moisture-sensitive organome-
tallic regents such as NaBEt3H42-50 and EtMgBr51-52. The challenges in handling, storage and transportation limit their industrial
application. Hence, efforts have been devoted to circumventing such limitations. For example, Thomas and co-workers reported
a simple method for the use of earth-abundant metal catalysts during alkene hydrosilylation and hydroboration by general
activation with NaOtBu53.
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Figure 4. (a) 1H NMR spectrum of 3 in acetonitrile-d3. (b) 1H NMR spectrum taken after 24 h when adding 10 equivalents of
KOH in acetonitrile-d3. (c) 1H NMR spectrum taken after 48 h. (d) 1H NMR spectrum of independently synthesized 4 in ace-
tonitrile-d3.
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Plausible pathways here include base-assisted disproportionation or in situ reduction. Disproportionation of a Co(II) typically
results in Co(I) with Co(III) species. However, the failure in observation of a Co(III) species disfavored this mechanism. On
the other hand, hydroxide and alkoxide ion might serve as a one-electron reducing agent54-55. Indeed, after adding radical
scavenger (e.g. TEMPO) the conversion from 3 to 4 was completely inhibited. In addition, in the presence of TEMPO, the
catalytic hydrogenation of aldehyde with 3 was also shut down. In this scenario, we tentatively concluded that KOH plays a
role as an external activator through SET pathway. The HO· radical produced by the SET step may be captured by the solvent
or dimerize to form H2O2. However, hydrogen peroxide was not detected directly in the stoichiometric experiment. Adding 10
mol% PPh3 to the mixture of 4 and KOH, 31P NMR spectrum showed the formation of P=O bond during the reduction process
after 48 h. This result shows the possible formation of H2O2 yielded via the dimerization of ·OH (see Supporting Information
for details). Notably, from a perspective of practicality, KOH may be a potential ideal activator for the formation of low-
oxidative-state base-metal species, because KOH has sufficient commercial supply with low price and it is air and moisture-
stable solid which is easy-to-handle and applicable in large-scale processes.
Identification of catalytic active species. The capture and identification of reactive metal hydride species are crucial in the
mechanistic studies of homogeneous hydrogenation. To our delight, in the presence of 10 equivalents of KOH, the isolated
Co(I) complex 4 further reacted with H2 (1~2 bar) in THF-d8 at room temperature, furnishing two new diamagnetic cobalt
complexes in 72% and 24% NMR yield respectively, which were identified as trans-[(H)2CoIII(L1)(BF4)] 5 and [CoI(H)(L1)]
6 (Scheme 3a). Complex 5 was independently prepared via the reaction of isolated Co(I) complex 4 with H2 (1~2 bar) in THF-
d8 at 60 oC over 12h (> 95% conv., Scheme 3b). A single upfield resonance is observed as a quintet at −11.48 ppm (2H, 2JP−H
1
= 23.6 Hz) in the H NMR spectrum, corresponding to two magnetically equivalent hydride ligands having a similar scalar
interaction with the inequivalent phosphorus groups. A similar trans-dihydride cobalt(III) complex was also observed by
Wiedner, Linehan and coworkers in their recent work56. A phosphorus atom might dissociate from the metal before the oxida-
tive addition of dihydrogen and the following rearrangement. Complex 6 was also independently prepared using NaBEt3H as
the hydride source to react with Co(I) complex 4 in acetonitrile-d3 at -38 oC to room temperature (Scheme 3c). A broad signal
at -8.50 ppm (1H) on NMR spectrum was assigned to the Co-H moiety in [CoI(L1)H].
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Scheme 3. Identification of cobalt hydride complexes.
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Both the trans-[(H)2CoIII(L1)(BF4)] and [CoI(H)(L1)] have the potential to reduce polar double bonds. Thus, several stoi-
chiometric experiments were conducted to determine whether the complex 5 or 6 is the active reducing species. Treatment of
5 with one equivalent of trans-cinnamaldehyde in EtOH did not yield the hydrogenation product 3aa (Scheme 4a). However,
the addition of trans-cinnamaldehyde to an EtOH solution of 6 resulted in the formation of 2aa with 98% isolated yield (Scheme
4b). It is revealed that the Co(I) monohydride, rather than trans-Co(III) dihydride, react with polar double bonds. Moreover,
the stoichiometric reaction of 6 with quinoline was also carried out, resulting in formation of hydrogenated product 2ca in 95%
isolated yield (Scheme 4c). It indicates that 6 is also the active reducing species for hydrogenation of N-heteroarenes. The
proton required for equation balance may be taken from the alcoholic solvent.
Scheme 4. Stoichiometric reaction of cobalt hydride complexes with trans-cinnamaldehyde and quinoline.
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Formation of cobalt(I) hydride and cobalt(III) dihydride. The successful identification of 6 as the active reducing species
prompted us to explore the pathway for its formation in the hydrogenation process. It was interesting to observe that nearly
quantitative isolated yield of 2aa was obtained when adding 10 equivalents of KOH to an equimolar mixture of 1aa and 5 while
no reaction of 5 and 1aa occurred without base (Scheme 4a & 4d). This sharp contrast strongly indicates that external base is
able to convert 5 to 6. This transformation from cobalt(III) to cobalt(I) species was assumed to be a deprotonation step. In order
to verify this hypothesis, the reaction of trans-[(H)2CoIII(L1)(BF4)] complex 5 with KOH were conducted. Indeed, complex 5
was deprotonated smoothly in THF-d8 at room temperature over 24 h to give 6 (see Suppporting Information for details). Trans-
dihydride complexes of cobalt are less common in previous literatures56. Taking [Co(dmpe)2(H)2]+ for an example, the for-
mation of trans-dihydride complex is less favored than its cis-counterpart57. However, the macrocyclic P2N2 ring in L1 fixes
the four coordinating phosphorus atoms in a more stable co-planar geometry. Typically, trans-dihydride of metals is formed
from the rearrangement of the corresponding cis-dihydride isomers58.
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It is significant to note that the external base dramatically accelerates the formation of 5. Without base, this process needs
o
harsher conditions (Scheme 3b, 60 C, 12 h). To figure out how the base affects the formation of complex 5, the reaction of
complex 4 with KOH was monitored by 1H and 31P NMR spectroscopy. When the solution of complex 4 was treated with KOH,
the broad peak at 1.82 ppm which was assigned to the coordinating CH3CN shifted to 1.94 ppm. The latter peak was confirmed
to be free acetonitrile (Figure S4). This phenomenon indicated that external base such as KOH benefits the dissociation of
acetonitrile, giving a coordinatively unsaturated 16e- cobalt(I) species which is likely in equilibrium with a 18e- solvent-coor-
dinated cobalt(I) species. When treating the aforementioned solution with molecular hydrogen, complex 5 was formed along
with a little amount of complex 6.
Chemoselectivity and catalytic cycle. In order to explain the excellent chemoselectivity in this chemical transformation, DFT
calculation was performed. The nature of coordinative saturation makes cobalt hydride complexes 6 unable to reduce unfunc-
tionalized olefins. The DFT studies were therefore focused on 1,4- or 1,2-addition of conjugate aldehyde. In the transition states
of stoichiometric reaction of 6 with trans-cinnamaldehyde, the energy barrier of the 1,2-addition was calculated to be 3.53
kcal/mol lower than the 1,4-addition, which suggested an approximate 400:1 chemoselectivity (Table S3). These results were
in the agreement with observed outcomes in the experiment.
To figure out how the [CoI(H)(L1)] complex 6 reacts with aldehydes, the stoichiometric reaction of 6 with 4-F-benzaldehyde
was carried out in THF-d8. This process was monitored by 19F and 31P NMR spectroscopy (Figure S8). It was found that 4-F-
benzaldehyde (19F NMR: -110.3 ppm) was immediately converted to 4-F-benzyl alcohol (19F NMR: -118.2 ppm) at room
temperature. 31P NMR spectroscopy showed the formation of the coordinatively unsaturated 16e- cobalt(I) species when 6 is
completely consumed, which suggested that aldehyde was hydrogenated through a direct hydride transfer process rather than
an inner-sphere hydrogenation mechanism. What’s more, the deuterium-labeling experiment using D2 gas indicates H2 as the
hydrogen donor (see Supporting Information, Section 9).
Based on our experimental observations and the previous study on catalytic CO2 reduction56, we proposed a catalytic cycle
shown in Figure 5. With KOH as one-electron reduction agent, cobalt(II) complex 1 converts to low-oxidation-state cobalt(I)
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counterpart 4. Disassociation of CH3CN occurred to give the coordinatively unsaturated 16e- cobalt(I) species 4, which under-
goes H2 coordination, oxidative-addition and rearrangement to generate the tran-dihydride Co(III) complex 5. This cationic
dihydride species is prone to be deprotonated by an external base, giving a highly reactive cobalt(I) hydride 6. Unsaturated
C=O or C=N bonds are reduced by this intermediate via a hydride transfer step due to strong thermodynamic hydricity of 6.
Although evidences collected in this study were self-consistent and supported the above-mentioned catalytic cycle, other
alternative pathway such as heterolytic split of dihydrogen could still not be completely ruled out.
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Figure 5. Proposed catalytic cycle.
CONCLUSION
In summary, we developed a highly general and efficient method for homogeneous hydrogenation of polar unsaturated com-
pounds including aldehydes, ketones, imines and even challenging N-heteroarenes based on earth abundant metal using mois-
ture and oxygen-insensitive reagents and pre-catalysts. Catalyzed by a Co-P2C-PPh22NPh2 complex, conjugated aldehydes, ketones
and imines and N-heteroarenes were reduced by molecular hydrogen with excellent chemoselectivity over nonpolar C=C bonds.
This catalytic system showed very high activity (TON up to 24000, TOF up to 12000 h-1 for aldehyde; TON up to 1000 for
quinoline) and compatibility with a variety of functionalities. Mechanistic studies were carried out to demonstrate that a Co(I)
hydride complex, rather than a Co(III) dihydride, is the real reducing species. And an outer-sphere mechanism involved direct
hydride transfer was proposed.
Supporting Information
The Supporting Information is available free of charge on the ACS Publications web site.
Experimental procedures and compound characterization data.
Author information
Corresponding Authors
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*wenjl@sustech.edu.cn, *zhangxm@sustech.edu.cn.
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Author contribution
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∥ Ya-Nan Duan and Xiaoyong Du contributed equally to this project.
Competing interests
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The authors declare no competing financial interests.
ACKNOWLEDGMENT
We are grateful to the support from Southern University of Science and Technology, Shenzhen Nobel Prize Scientists Labora-
tory Project (C17783101), Guangdong Natural Science Foundation (2018A030310222) and Special Funds for the Cultivation
of Guangdong College Students’ Scientific and Technological Innovation (pdjhc0022) for financial support.
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