Hydrosilylation of ketones

Alternative bis-oxazolines, as well as phosphino-oxazolines (see Section 10.2) ° have also been used, although these ligands were generally less selective. However, Uemura and coworkers reported interesting results with the oxazolinylferrocene-phosphine ligand (3.153). Whilst the rhodium-catalysed 

Alkyl/alkyl ketones are challenging substrates for rhodium-catalysed asymmetric hydrosilylation and are generally reduced with low enantioselectivities using oxazoline-based hgands. However a number of alternative ligand systems have been used successfidly in the rhodium-catalysed hydrosilylation of alkyl/alkyl ketones. For example, the 8-keto ester (3.158) undergoes enantioselective 

The hydrosilylation of a symmetrical ketone with a prochiral silane leads to the possibility of asymmetric induction in the newly formed silicon stereocentre. In their best example, Takaya and coworkers reported essentially complete control of asymmetric induction using the CyBINAP hgand (3.169) and a rhodium catalyst. Pentan-3-one (3.170) and prochiral silane (3.171) are converted into the alkoxysilane (3.172), where the asymmetry is associated with the silicon atom. 

As well as rhodium-catalysed hydrosilylation, asymmetric ruthenium and titanium-catalysed hydrosilylation have also been reported. Amongst these, Buchwald s report of the hydrosilylation of ketones using titanocene catalysts and inexpensive polymethyUiydrosiloxane (PMHS) appear to be the most general. 

Reactions proceed via formation of the active titanium hydride catalyst (3.173) formed either by treatment of the precatalyst (3.174) with two equivalents of butyllithium, followed by addition of polymethylhydrosiloxane, or by reaction 

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Reaction (31) shows an example of hydrosilylation of ketones, i.e., reduction of 4-ferf-butyl-cyclohexanone affordir mainly the tmns isomer, indicating that the axial H-abstraction is favored7... 

Scheme 20 Hydrosilylation of ketones catalyzed by Fe(OAc)2 with the iV-coordinated ligand...

An iron complex-catalyzed asymmetric hydrosilylation of ketones was achieved by using chiral phosphoms ligands [68]. Among various ligands, the best enantios-electivities (up to 99% ee) were obtained using a combination of Fe(OAc)2/(5,5)-Me-Duphos in THF. This hydrosilylation works smoothly in other solvents (diethylether, n-hexane, dichloromethane, and toluene), but other iron sources are not effective. Surprisingly, this Fe catalyst (45% ee) was more efficient in the asymmetric hydrosilylation of cyclohexylmethylketone, a substrate that proved to be problematic in hydrosilylations using Ru [69] or Ti [70] catalysts (43 and 23% ee, respectively). 

In 2008, Gade and coworkers reported that the asymmetric hydrosilylation of ketones was catalyzed by the Fe complex with a highly modular class of pincer-type ligand (Scheme 22) [71]. This Fe catalyst system showed both moderate to good... 

Scheme 24 The comparison of a bis(imino)pyridine iron complex and a pyridine bis(oxazoline) iron complex for hydrosilylation of ketones...

Rh-catalysed hydrosilylations of ketones with thioether-phosphinite... 

Other metals such as iridium have also been combined to chiral sulfur-containing ligands in order to induce the chirality in the hydrosilylation of ketones. Therefore, Lemaire et al. have described the use of several chiral thiourea ligands for the iridium-catalysed hydrosilylation of acetophenone. The best but moderate enantioselectivity (52% ee) was observed with the use of a C2-symmetric monothiourea ligand (Scheme 10.49) while the employment of... 

In 2005, Riant et al. reported the synthesis of a new air-stable S/N-chelating zinc catalyst, depicted in Scheme 10.50, which was fully characterised by all spectroscopic methods. This complex, prepared from the corresponding ferrocene oxazoline, was applied to the enantioselective hydrosilylation of ketones in the presence of polymethylhydrosiloxane, PMHS, providing modest enan-tioselectivities (<55% ee). ... 

In addition. Taller and Chase have reported the use of chiral tridentate S/N/P ligands for the rhodium-catalysed hydrosilylation of ketones.The best ligand, which provided an enantioselectivity of up to 64% ee, was that bearing the shortest reach to the metal to give a tridentate ligand, as shown in Scheme 10.51. 

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. 

Scheme 6.79 Hydrosilylation of ketones [164], Dotz benzannulation chemistry [165], cobalt-mediated synthesis of angular [4]phenylenes [166], and nickel-mediated coupling polymerizations [167],...

Supported cationic rhodium(I) phosphine complexes, chiral at a men-thyl moiety, effected hydrogenation of ketones, but the 2-butanol produced from methylethylketone was optically inactive (348). Polystyrene-or silica gel-supported DIOP systems, however, are particularly effective for production of optically active alcohols (up to 60% ee) via asymmetric hydrosilylation of ketones (10, 284, 296, 366, 368 see also Section III, A,4). 

Displacement of the bound ketone by H2 was directly observed by NMR (Eq. (37)), and an approximate equilibrium constant was determined. The cationic tungsten complex can also be used for catalytic hydrosilylation of ketones. In the case of catalytic hydrosilylation of abphatic substrates using HSiEt3, the catalyst precipitates at the end of the reaction, facilitating recycle and reuse [66],... 

L. V. Dinh, J. Gladysz, Transition Metal Catalysis in Fluorous Media Extension of a New Immobilization Principle to Biphasic and Monophasic Rhodium-Catalyzed Hydrosilylations of Ketones and Enones , Tetrahedron Lett. 1999, 40,8995. 

In total, over the past six years, the chelating P,N-ligands have shown considerable promise in a variety of enantioselective processes, including transfer-hydrogenation and hydrosilylation of ketones, hydroboration of alkenes, conjugate addition to enones and Lewis-acid catalysed Diels-Alder reactions, in addition to those described above.128,341 It is anticipated that this list will continue to grow, and... 

Keying on the discovery by Zhang and co-workers (40) that mixed P-N ligands were useful in ruthenium catalyzed hydrosilylation of ketones, Frost and... 

By far, the most W-Si bonds reported in the period that this review covers involve W(CO)n or (t]S-CsRs)W-containing compounds. A significant development has been that of a recyclable catalyst for the hydrosilylation of ketones the system begins with a polar liquid substrate (ketone or ester) and finishes with a non-polar liquid product (alkoxysilane). The rest state of the catalyst is a mixture of the [BlCgFsTH salts of 36 and 37 the tungsten complex is far more active than its molybdenum analog. 

Asymmetric hydrosilylation of ketones has developed enormously since these early reports and probably there are few catalytic reactions for which the variety in ligand structure is so immense as for this reaction. Numerous reports have been published and in general oxazoline-based ligand systems seem to give the highest enantioselectivities. In the following we will mention a few... 

For many years nitrogen-based ligands were the ligands of choice for the asymmetric hydrosilylation of ketones and especially pyridincoxazolincs were highly effective [25], In Figure 18.14 a few typical examples have been collected. 

A number of P-N ligands has been reported as efficient ligands for the asymmetric hydrosilylation of ketones. We mention the phosphinooxazolines developed by Helmchen, Pfaltz, and Davis, we have seen before and mixed ligands containing planar-chiral heterocycles such as ferrocene [31] (Figure 18.17). For several ketone and silane combinations e.e. s in the high nineties were obtained. 

It has been reported that (TMS)3SiCl can be used for the protection of primary and secondary alcohols [55]. Tris(trimethylsilyl)silyl ethers are stable to the usual conditions employed in organic synthesis for the deprotection of other silyl groups and can be deprotected using photolysis at 254 nm, in yields ranging from 62 to 95%. Combining this fact with the hydrosilylation of ketones and aldehydes, a radical pathway can be drawn, which is formally equivalent to the ionic reduction of carbonyl moieties to the corresponding alcohols. 

New N-heterocyclic carbene rhodium and iridium complexes derived from 2,2 -diaminobiphenyl were successfully synthesized and their structures unambiguously characterized by X-ray diffraction (XRD) analysis. These are cata-lytically active for the hydrosilylation of ketones with diphenylsilane, although an NHC—rhodium complex was found to be the best among those investigated [45]. 

Other silicon derivatives containing Si—X—C bonds (where X is O and/or N) can be successfully prepared by using iridium-catalyzed reachons such as the asymmetric hydrosilylation of ketones and amines, the silylcarbonylation of alkenes, and the alcoholysis of Si—H bonds. Indeed, oxygenation of the latter bond to silanol also proceeds smoothly in the presence of iridium compounds. 

In 1989, the first bis(oxazoline) ligands were introduced by Nishiyama and coworkers.These bis(oxazolinylpyridines), also called py-box ligands 1 were originally used for the enantioselective hydrosilylation of ketones (Fig. 9.1). 

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