Ketones, reduction with silanes

Scheme 3.2S Solvent dependency of diastereoselective glycid ketone reduction with trimethoxy silane.

The quininium and quinidinium fluoride catalysts, 10 (R=H etc., X=F) and 8 (R=H, X=F), were used for the asymmetric reduction of alkyl aryl ketones in conjunction with silanes.1751 One of the most efficient silanes proved to be tris(trimethylsiloxy)silane, which together with 8 (R=H, X=F) reduced acetophenone to give the alcohol 102 in almost quantitative yield with 78 % ee, as shown in Scheme 31. The... 

The asymmetric organocatalytic transformation of a ketone into an alcohol may be realized with the combination achiral silanexhiral phase-transfer catalyst, such a quaternary ammonium salt. The final alcohol is then recovered by an additional hydrolytic step. The asymmetric reduction of aryl alkyl ketones with silanes has been reported (ee-values up to 70%), the catalysts utilized being ammonium fluorides prepared from the quinine/quinidine series (e.g., 18 in Scheme 11.6) [19]. (For experimental details see Chapter 14.21.1). The more appropriated silanes were (Me3SiO)3SiH or (MeO)3SiH (some examples are... 

General Procedure for the Reduction of Aromatic Ketones with Silanes Under Phase-Transfer Conditions [94] (p. 398)... 

Ketones in alcohol solutions give mixed ethers with triethylsilane and trifluoroacetic acid, presumably via the hemiketal (or ketal). Similar results were obtained with ketones and silylated alcohols. Studies of the acid-catalyzed reduction of alcohols with silanes provide strong support for the postulate that carbonium ions are intermediates. ... 

Silanes normally reduce aldehydes or ketones under catalytic conditions to the silyl ethers. However, with certain catalysts such as nickel sulfide,Co2(CO)8, or (Ph3P)3RhCl, carbonyl compounds react with silanes to yield an equilibrium mixture of enol silyl ethers (Scheme 17). In a similar vein, the silyl-hydroformylation reaction of cycloalkenes with CO and silanes may be a practical way to prepare enol silyl ethers. An example is the preparation of compound (49). Catalytic 1,4-hydrosilation of a, -un-saturated ketones or aldehydes gives the corresponding enol silyl ethers. The reaction is similar to the reductive silylation referred to previously, but the reaction conditions are neutral and milder. The formation of the enol silyl ether (50) is outlined below. ... 

Polymethylhydrosiloxane (PMHS), a safe and inexpensive polymer co-product of the silicon industry, is an efficient alternative reducing agent for C=0 and C=N bonds when associated with catalysts (1). Mimoun et al. recently reported a new system based on zinc hydride catalysts which enables the chemoselective reduction of unfunctionalized and a,/ -unsaturated- aldehydes, ketones and esters (2). Because gummy silicon residues, which are usually associated with silane reductions, do not form, this PMHS system is attractive for synthetic / industrial purposes. Nevertheless, in contrast to tin-catalyzed reductions of ketones with PMHS... 

The rhodium(I)-catalyzed reduction of ketones with silanes is also subject to enantioselection by chiral ligands, which can be a bipyridine derivative, cyclic phosphonites and phosphites, " or diferrocenyl dichalcogenides. ... 

In 1992 the Bullock and Norton groups reported the reduction of aldehydes and ketones under similar conditions, and isolated an isopropyl alcohol complex formed thereby (eq 44) [75] similar results have recently been reported with H2Re(NO)(CO)(PR3)2/CFjC02H by Bakhmutov and co-workers [76]. These reactions resemble the ionic hydrogenations long known with silanes as hydride donors [77],... 

Catalytic Hydrosilylation of Unsaturated Carbon-Heteroatom Bonds. Hydrosilylation of ketone produces silyl ether, which can be easily converted to alcohol via an additional hydrolysis (deprotection) step (Scheme 28). Analogously, hydrosilylation of imine leads to the formation of silylamine, which can be conveniently transformed to amine. Hydrosilylation of carbonyl (imine) group with subsequent hydrolysis is often referred to as the reduction by silanes. 

Later, Sun s group also used their pipecolinic acid derivative 87 for the first efficient reduction of aliphatic and aromatic ketones with silane 2 in moderate to high enantioselectivity [184]. A plausible transition state was proposed in order to explain the results observed, where the catalyst 87 would act as a tridentate activator and would promote the hydrosUylation of ketones through the heptacoordinate silicon structure depicted in Fig. 12. 

Dimethyl(phenyl)silane reduces aldehyde and ketone carbonyls with the aid of fluoride ion or acid. a-Acylpropionamides, 1-aminoethyl ketones, and 1-alkoxyethyl ketones are readily converted into the corresponding -hydroxy amides, o -amino alcohols, and a-alkoxy alcohols, respectively. The stereoselectivity is complementary and generally high erythro (or syn) isomers are obtained with trifluoroacetic acid (TFA), whereas threo (or anti) isomers are obtained with fluoride ion activator (eq 1). The erythro selectivity in the acid-promoted carbonyl reduction is ascribed to a proton-bridged Cram s cyclic transition state. On the other hand, the threo selectivity in the fluoride-mediated reduction is explained in terms of the Felkin-Anh t) e model, wherein a penta-or hexacoordinated fluorosilicate is involved. No epimerization at the chiral center is observed during the reaction. 

Hypercoordinate silicates formed by reaction of PMHS with KF, TBAF, or other nucleophiles, can reduce ketones, aldehydes, and esters (eq 12). With proper nucleophile choice, aldehydes can be reduced selectively over ketones, and ketones over esters (eq 13). Halides, nitriles, nitro groups, and olefins survive these conditions, but enones often undergo both 1,2- and 1,4-reductions. PMHS is worse than other silanes for performing enantioselective reductions with chiral fluoride sources, affording alcohols in only 9-36% ee. ... 

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