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Journal of the American Chemical Society
Highly Selective Hydrogenation of Aromatic Ketones and Phenols Enabled by Cyclic (Amino)(alkyl)carbene Rhodium Complexes Yu Wei,† Bin Rao,† Xuefeng Cong,† and Xiaoming Zeng*,†,‡ †
Center for Organic Chemistry, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an 710054, China
‡
State Key Laboratory of Elemento-‐organic Chemistry, Nankai University, Tianjin 300071, China
Supporting Information Placeholder ABSTRACT: Air-‐stable Rh complexes ligated by strongly σ-‐ donating cyclic (amino)(alkyl)carbenes (CAACs) show unique catalytic activity for the selective hydrogenation of aromatic ketones and phenols by reducing the aryl groups. The use of CAAC ligands is essential for achieving high selectivity and con-‐ version. This method is characterized by its good compatibility with unsaturated ketones, esters, carboxylic acids, amides, and amino acids, and is scalable without detriment to its efficiency.
yl group in the products, thus offering a straightforward and clean route to cyclohexyl-‐containing ketones and cyclohexa-‐ nones, which are fundamental feedstock materials and widely used as key precursors to industrially important molecules such 19 as caprolactam and adipic acid.
Scheme 1. Selective Hydrogenation of Aromatic Ketones and Phenols (a) The selective hydrogenation of aromatic ketones (two pathways)
Selective hydrogenation is one of the most powerful and useful reactions because of its synthetic significance in the creation of pharmaceuticals, materials, and fundamental feedstock chemi-‐ 1,2 cals. Despite considerable achievements, chemoselectivity has long been a prominent obstacle when several unsaturated scaf-‐ 3 folds are present in the same substrates. Compared with polar carbonyls, the aromatic hydrocarbons are difficult substrates for hydrogenation, probably because of the stability caused by aro-‐ 4,5 maticity. As a result, the hydrogenation of aromatic ketones often leads to aryl-‐containing alcohol products via a preferential 6 carbonyl reduction (Scheme 1a, path a). In contrast, switching the selectivity to realize arene hydrogenation while retaining an easily reducible carbonyl is more challenging, and has not been achieved with structurally well-‐defined homogeneous catalysts 7 to date (Scheme 1a, path b). Another key problem is inhibiting the reduction of the resulting ketones to alcohols or dehydrox-‐ ylated products (e.g., 4a and 5a). Especially for naturally abun-‐ dant phenols, efficient strategies for reducing them to cyclohex-‐ 8,9 anones by avoiding a carbonyl reduction are rare (Scheme 1b). From both sustainable and synthetic points of view, developing a general protocol to address these selectivity challenges would help advance clean chemical syntheses. Recently, there has been significant progress in the rational design of effective organometallic catalysts using σ-‐donating N-‐ 10,11 heterocyclic carbenes (NHCs), and a number of elegant ex-‐ amples of NHC ligand-‐promoted hydrogenation have been re-‐ 12 13 14 15 ported by Glorius, Stephan, Crabtree, and others. Differ-‐ ing from classic NHCs, cyclic (amino)(alkyl)carbenes (CAACs) show an enhanced nucleophilicity because of a σ-‐donating alkyl substituent, which was discovered by Bertrand and has received 16,17 increasing interest recently. However, the ligand effect of 18 CAACs in organometallic catalysis has rarely been studied. Herein we report the first CAAC ligand-‐enabled, highly selective hydrogenation of aromatic ketones and phenols with rhodium (Scheme 1). This method retains a synthetically valuable carbon-‐
Et
5a H2
Et
ketone hydrogenation path a
O
Et
OH
cat. Ru, Ir, Pd, Rh, Fe, FLP...
H2
H2
Et
O
1a
(CAAC)Rh(COD)Cl CF3CH2OH, r.t. arene hydrogenation path b
X
Et
4a
3a R1
N (b) The selective hydrogenation of phenols to cyclohexanones OH
H2
CF3CH2OH/H2O phenol hydrogenation
Cl
R2 Rh COD
CAAC-Rh
OH
O
(CAAC)Rh(COD)Cl
6a
OH
2a
X
isomerization A
OH
7a
8a
To ensure that the arene hydrogenation occurs preferentially over that of ketones, a suitable catalyst that allows interaction with the aryl group via a π-‐coordination is required. We postu-‐ lated that electron-‐rich CAAC ligands, with their strong σ-‐ electron donation to the metal center, might enhance the inter-‐ action of the metal with the aryl by the back-‐donation of elec-‐ tron density from the filled d orbitals of the metal into the unoc-‐ 12b cupied π*aryl anti-‐bonding orbital. This may favor the arene hydrogenation with H2. Meanwhile, the electron-‐rich metal may 20 be expected to show rather low oxophilicity. Compared with other transition metals, rhodium shows high reactivity towards 1 arene hydrogenation. At the outset, the impact of Rh complex-‐ es on the selective hydrogenation of propiophenone was evalu-‐ ated (Table 1). In the presence of Wilkinson’s catalyst, a trace amount of the aryl-‐reduced product 3a was detected by GC-‐MS analysis (entry 2). Similar results were obtained using [Rh(cp*)Cl2]2 and RhCl3•H2O (entries 3 and 4). A complex of [Rh(COD)Cl]2 improves the reaction to give 3a in 29% yield, but with various by-‐products of 2a, 4a, and 5a (entry 5).
Table 1. The Influence of Rhodium Complexes on the Aryl-‐ a,b Selective Hydrogenation of Propiophenone
ACS Paragon Plus Environment
Journal of the American Chemical Society O
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
O
Et
H2 (0.5 Mpa) rhodium complex (3 mol %)
Et
Et
3a
2a
+
OH
CF3CH2OH, 4 Å MS r.t., 24 h
1a
OH
Et
Et 5a
4a
Rhodium complex
Yield (3a)
1
none
nd
nd
c
nd
c
nd
2
Rh(PPh3)3Cl
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Journal of the American Chemical Society
Highly Selective Hydrogenation of Aromatic Ketones and Phenols Enabled by Cyclic (Amino)(alkyl)carbene Rhodium Complexes Yu Wei,† Bin Rao,† Xuefeng Cong,† and Xiaoming Zeng*,†,‡ †
Center for Organic Chemistry, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an 710054, China
‡
State Key Laboratory of Elemento-‐organic Chemistry, Nankai University, Tianjin 300071, China
Supporting Information Placeholder ABSTRACT: Air-‐stable Rh complexes ligated by strongly σ-‐ donating cyclic (amino)(alkyl)carbenes (CAACs) show unique catalytic activity for the selective hydrogenation of aromatic ketones and phenols by reducing the aryl groups. The use of CAAC ligands is essential for achieving high selectivity and con-‐ version. This method is characterized by its good compatibility with unsaturated ketones, esters, carboxylic acids, amides, and amino acids, and is scalable without detriment to its efficiency.
yl group in the products, thus offering a straightforward and clean route to cyclohexyl-‐containing ketones and cyclohexa-‐ nones, which are fundamental feedstock materials and widely used as key precursors to industrially important molecules such 19 as caprolactam and adipic acid.
Scheme 1. Selective Hydrogenation of Aromatic Ketones and Phenols (a) The selective hydrogenation of aromatic ketones (two pathways)
Selective hydrogenation is one of the most powerful and useful reactions because of its synthetic significance in the creation of pharmaceuticals, materials, and fundamental feedstock chemi-‐ 1,2 cals. Despite considerable achievements, chemoselectivity has long been a prominent obstacle when several unsaturated scaf-‐ 3 folds are present in the same substrates. Compared with polar carbonyls, the aromatic hydrocarbons are difficult substrates for hydrogenation, probably because of the stability caused by aro-‐ 4,5 maticity. As a result, the hydrogenation of aromatic ketones often leads to aryl-‐containing alcohol products via a preferential 6 carbonyl reduction (Scheme 1a, path a). In contrast, switching the selectivity to realize arene hydrogenation while retaining an easily reducible carbonyl is more challenging, and has not been achieved with structurally well-‐defined homogeneous catalysts 7 to date (Scheme 1a, path b). Another key problem is inhibiting the reduction of the resulting ketones to alcohols or dehydrox-‐ ylated products (e.g., 4a and 5a). Especially for naturally abun-‐ dant phenols, efficient strategies for reducing them to cyclohex-‐ 8,9 anones by avoiding a carbonyl reduction are rare (Scheme 1b). From both sustainable and synthetic points of view, developing a general protocol to address these selectivity challenges would help advance clean chemical syntheses. Recently, there has been significant progress in the rational design of effective organometallic catalysts using σ-‐donating N-‐ 10,11 heterocyclic carbenes (NHCs), and a number of elegant ex-‐ amples of NHC ligand-‐promoted hydrogenation have been re-‐ 12 13 14 15 ported by Glorius, Stephan, Crabtree, and others. Differ-‐ ing from classic NHCs, cyclic (amino)(alkyl)carbenes (CAACs) show an enhanced nucleophilicity because of a σ-‐donating alkyl substituent, which was discovered by Bertrand and has received 16,17 increasing interest recently. However, the ligand effect of 18 CAACs in organometallic catalysis has rarely been studied. Herein we report the first CAAC ligand-‐enabled, highly selective hydrogenation of aromatic ketones and phenols with rhodium (Scheme 1). This method retains a synthetically valuable carbon-‐
Et
5a H2
Et
ketone hydrogenation path a
O
Et
OH
cat. Ru, Ir, Pd, Rh, Fe, FLP...
H2
H2
Et
O
1a
(CAAC)Rh(COD)Cl CF3CH2OH, r.t. arene hydrogenation path b
X
Et
4a
3a R1
N (b) The selective hydrogenation of phenols to cyclohexanones OH
H2
CF3CH2OH/H2O phenol hydrogenation
Cl
R2 Rh COD
CAAC-Rh
OH
O
(CAAC)Rh(COD)Cl
6a
OH
2a
X
isomerization A
OH
7a
8a
To ensure that the arene hydrogenation occurs preferentially over that of ketones, a suitable catalyst that allows interaction with the aryl group via a π-‐coordination is required. We postu-‐ lated that electron-‐rich CAAC ligands, with their strong σ-‐ electron donation to the metal center, might enhance the inter-‐ action of the metal with the aryl by the back-‐donation of elec-‐ tron density from the filled d orbitals of the metal into the unoc-‐ 12b cupied π*aryl anti-‐bonding orbital. This may favor the arene hydrogenation with H2. Meanwhile, the electron-‐rich metal may 20 be expected to show rather low oxophilicity. Compared with other transition metals, rhodium shows high reactivity towards 1 arene hydrogenation. At the outset, the impact of Rh complex-‐ es on the selective hydrogenation of propiophenone was evalu-‐ ated (Table 1). In the presence of Wilkinson’s catalyst, a trace amount of the aryl-‐reduced product 3a was detected by GC-‐MS analysis (entry 2). Similar results were obtained using [Rh(cp*)Cl2]2 and RhCl3•H2O (entries 3 and 4). A complex of [Rh(COD)Cl]2 improves the reaction to give 3a in 29% yield, but with various by-‐products of 2a, 4a, and 5a (entry 5).
Table 1. The Influence of Rhodium Complexes on the Aryl-‐ a,b Selective Hydrogenation of Propiophenone
ACS Paragon Plus Environment
Journal of the American Chemical Society O
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
O
Et
H2 (0.5 Mpa) rhodium complex (3 mol %)
Et
Et
3a
2a
+
OH
CF3CH2OH, 4 Å MS r.t., 24 h
1a
OH
Et
Et 5a
4a
Rhodium complex
Yield (3a)
1
none
nd
nd
c
nd
c
nd
2
Rh(PPh3)3Cl
