Subject trimethylsilyl enol ether

More traditional carbon nucleophiles can also be used for an alkylative ring-opening strategy, as exemplified by the titanium tetrachloride promoted reaction of trimethylsilyl enol ethers (82) with ethylene oxide, a protocol which provides aldol products (84) in moderate to good yields <00TL763>. While typical lithium enolates of esters and ketones do not react directly with epoxides, aluminum ester enolates (e.g., 86) can be used quite effectively. This methodology is the subject of a recent review <00T1149>. 

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

The ester I gives alternative stereoisomers when subjected to Claisen rearrangement as the lithium enolate or as the trimethylsilyl enol ether. Analyze the respective transition states and develop a rationale for this observation. 

Accordingly, trimethylsilyl enol ethers are enolate precursors (Figure 10.16). Fortunately, they can be prepared in many ways. For instance, silyl enol ethers are produced in the silylation of ammonium enolates. Such ammonium enolates can be generated at higher temperature by partial deprotonation of ketones with triethylamine (Figure 10.18). The incompleteness of this reaction makes this deprotonation reversible. Therefore, the regioselectivity of such deprotonations is subject to thermodynamic control and assures the preferential formation of the more stable enolate. Consequently, upon... 

The addition of l,l-bis(seleno)alkyllithiums at the C-3 site of enals and enones produces enolates which can be trapped with various electrophiles (Scheme 140, b-d Schemes 149 and 150). Silylation of the litiiium enolates with trimethylsilyl chloride leads to the corresponding silyl enol ethers (Scheme 140, c), which can then be subjected to further reactions. 

Similarly, (tropone)iron complexes can also be subjected to this reaction (Scheme 4-25). Treatment of an (T -tropone)iron complex with trimethylsilyl triflate provides an Tj -dienyliumiron complex salt with an additional silyl enol ether moiety. 

The protection of the hemiacetal hydroxyl in Step B-2 was followed by a purification of the dominant stereoisomer. In Step C-l, the addition of the C(6) methyl group gave predominantly the undesired a-stereoisomer. The enolate was trapped as the trimethylsilyl ether and oxidized to the enone by Pd(OAc)2. The enone from sequence C was then subjected to a Wittig reaction. As in several of the other syntheses, the hydrogenation in Step D-2 was used to establish the configuration at C(4) and C(6). 

Having the desired alkyl bromide in hand, the O-alkylation was then explored. Various combinations of both sodium and potassium bis(trimethylsilyl)amide, as well as using 18-crown-6 ether, hexamethylpho-sphoramide, and HMPA with sodium iodide, were tried to couple 121 and 134, without success (Scheme 27). After this disappointing result, hope was reinstated after a paper by the Ley group demonstrated other conditions that were successful in O-alkylating an enolate. In this publication, the 0-mesylate was used instead of the bromide, as well as sodium hydride as the base, with 15-crown-5 ether as the cation-sequestering agent. The mesylate was synthesized from alcohol 134 with mesyl chloride and was subjected to the same conditions. Unfortunately, this was not successful, nor was the bromide under Ley s conditions. 

---