2
Zinc-Catalyzed Reductions of Unsaturated Compounds

Yuehui Li, Kathrin Junge and Matthias Beller

2.1 Introduction

Catalytic reductions represent an important class of synthetic methodologies and have attracted the long-lasting interest of academic and industrial researchers in the last few decades [1]. In general, saturated compounds are formed in a straightforward manner by the addition of hydrogen to the unsaturated substrates. Specifically, alcohols, alkanes, and amines are produced via reduction of C=C, C=O, and C=N bonds. With the aid of catalysts, high efficiency and selectivity can be obtained in the presence of a suitable reductant. In this regard, the activation of the reducing reagent and the control of chemo-, regio-, and stereoselectivity by appropriate transition metal catalysts are essential. To date, most reduction methodologies were developed using precious metals such as Ru, Rh, Ir, Pt, and Pd. Owing to economic and ecologic constraints, nonprecious metals such as Ni, Cu, Fe, and Zn come more into the limelight of catalysis. Zinc, as an essential mineral and constituent of enzymes, is of fundamental biochemical importance for plants, animals, and humans. In fact, the redox properties of Zn are known for a long time, although research on Zn-catalyzed reductions has been scarce [2]. In this chapter, we summarize the use of Zn-based homogeneous catalysts in hydrogenations, transfer hydrogenations, and hydrosilylation reactions of C=O and C=N bonds. In addition, a few examples of related reductions of olefins and sulfoxides are highlighted.

2.2 Hydrosilylation of Unsaturated Compounds

Already in the 1960s and 1970s efforts were undertaken to utilize cheap and benign zinc salts (Zn, 0.07 ? mol-1) for hydrosilylation of unsaturated compounds [1, 2]. However, more recently, this topic has been rediscovered and significant improvements regarding more active and highly selective catalysts for the reduction of various functionalized substrates using silanes were reported (Scheme 2.1).

Scheme 2.1 Catalytic efficient hydrosilylation of unsaturated compounds (FG = functional group).

2.2.1 Nonchiral Hydrosilylation of Carbonyl Bonds

As early as in the 1960s, Calas et al. [3] investigated the use of ZnCl2 to promote the reduction of acetals (to ethers), nitriles (to N-silyl imines or amines), amides or imidates (to amines), and lactones (to silyl ethers) with trialkylsilanes at elevated temperatures. It was proposed that typical Lewis-acid-catalyzed hydrosilylations took place. In 1978, Lapkin et al. reported the chemoselective hydrosilylation of a- and ß-ketoesters. In the presence of 3.7 mol% of ZnCl2, moderate to good yields were obtained using 1 equiv of triethylsilane (Scheme 2.2) [4].

Scheme 2.2 Zinc-catalyzed hydrosilylation of a- and ß-ketoesters.

Important works on zinc-catalyzed hydrosilylation of ketones were reported in 1987 by the group of Lukevics and by Mimoun in the late 1990s [5, 6]. Both systems focused on asymmetric reductions and the details are discussed in Section 2.2.2. Based on this initial work in the field of asymmetric hydrosilylations, several research groups became interested in the investigation of the reaction mechanism and the development of new ligands for more efficient zinc catalysis. For example, in 1999 Mimoun reported the Zn(2-ethylhexanoate)2-catalyzed hydrosilylation of aldehydes, ketones, epoxides, and esters using cheap PMHS (polymethylhydrosiloxane) as the reductant in the presence of a catalytic amount of NaBH4 [7]. Very high yields were obtained for almost all substrates. It was found that the use of this specific zinc dialkoxide is critical for the reactivity (e.g., almost no reaction occurs when using zinc(II) acetate). Meanwhile, an excellent functional group tolerance toward olefins was observed. Thus, triolein (glyceryl trioleate) was reduced almost quantitatively to give the corresponding oleyl alcohol. Furthermore, it was proposed that the interchange between zinc hydride and zinc alkoxide is important to activate PMHS to pentacoordinated hydrosilicates.

In 2003, Carpentier et al. reported the zinc-catalyzed hydrosilylation of ketones and imines in a methanol-toluene solvent mixture applying PMHS as the reductant. In the presence of 2 mol% precatalyst good to excellent yields (76-99%) were obtained for both aromatic and aliphatic ketones. The crucial role of the protic solvent for achieving high reactivity was discussed [8]. Later in 2010, the Driess group published the use of preformed zinc-O,S,S´-ligand precatalysts for the efficient hydrosilylation of ketones. TOF up to 970 h-1 were obtained by applying complex 1 (0.1 mol%) (Scheme 2.3a). The catalyst was made via direct acid-base reaction of the ligand with dimethylzinc in a 1 : 1 molar ratio followed by the coordination with a diamine auxiliary ligand (e.g., tetramethylethylenediamine (TMEDA)). To understand the reactivity in more detail, NMR experiments were also carried out [9]. Recently, Enthaler et al. [10] reported the application of versatile formamidines as ligands for the zinc-catalyzed hydrosilylation of ketones. A strong ligand acceleration effect was observed for the combination of L1 and ZnEt2 (Scheme 2.3b). It was discovered that ZnEt2/L1 (R1 = Me, R2 = Me, R3 = 2,4,6-Me3C6H2) showed the best reactivity (yields 18-87%). For a number of aromatic and aliphatic ketones, excellent yields were obtained (76-98% isolated yield). However, ortho-substituted aromatic substrates (e.g., 2,6-dimethylacetophenone and its derivatives) showed no reactivity. Mechanistically, it is interesting that the hydride character of the silanes (determined by NMR spectroscopy) showed no correlation with the reactivity. The same group also reported modified zinc precatalysts for the hydrosilylation of ketones (Scheme 2.3c) based on different phenol ligands L2 [11]. Compared to the former method, similar reactivities and a broad functional group tolerance were achieved. Notably, the proposed mechanism suggested coordination of the zinc complex with the ketone substrate to activate the substrate molecule. Following this, the hydride of the silane was directly transferred to the carbonyl group [5].

Scheme 2.3 (a-c) Zinc-catalyzed hydrosilylation of ketones with different ligand classes.

Notably, a remarkable ligand-free approach was presented by Konod, Aoyama, and coworkers [12] Interestingly, a strong solvent effect was observed in the Zn(OAc)2-catalyzed hydrosilylation of ketones. In the presence of 2 equiv of PhSiH3 at room temperature, under the same conditions, the solvent N,N-dimethylformamide (DMF) gave quantitative yields, although there are only traces of the product in other solvents, such as acetonitrile, tetrahydrofuran (THF), 1,4-dioxane, ethyl acetate, toluene, and methanol.

Interestingly, when aldehydes are used as substrates, silyl ethers or symmetric ethers can be obtained through zinc-catalyzed hydrosilylation reactions. By switching the silane from 1,1,3.3-tetramethyldisiloxane (TMDS) to Et3SiH, silyl ethers were obtained instead of symmetric ethers for the reduction of aromatic aldehydes. In the case of aliphatic aldehydes, the symmetric ethers were produced in good yields with the combination of Zn(OTf)2 and triethylsilane. After control experiments, the reaction pathway was proposed to proceed through the formation of the silyl ether as the key intermediate followed by its attack on the activated aldehyde to form the silylated hemiacetal. After a second reduction with another silane molecule, the corresponding symmetric ether was obtained. Accordingly, when the benzene ring of the substrate is electron deficient, the subsequent addition step cannot happen with the formation of silyl ethers as the major products (Scheme 2.4) [13].

Scheme 2.4 Zinc-catalyzed hydrosilylation of aldehydes to ethers.

The selective 1,2-reduction of a,ß-unsaturated ketones to olefins represents an important chemical transformation in organic chemistry. This task can be achieved by zinc-catalyzed hydrosilylation, which was reported by Mimoun et al. [6, 7] in 1990s. This topic was recently investigated in detail by Lai and coworkers [14]. Among the different tested zinc salts and silanes, ZnCl2 and (MeO)3SiH showed the best reactivity for all substrates. Quantitative yield of the desired product can be obtained after 5 min. However, isomerization of the C=C bond occurred (Scheme 2.5).

Scheme 2.5 Zinc-catalyzed hydrosilylation of a,ß-unsaturated ketones.

[Tris(2-pyridylthio)methyl]zinc hydride {[?3-Tptm]Zn, 2} was used by the Parkin group as catalyst for hydrolysis of Si-H bonds (see Chapter 4). In addition, complex 2 can be an efficient catalyst for the hydrosilylation of ketones and carbon dioxide (Scheme 2.6). For the reduction of acetaldehyde and acetone catalyst, TOF up to 996 h-1 was obtained. The reduction of CO2 to formic acid is an actual topic in carbon dioxide chemistry [15]. Under neat conditions, a TOF of 4.2 h-1 was obtained using 0.25 mol% of {[?4-Tptm]Zn(OSiMe3), 3} in the presence of 1 equiv of triethoxysilane, producing the...