Trimethylsilyl enantioselective protonation

Monoalkyl ethers of (R,R) 1,2-bis[3,5-bis(trifluoromethyl)phenyl]ethanediol, 24, have been examined for the enantioselective protonation of silyl enol ethers and ketene disilyl acetals in the presence of SnCU (Scheme 12.21) [25]. The corresponding ketones and carboxylic acids have been isolated in quantitative yield. High enantioselectivities have been observed for the protonation of trimethylsilyl enol ethers derived from aromatic ketones and ketene bis(trimethylsilyl)acetals derived from 2-arylalkanoic acids. 

Silyl enol ethers, known as chemically stable and easy handled enolates, can be protonated by a strong Bronsted acid. Our group demonstrated that a Lewis acid-assisted Bronsted acid (LBA 17), generated from optically pure binaphthol and tin tetrachloride, was a chiral proton source of choice for asymmetric protonation of silyl enol ethers possessing an aromatic group at the a-position [33, 34]. Binaphthol itself is not a strong Bronsted acid, however, LBA 17 can proto-nate less reactive silyl enol ethers since the acidity of the phenolic protons of 17 is enhanced by complexation with tin tetrachloride. The catalytic asymmetric protonation of silyl enol ethers was accomplished for the first time by LBA 18. Treatment of ketene bis(trimethylsilyl)acetal 60 with 0.08 equiv of LBA 18 and a stoichiometric amount of 2,6-dimethylphenol as an achiral proton source afforded (S)-2-phenylpropanoic acid (61) with 94% ee (Scheme 10) [35]. LBA 19 derived from binaphthol monoisopropyl ether has been successfully applied to the enantioselective protonation of meso 1,2-enediol bis(trimethylsilyl) ethers under stoichiometric conditions [36]. 

Catalytic enantioselective protonation of prochiral ketone enolates is a beneficial route to optically active carbonyl compounds possessing a tertiary asymmetric carbon at the a-position. In the asymmetric protonation of trimethylsilyl enolates with methanol, BINAP-AgF has been found to act as a chiral catalyst [90,91], which is also known to catalyze asymmetric allylation of aldehydes with allylic trimethoxysilanes [42] as well as asymmetric aldol reaction with trimethoxysilyl enolates [54]. This protonation can be most effectively performed using 6 mol% ofBINAP and 10 mol% of... 

Table 18.3 Enantioselective protonation of trimethylsilyl enolates (71) with methanol catalyzed by (R)-BINAP- AgF complex.

In the presence of 8 mol % SnCU, 10 mol % (/ )-BINOL-Me, and stoichiometric amounts of 2,6-dimethylphenol as an achiral proton source, the protonation of the ketene bis(trimethylsilyl)acetal derived from 2-phenylpropanoic acid proceeded at -80 °C to give the S carboxylic acid with 94 % ee. ( )-BINOL-Me is far superior to (l )-BlNOL as a chiral proton source during the catalytic protonation, and 2,6-dimethylphenol is the most effective achiral proton source. In addition, for high enantioselectivity it is very important that the molar quantity of SnCU should be less than that of (i )-BINOL-Me. For reaction of 2-phenylcyclohexanone, however, the use of tin tetrachloride in molar quantities lower than BINOL-Me substantially reduced the reactivity of the chiral LBA. Excess SnCU per chiral proton source, in contrast, promoted this protonation. In the protonation of silyl enol ethers less reactive than ketene bis(trialkylsilyl) acetals, chelation between excess tin tetrachloride and 2,6-dimethylphenol prevents the deactivation of the chiral LBA (Sch. 4). This catalytic... 

Nakai and a coworker achieved a conceptually different protonation of silyl enol ethers using a chiral cationic palladium complex 40 developed by Shibasaki and his colleagues [61] as a chiral catalyst and water as an achiral proton source [62]. This reaction was hypothesized to progress via a chiral palladium enolate which was diastereoselectively protonated by water to provide the optically active ketone and the chiral Pd catalyst regenerated. A small amount of diisopropylamine was indispensable to accomplish a high level of asymmetric induction and the best enantioselectivity (79% ee) was observed for trimethylsilyl enol ether of 2-methyl-l-tetralone 52 (Scheme 11). 

In the same context, the asymmetric protonation of 2-methyl-1-tetralone-derived trimethylsilyl enol ether was achieved by Levacher et al. in the presence of a cinchona alkaloid [DHQ]2AQN derived from hydroquinine as the organo-catalyst and citric acid as the proton source in DMF. This reaction occurred with a good yield and an enantioselectivity of 73% ee, as shown in Scheme 10.12. 

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