A-Siloxy ketones

Cationic Rh(I) catalysts containing (/ ,/ )-i-Pr-DuPHOS promote asymmetric intramolecular hydrosilylation of certain a-siloxy ketones with high selectivity (Scheme 8) (25). Reaction of 4-dimethylsiloxy-2-butanone produces an (/ )-l,3-[Pg.74]

In contrast, Fleming and coworkers proposed another mechanism involving a Brook rearrangement coupled with desilylative /J-elimination for similar reactions of a-siloxy ketones 131 with phenyldimethylsilyllithium to give silyl enol ethers 132 (equation 87) no trimethylsilyl enol ether 133 was detected in the reaction mixture203. 

As above (eq 1), a major drawback of this reagent is the lack of a readily available enantiomer. There are many alternative methods for the enantioselective propionate aldol reaction. The most versatile chirally modified propionate enolates or equivalents are N-propionyl-2-oxazolidinones, a-siloxy ketones, boron enolates with chiral ligands, as well as tin enolates. Especially rewarding are new chiral Lewis acids for the asymmetric Mukaiyama reaction of 0-silyl ketene acetals. Most of these reactions afford s yw-aldols good methods for the anri-isomers have only become available recently. ... 

Figure 4. Oxazaborolidine-catalyzed horane reduction of a-siloxy ketones...

In 1992, Thornton et al. reported that Mn(salen) (43) catalyzed the asymmetric oxidation of silyl enol ethers to give a mixture of a-siloxy and a-hydroxy ketones, albeit with moderate enantioselectivity (Scheme 28).135 Jacobsen et al. examined the oxidation of enol esters with Mn(salen) (27) and achieved good enantioselectivity.136 Adam et al. also reported that the oxidation of enol ethers with (27) proceeded with moderate to high enantioselectivity.137 Good substrates for these reactions are limited, however, to conjugated enol ethers and esters. Based on the analysis of the stereochemistry,137 enol ethers have been proposed to approach the oxo-Mn center along the N—Mn bond axis (trajectory c, vide supra). 

The key intermediate in the synthesis of the derivatives of 19-F3-androstane is the trifluoro analogue of the Wieland-Miescher ketone. Its preparation involves a Diels-Alder reaction between a trifluoromethyi ketone and a siloxy diene. Another original step is the regioselective reduction of a diketone only the ketone function in P of CF3 (probably activated by this substituent) is reduced (Figure 4.6). " Then, a succession of classical reactions leads to derivatives of androstane from the trifluoro analogue of the Wieland-Miescher ketone (Figure 4.7). ... 

Cyclopentanones may also be synthesized from a,/ -unsaturated ketones and diiodo-methane. The ketone is converted to the O-silyl enol, and carbene is added to the enol double bond using the Simmons-Smith reaction (see p. 74f.). Thermal rearrangement of the resulting 1-siloxy-l-vinylcydopropane and add-catalyzed hydrolysis of the silyl enol ether leads to cyclopentanones in excellent yields (C. Girard, 1974). Very high temperatures, however, are needed, and this obviously limits the generality of this rearrangement reaction. 

The formation of an a-siloxy Rh(III) intermediate resulting from initial transfer of the silyl moiety to the ketone oxygen (as opposed to a Rh(III) alkoxide) has been postulated based on spin-trapping experiments and EPR studies. Ojima,... 

The catalyzed reduction has a wide scope for various ketones with excellent enantioselectivity (Table 6). The protocol was successfully applied to the reduction of a-siloxy and tetahydropyranyloxy ketones (entry l),1074 cr-bromo and cr-chloroacetophenne (entry 2),1091-1094 trihalomethyl ketones (entry 3),1095-1099 a-sulfonyl ketones (entry 4),1100... 

JCS Perkin I 197 (stereochemistry using chiral alkoxide ligand), 979 (stereochemistry) (1982) CC 1600 (1986) (a-alkoxy or -siloxy ketone diastereoselectivity)... 

Since Hassner s initial report in 1975,7 oxidation of an enol silyl ether with peracid has been a reliable method for the preparation of a-siloxy and ot-hydroxy ketones. However, the submitters have found that, if the enol silyl ether possesses certain structural features, the reaction, with more than two equivalents of the oxidant, affords oc.a -dihydroxylated ketones (i.e., introduction of two oxygen atoms in a single-step) instead of the expected monohydroxylated compounds.8... 

Asymmetric epoxidation of silyl enol ethers mediated by a derivative of 3 (possessing a 3-nitro-phenyl group instead of a pentafluorophenyl group) gave a-hydroxy ketones with up to 62% ee. These reactions were shown to proceed through unstable a-siloxy epoxides5. 

Evolution of the method has allowed the insertion of two oxygen atoms in a single step (e.g. preparation of a-a -dihydroxy ketones). Depending on the structural features of the silyl enolate, treatment of a mixture of enolate and solid KHCO3 with cpba, followed by acidification, affords the a-a -dihydroxy ketone in good yields. When bulky tripropylsilyl groups are present (equation 5a), the hydroxy siloxy ketone 10 is the major product. The conversion of 11 to 12 shown in equation 5b is highly chemoselective. 

Transesterification can be used to cleave the acyl group from an ester to release the alcohol. The mildness of the reaction conditions enables chemoselective transformation. A siloxy group /S to a ketone group was not eliminated (Eq. 225) [524], and formation of an epoxide from the unprotected bromohydrin did not occur (Eq. 226) [525]. Similarly, in the synthesis of an avermectin derivative, delactonization was carried out by the titanium-based method as shown in Eq. (227) [526]. 

These side reactions can be minimized by adding trimethylsilyl chloride to the reaction mixture as an alkoxide scavenger. This traps the enediolate dianion as a bis-silyl enol ether, and traps the sodium or potassium alkoxides, which are catalysts for the Dieckmann ring closure, as neutral silyl ethers." The resultant bis-siloxy cycloalkenes are either isolated or converted in situ to a-hydroxy ketones by alcoholysis or by acid hydrolysis. ... 

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