Asymmetric Hydrosilylation of Ketones and Imines

Iridium complexes are known to be generally less active in hydrosilylation reactions when compared to rhodium derivatives, although iridium-based catalysts with bonded chiral carbene ligands have been used successfully in the synthesis of chiral alcohols and amines via hydrosilylation/protodesilylation of ketones [46-52] and imines [53-55], The iridium-catalyzed reaction of acetophenone derivatives with organosubstituted silanes often gives two products (Equation 14.3)  

Neutral iridium(I) complexes [Ir(Cl)(cod)(L)] [46] consisting of the chiral carbene ligands LI and L2 have been shown as active catalysts for the asymmetric hydrosi- 

Iridium(l) precursors [lr(cod)(L)] with bidentate N-heterocyclic carbene ligands L3 appeared slightly less active in the hydrosilylation of acetophenone with diphe-nylsilane than did the similar rhodium complexes, giving respectively yields of 85% of I and 15% of II for the Pr substituent, and 83% of I and 17% of II for the benzyl moiety, after 2 h reaction at room temperature [47]. However, when carbene ligands of type L3 were used a significant increase in the ee-value of the sec-phenethyl alcohol R isomer of up to 60% was observed. 

Other carbene iridium complexes (Cl, C2) were also applied as catalysts of this reaction, but their catalyhc achvity was very low (only 10% yields of I for Cl and 58% for C2 were obtained) [48]. 

Catalyhc systems based on the commonly used iridium precursor [ Ir(g-Cl)(cod) 2] and diferrocenyl dihalcogenides of L4 and L5 type were also studied in the asymmetric hydrosilylahon of acetophenone, giving a relahvely high yield of sec-phenetyl alcohol silyl ether (I) and a moderate ee of one stereoisomer [49]. 

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While it is beyond the scope of this chapter to cover the asymmetric hydrosilylation of ketones and imines in any detail, a number of the more catalytically active ML combinations will be mentioned here. A full review of the area has recently appeared.138 Asymmetric hydrosilylation of carbonyl groups is usually performed with rhodium or titanium catalysts bearing chelating N- or P-based ligands. Representative results for some of the most active Rh/L combinations (Scheme 32) for addition of Si H to acetophenone are given in Table 11. 

ASYMMETRIC HYDROSILYLATION OF KETONES AND IMINES WITH RH AND RU CATALYSTS... 

Recent advances in the asymmetric hydrosilylation of ketones and imines have been reviewed.276... 

Diselenides as Chiral Ligands for Asymmetric Hydrosilylation of Ketones and Imines... 

In 1999 [22] and 2001 [23], Matsumura and co-workers reported the first examples of stereoselective hydrosilylation with HSiCla and (5)-proline derivatives as effective activators. These works can be considered as milestones for the asymmetric reduction of ketones and imines using HSiCla as reducing agent and paved the road to the synthesis of other related systems. Since then, considerable efforts have been devoted to the development of efficient catalysts for the reduction of carbon-nitrogen double bonds, and remarkable progress has been made. 

Asymmetric hydrosilylation of ketones and ketoimines has been demonstrated in the absence of transition metal catalysts. Using catalytic amounts of chiral-alkoxide Lewis bases such as binaphthol (BINOL), Kagan was able to facilitate the asymmetric reduction of ketones (eq 19). This process is believed to arise from activation of the triethoxysilane by mono-alkoxide addition to give an activated pentavalent intermediate, which can undergo coordination of an aldehyde. This highly ordered hexacoordinate transition state directs reduction in an asymmetric manner, with subsequent catalyst regeneration. Brook was able to facilitate a similar tactic for asymmetric reduction by employing histidine as a bi-dentate Lewis base activator of triethoxysilane. A similar chiral lithium-alkoxide-catalyzed asymmetric reduction of imines was demonstrated by Hosomi with the di-lithio salt of BINOL and trimethoxysilane. ... 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Optically active alcohols, amines, and alkanes can be prepared by the metal catalyzed asymmetric hydrosilylation of ketones, imines, and olefins [77,94,95]. Several catalytic systems have been successfully demonstrated, such as the asymmetric silylation of aryl ketones with rhodium and Pybox ligands however, there are no industrial processes that use asymmetric hydrosilylation. The asymmetric hydrosilyation of olefins to alkylsilanes (and the corresponding alcohol) can be accomplished with palladium catalysts that contain chiral monophosphines with high enantioselectivities (up to 96% ee) and reasonably good turnovers (S/C = 1000) [96]. Unfortunately, high enantioselectivities are only limited to the asymmetric hydrosilylation of styrene derivatives [97]. Hydrosilylation of simple terminal olefins with palladium catalysts that contain the monophosphine, MeO-MOP (67), can be obtained with enantioselectivities in the range of 94-97% ee and regioselectivities of the branched to normal of the products of 66/43 to 94/ 6 (Scheme 26) [98.99]. 

As outlined in Section II,E, ketone and imine groups are readily hydrogenated via a hydrosilylation-hydrolysis procedure. Use of chiral catalysts with prochiral substrates, for example, R,R2C=0 or R,R2C=N— leads to asymmetric hydrosilylation (284, 285 Chapter 9 in this volume) and hence optically active alcohols [cf. Eq. (41)]. 

Hydrosilylation of unsaturated organic molecules is an attractive organic reaction. Asymmetric hydrosilylation of prochiral ketones or imines provides effective routes to optically active secondary alcohols or chiral amines (Scheme 756). These asymmetric processes can be catalyzed by titanium derivatives. The ( A ebthi difluoro titanium complex has been synthesized from the corresponding chloro compound.1659 This compound results in a very active system for the highly enantioselective hydrosilylation of acyclic and cyclic imines and asymmetric hydrosilylation reactions of ketones including aromatic ketones.1661,1666,1926-1929 An analogous l,l -binaphth-2,2 -diolato complex catalyzes the enantioselective hydrosilylation of ketones.1... 

Enantioselective reduction of simple ketone carbonyls is possible, but catalysts that deliver consistently high selectivities in such reactions have been elusive [61-64]. More success has been recorded in the asymmetric reduction of functionalized ketones and imines (reviews [65,66]). Two types of stoichiometric reductants are used dihydrogen and dihydrosilanes (reviews ref. [67,68]), but as the mechanism of hydrosilylation is highly controversial [68], we will discuss only the former. 

More recently, the asymmetric hydrosilylation of aryl ketones and aryl imines has been developed using copper catalysts. " In this case, axially chiral biaryl bisphos-phine ligands boimd to copper generate remarkably active catalysts for tihe hydrosilylation of ketones. These reactions occur with high selectivity using the hydrosilane polymer... 

Asymmetric Hydrosilylation of Unsaturated Carbon-Heteroatom Bonds. Asymmetric, catalytic hydrosilylation of prochiral ketones with substituted silanes or siloxanes gives silyl ethers that can be easily hydrolyzed to chiral alcohols. Similarly, prochiral imines undergo asymmetric hydrosilylation to give A-silylamines and, after subsequent hydrolysis, chiral amines (Scheme 32). 

The asymmetric catalytic reduction of ketones (R2C=0) and imines (R2C=NR) with certain organohydrosilanes and transition-metal catalysts is named hydrosilylation and has been recognized as a versatile method providing optically active secondary alcohols and primary or secondary amines (Scheme 1) [1]. In this decade, high enantioselectivity over 90% has been realized by several catalytic systems [2,3]. Therefore the hydrosilylation can achieve a sufficient level to be a preparative method for the asymmetric reduction of double bond substrates. In addition, the manipulative feasibility of the catalytic hydrosilylation has played a major role as a probe reaction of asymmetric catalysis, so that the potential of newly designed chiral ligands and catalysts can be continuously scrutinized. 

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