Lewis acids silane reductions

Reduction of ketones to triphenylsilyl ethers is effected by the unique Lewis acid perfluorotriphenylborane. Mechanistic and kinetic studies have provided considerable insight into the mechanism of this reaction.186 The salient conclusion is that the hydride is delivered from a borohydride ion, not directly from the silane. Although the borane forms a Lewis acid-base complex with the ketone, its key function is in delivery of the hydride. 

Attempts to reductive removal of the hydroxyl group from the ketol by the use of silanes and Lewis acids (see Ref. 73) gave unaltered material. Also unsatisfactory were various attempts to dehydroxylate the ketol by radical procedures. 

The reaction of conjugated enones and dienones with trimethyl- and triethyl-silane in the presence of TiCU, followed by aqueous work-up produces the corresponding saturated ketones. This Lewis acid catalysis is particularly useful for conjugated reduction of sterically hindered systems (Scheme 46). " a,p-Unsaturated esters are not reduced under these conditions. 

Silanes are widely recognized as efficient reagents for reduction of carbonyl and heterocarbonyl functionality. In the case of alkyl and arylsilanes, the reaction requires catalysis by Lewis acids or transition metal complexes 1, 3] however, with more Lewis acidic trichloro or trialkoxysilanes, an altemative metal free activation can be accomplished. Thus, it has been demonstrated that extracoordinate silicon hydrides, formed by the coordination of silanes to Lewis bases, such as tertiary amines 7a], DMF [7b] or MeCN, and so on [7], can serve as mild reagents for the reduction of imines to amines [8]. In the case of trichlorosilane, an inexpensive and relatively easy to handle reducing reagent, and DMF as a Lewis basic promoter, the intermediacy of hexacoordinate species has been confirmed by Si NMR spectro scopy [7b]. 

Chiral silyl ketene acetals (Il)-(20) were recently introduced for diastereoselective aldol-type additions. Camphor derivatives (11)-(16) are conformationally rigid with one diastereotopic face of the enol silane sterically shielded. - A -Methylephedrine derivatives (17)-(20) are likely to bind to TiCU through the NMe2 group with consequent dramatic conformational constraint.As a result the Lewis acid mediated additions to C=X occur in a highly stereoselective way. The chiral auxiliaries can then be removed (and recycled) by reduction, saponification or displacement with various nucleophiles to give useful synthetic intermediates. 

Spiroketal Reduction with Silane-Lewis Acid... 

One routine method for the functionalization of quinolines is the addition of substituents to the 2-position. Further advances in the catalytic, enantioselcctive Reissert-type reaction were reported. Quinoline 63 was treated with 2-furoyl chloride and TMSCN in the presence of Lewis acid-Lewis base bifunctional catalyst 64 followed by reduction of the corresponding enamine to afford quinoline 65 in 93% ee. Quinoline 65 was subsequently converted to (-)-L-689,560, a potent NMDA receptor antagonist <01JA6801>. Additions of ally.silanes to quinolines acylated with chloroformate esters and catalyzed by various triflate salts were reported <01T109>. 

In this context, lipshutz et al. reported in 2000 a catalytic reductive aldol reaction of enones and aldehydes with [PhsPCuHjs (5 mol%) and PhMe2SiH (150mol%) [46]. The two-step reaction was carried out in one pot, without isolation of the intermediate sUyl enol ethers, efficiently providing the b-hydroxyketones in high yield. Lewis acids such as BF3 or TiCLj are used to promote the second step involving aldol reaction of the enol silane. In place of hydrosilanes, dialkylboranes could be employed as hydride sources, circumventing the need to introduce additional Lewis acids. Here, the aldol products are formed via intermediacy of the boron-enolates, with 5y -selectively for acychc enones and antz-selectively for cycHc enones [47-50]. 

The reduction of the acetal is catalysed by a Lewis acid and goes via an oxonium ion, which coiiects hydride from the mild reducing agent triethylsilane. Silanes react only with cationic electrophiles. The oxonium ion could open either way, but this one is less hindered and possibly allows the titanium some favourable interaction with the mesylate... 

Silicon being more electropositive than hydrogen (Pauling electronegativities Si 1.90, H 2.20), silanes with Si-H bonds can reduce a variety of functional groups such as carbonyl compounds, imines, and even alcohols by transferring a hydride anion. Triethylsilane is a common reagent, and typical reaction conditions also include either a Brpnsted or a Lewis acid, as shown below for the reduction of a ketone ... 

One important development however, was the identification of a reductive trapping pathway, allowing the isolation of saturated cyclopentanones. Lewis acid promoted Nazarov cyclization of substrate 104, followed by reductive quenching by triethyl silane resulted in the formation of ketones 106 and enol silanes 107. Such a reaction process requires only 10 mol % of the Lewis acid promoter, with hydride addition occurring at the less-substituted position of the oxyallyl cation 105. Mixtures of compounds isomeric at the a-positions were isolated in these reactions due to the rapid epimerization of these centers during acidic workup. 

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