Ligand Platforms in Homogenous Catalytic Reactions with Metals: Practice and Applications for Green Organic Transformations

By Ryohei Yamaguchi and Ken-ichi Fujita

Serving as a user's manual for synthetic organic and catalytic chemists, this book guides chemists in the design and choice of ligands to catalyze organic reactions and apply the results for more efficient, green, and practical synthesis.

• Focuses on the role of ligands in metal complexes that catalyze green organic transformations: a hot topic in the area of organic synthesis and green chemistry
• Offers a comprehensive resource to help readers design and choose ligands and understand selectivity/reactivity characteristics
• Addresses a gap by taking novel ligand approaches and including up-to-date discussion on hydrogen transfers and reactions
• Presents important industrial perspective and provides rational explanations of ligand effects, impacts, and novelty

• Language: English
• Publisher: Wiley
• Release date: Oct 15, 2014
• ISBN: 9781118943090

Book preview

Part I

N-Heterocyclic Carbene Ligands in Transition Metal Catalyzed Hydrogen Transfer and Dehydrogenative Reactions

1

Oxidation and Hydrogenation Reactions Catalyzed by Transition Metal Complexes Bearing N-Heterocyclic Carbene Ligands

1.1 Introduction

The aim of this chapter is to survey the oxidative reactions of alcohols based on hydrogen transfer as well as dehydrogenation and hydrogenation reactions catalyzed by transition metal complexes having N-heterocyclic carbene (NHC) ligands. Herein, catalytic reactions useful for environmentally benign organic synthesis will be classified into four types: (i) oxidation of alcohols based on hydrogen transfer, (ii) oxidation of alcohols based on dehydrogenation, (iii) hydrogenation reactions of carbon–heteroatom unsaturated bond, and (iv) other related hydrogenative reactions. This chapter is not exhaustive on the catalytic chemistry of NHC complexes of transition metals. There are a number of good review articles on such subjects [1].

1.2 Oxidation of Alcohols Based on Hydrogen Transfer

1.2.1 Ruthenium Complex with NHC Ligand

The ruthenium complex 1 bearing an NHC ligand with mesityl substituent was found to undergo a facile dehydrogenative reaction in the presence of acetone to afford a cyclometalated complex 1′ [2]. The original complex 1 can be restored by the reaction of the complex 1′ with 2-propanol, enabling a reversible transformation system between 1 and 1′ (Scheme 1.1). On the basis of this reversible reaction associated with hydrogen transfer, a catalytic system for the oxidation of alcohols catalyzed by 1 using acetone as a hydrogen acceptor in NMR scale has been investigated (Scheme 1.2). When the reaction of 1-phenylethanol catalyzed by 1 (2 mol%) was performed in C6D6 at 50 °C for 12 h using 5 equiv of acetone as a hydrogen acceptor, acetophenone was formed in the yield of 88%. Various secondary alcohols were also converted to the corresponding ketones although the yield depended on equilibrium position.

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SCHEME 1.1

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SCHEME 1.2

1.2.2 Iridium Complex with NHC Ligand

The dicationic iridium complex 2 bearing an NHC ligand has been synthesized, and its high activity for the oxidation of alcohols using acetone as a hydrogen acceptor based on hydrogen transfer process (Oppenauer-type oxidation [3]) has been revealed [4]. Results of the oxidation of secondary alcohols into ketones catalyzed by the NHC iridium complex 2 are summarized in Table 1.1. For example, the reaction of 1-phenylethanol in the presence of 2 (0.1 mol%) and K2CO3 (0.1 mol%) in acetone gave acetophenone in excellent yield (Entry 1). The highest turnover number up to 6640 was achieved for the oxidation of cyclopentanol (Entry 6).

Table 1.1 Oxidation of secondary alcohols catalyzed by 2.

aCatalyst loading was 0.0125 mol%.

Results of the oxidation of primary alcohols catalyzed by 2 are summarized in Table 1.2 [4]. While larger quantities of the catalyst (0.5 mol%) were required, the oxidation of primary alcohols into aldehydes proceeded selectively in moderate to excellent yields.

Table 1.2 Oxidation of primary alcohols catalyzed by 2.

A possible mechanism for the Oppenauer-type oxidation of alcohols is shown in Scheme 1.3 [4]. Firstly, an iridium alkoxo species is generated from 2 and an alcohol mediated with a base. Then, β-hydrogen elimination occurs to yield a carbonyl product and a hydrido iridium species. Finally, the insertion of acetone into iridium hydride bond followed by the exchange of the alkoxo moiety proceeds to regenerate the iridium alkoxo species.

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SCHEME 1.3

The iridium complex 3 bearing a dimethylamino-tethered cyclopentadienyl as well as NHC ligand has been found to be a good catalyst for Oppenauer-type oxidation of various alcohols [5]. Owing to the basic dimethylamino moiety in the ligand, the reaction catalyzed by 3 can be conducted in the absence of an additional base. Compared to the dicationic catalyst 2, the catalytic system composed of 3 and AgOTf exhibited a higher activity (Scheme 1.4).

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SCHEME 1.4

The NHC iridium complex 4 has been utilized as a good catalyst for the racemization of secondary alcohols, which is incorporated with enzyme catalyst for kinetic resolution to construct an efficient system for the dynamic kinetic resolution. As shown in Scheme 1.5, the reaction of racemic 1-phenylethanol with isopropenyl acetate in the presence of 4 (0.1 mol%) and Novozyme 435 at 70 °C for 8 h gave an acetyl ester in 95% yield with 97% enantiomeric excess (ee) [6].

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SCHEME 1.5

1.2.3 Palladium Complex with NHC Ligand

The palladium complex 5 bearing an NHC ligand and two acetate ligands has been reported to catalyze the aerobic oxidation of alcohols (Table 1.3) [7]. For example, the reaction of 1-phenylethanol in the presence of NHC palladium complex 5 (0.5 mol%) and acetic acid (2 mol%) in toluene under an oxygen atmosphere for 5 h gave acetophenone in the yield of 98% (Entry 1). Various types of alcohols could be oxidized by this system.

Table 1.3 Aerobic oxidation of alcohols catalyzed by 5.

The mechanism for the oxidation catalyzed by 5 is illustrated in Scheme 1.6 [7]. After the loss of H2O from 5, an alcohol coordinates to the metal center. Then, an intramolecular deprotonation releasing acetic acid occurs to generate a palladium alkoxide species, which undergoes β-hydrogen elimination to yield the carbonyl product and a hydrido palladium species. Reductive elimination of acetic acid proceeds to give zerovalent palladium, which is subject to oxidized by oxygen giving peroxo palladium species. Finally, protonation by 2 equiv of acetic acid occurs to regenerate the NHC palladium diacetate accompanying the elimination of H2O2.

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SCHEME 1.6

An efficient system for the oxidative kinetic resolution of secondary alcohols has been developed using an NHC palladium complex and (−)-sparteine as catalyst [8]. As shown in Scheme 1.7, the reaction of racemic 1-phenylethanol in the presence of the dimeric NHC palladium complex 6 (1.5 mol%) and (−)-sparteine (15 mol%) under oxygen atmosphere in dichloroethane at 65 °C for 20 h gave an (S)-isomer of 1-phenylethanol (96% ee) at the conversion of 65%.

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SCHEME 1.7

1.3 Oxidation of Alcohols Based on Dehydrogenation

1.3.1 Ruthenium Complex with NHC Ligand

Dehydrogenative oxidation of alcohols is important for the production of synthetically useful aldehydes and ketones from readily available alcohols with high atom efficiency without the use of any oxidant [9]. The ruthenium complexes 7–10 bearing an NHC ligand have been applied as catalysts for such a reaction [10]. As shown in Table 1.4, some arene ruthenium complexes bearing NHC ligand exhibited catalytic activity for the dehydrogenative oxidation of benzyl alcohol into benzaldehyde. Among ruthenium complexes 7–10, the complex 7 having a triazolylidene-based NHC and p-cymene ligand showed the highest activity (Entry 1). The complex 10 having imidazolylidene-based NHC ligand was slightly less active than 7 (Entry 4), probably because of the difference of electronic properties of NHC ligands.

Table 1.4 Catalyst screening in the oxidation of benzyl alcohol.

Results of the dehydrogenative oxidation of a variety of alcohols catalyzed by the ruthenium complex 7 are summarized in Table 1.5 [10]. Both primary and secondary benzylic alcohols were oxidized into benzaldehydes and acetophenone, respectively. Electron-withdrawing substituents such as nitro or chloro group reduced the activity of the catalyst. By this catalytic system, aliphatic alcohols could not be oxidized.

Table 1.5 Dehydrogenative oxidation of various secondary alcohols catalyzed by 7.

1.3.2 Iridium Complex with NHC Ligand

Catalytic activity of the iridium complex 11 bearing a pentamethylcyclopentadienyl (Cp*) and imidazolylidene-based NHC ligands in dehydrogenative oxidation of alcohols has been reported (Scheme 1.8) [11]. When the reaction of 1-phenylethanol was carried out in the presence of the NHC iridium complex 11 (5 mol%) and Cs2CO3 (20 mol%) at 110 °C for 24 h, acetophenone was obtained in the yield of 70%. Similar reaction using benzyl alcohol as a substrate gave benzaldehyde in 50% yield.

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SCHEME 1.8

1.4 Hydrogenation and Transfer Hydrogenation of Carbon–Heteroatom Unsaturated Bonds

1.4.1 Ruthenium Complex with NHC Ligand

The water-soluble ruthenium complex 12 bearing an imidazolylidene-based NHC and 1,3,5-triaza-7-phosphaadamantane ligands has been synthesized, and its catalytic application to the hydrogenation of carbonyl substrates in aqueous media has been studied (Scheme 1.9) [12]. Hydrogenation of acetone and propanal catalyzed by the NHC ruthenium complex 12 (0.7 mol%) in water (pH 6.9) at 80 °C under 10 atm of H2 gave acetone and 1-propanol in high yields, respectively.

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SCHEME 1.9

The ruthenium complex 13 bearing two NHC ligands exhibited high catalytic performance for the hydrogenation of acetophenone [13]. When the reaction of acetophenone catalyzed by 13 (0.4 mol%) was carried out in 2-propanol at 75 °C under H2 (10 atm), 1-phenylethanol was obtained in excellent yield (Scheme 1.10).

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SCHEME 1.10

The NHC ruthenium catalyst generated in situ from [Ru(cod)(2-methallyl)2] 14, imidazolium salt 15, and KOtBu effectively catalyzes the hydrogenation of carbon–nitrogen triple bond of nitrile (Table 1.6) [14]. For example, the reaction of benzonitrile in the presence of 14 (0.5 mol%), 15 (0.5 mol%), and KOtBu (10 mol%) in toluene at 40 °C under 35 bar of hydrogen for 6 h gave benzylamine in almost quantitative yield (Entry 1). A variety of aromatic nitriles were also converted into primary amines in good to excellent yields (Entries 2–6).

Table 1.6 Hydrogenation of nitriles to primary amines catalyzed by 14 and 15.

The arene ruthenium complex 16 with amine-tethered NHC has been prepared, and its catalytic activity toward transfer hydrogenation of aromatic ketones has been revealed (Table 1.7) [15]. When the reaction of acetophenone was conducted in the presence of 16 (1 mol%), AgOTf (1 mol%), and KOtBu (5 mol%) in 2-propanol at 80 °C for 12 h, 1-phenylethanol was formed almost quantitatively (Entry 1). Substituted acetophenone derivatives were also converted into secondary alcohols in excellent yields.

Table 1.7 Transfer hydrogenation of aromatic ketones catalyzed by 16.

The ruthenium complex 17 bearing an orthometalated NHC ligand has been found to be a highly efficient catalyst for the transfer hydrogenation of ketones [16]. Results are summarized in Table 1.8. Various kinds of ketones with or without functional groups were converted into the corresponding secondary alcohols with high turnover numbers using a very small amount of 17 (0.05 mol%). It should be also noted that the reduction of 5-hexene-2-one proceeded selectively at the carbonyl group without hydrogenation or isomerization of the carbon–carbon double bond (Entry 7).

Table 1.8 Transfer hydrogenation of ketones catalyzed by 17.

Other NHC ruthenium complex-catalyzed transfer hydrogenation reactions of carbon–heteroatom unsaturated bond have been known [17].

1.4.2 Rhodium Complex with NHC Ligand

The rhodium complex 18 bearing a chelating bis-NHC ligand showed high catalytic performance in the transfer hydrogenation of ketones and imines using 2-propanol as a hydrogen donor [18]. Results are summarized in Table 1.9. When the reaction of acetophenone was performed in the presence of NHC rhodium complex 18 (0.1 mol%) and KOH (50 mol%) in 2-propanol under reflux for 10 h, 1-phenylethanol was obtained in quantitative yield (Entry 1). Both aromatic and aliphatic ketones were also converted to the corresponding secondary alcohols (Entries 1–4). The complex 18 also catalyzed the transfer hydrogenation of imines to the corresponding amines (Entries 5 and 6).

Table 1.9 Transfer hydrogenation of ketones and imines catalyzed by 18.

Other NHC rhodium complex-catalyzed transfer hydrogenation reactions of carbon–heteroatom unsaturated bond have been also reported [19].

1.4.3 Iridium Complex with NHC Ligand

The cationic iridium complex 19 bearing an imidazolylidene-based NHC ligand exhibits very high catalytic performance in the transfer hydrogenation [20]. As shown in Table 1.10, ketones, alkenes, and nitro compounds were effectively converted to alcohols, alkanes, and amines by 0.025 mol% of NHC iridium complex 19 using 2-propanol as a hydrogen donor.

Table 1.10 Transfer hydrogenation of ketones, alkenes, and nitro compounds catalyzed by 19.

Selective transfer hydrogenation of bifunctional substrate (3-acetylbenzaldehyde) has been accomplished by the employment of the cationic iridium complex 20 with NHC and phosphine ligands (Scheme 1.11) [21].

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SCHEME 1.11

The iridium complex 21 bearing a hemilabile O-donor-functionalized NHC ligand has been prepared, and it was found to be a good catalyst for the transfer hydrogenation [22]. Transfer hydrogenation of various kinds of substrates including ketones, aldehydes, alkenes, and imines was catalyzed by the cationic iridium complex 21 using 2-propanol as a hydrogen donor (Table 1.11). A positive effect of the methoxy group in the NHC ligand on the catalytic activity would be due to the facilitation of the β-hydrogen elimination step in the catalytic process.

Table 1.11 Transfer hydrogenation of various substrates catalyzed by 21.

Transfer hydrogenation of ketones, aldehydes, and imines has been achieved at room temperature by the employment of the iridium complex 22 bearing Cp* and NHC ligands (Table 1.12) [23]. For example, the reaction of 2-butanone in the presence of the NHC iridium complex 22 (2 mol%) and AgOTf (6 mol%) in 2-propanol at room temperature for 2 h gave 2-butanol quantitatively (Entry 1). The reaction catalyzed by 22 proceeded in a short time without using