Silyl enol ethers tertiary halides

A related tert-butylation procedure in which the silyl enol ether is added to a mixture of titanium tetrachloride and tert-butyl chloride gives rise to distinctly lower yields. This is also the case if the tertiary halide is added to a mixture of silyl enol ether and titanium tetrachloride. ... 

Silyl enol ethers and silyl ketene acetals also offer both enhanced reactivity and a favorable termination step. Electrophilic attack is followed by desilylation to give an a-substituted carbonyl compound. The carbocations can be generated from tertiary chlorides and a Lewis acid, such as TiCl4. This reaction provides a method for introducing tertiary alkyl groups a to a carbonyl, a transformation that cannot be achieved by base-catalyzed alkylation because of the strong tendency for tertiary halides to undergo elimination. 

The best alkylating agents for silyl enol ethers are tertiary alkyl halides they form stable carbocations in the presence of Lewis acids such as TiCLj or SnCLj. Most fortunately, this is just the type of compounds that is unsuitable for reaction with lithium enolates or enamines, as elimination results rather than alkylation a nice piece of complementary selectivity. 

Silyl enol ethers of aldehydes or ketones can be used with 1 -reactive (tertiary, allylic or benzylic) alkyl halides... 

Silyl enol ethers 64 need Lewis acid catalysis which generates at least a partial positive charge on the alkyl group so they react best with tertiary, allylic, and benzylic halides, and reasonably... 

Alkylation with tertiary halides is the special preserve of silyl enol ethers. Both the familiar isomers 22 and 25 give regiospecific alkylation in good yield with Lewis acid catalysis.23 The formation of 78 is remarkable as it puts two quaternary centres next to one another. 

In addition to their use for the preparation of specific Uthium enolates, silyl enol ethers are also excellent substrates for actrf-catalysed alkylation. In the presence of a Lewis acid (e.g. TICU, SnCU, BF3 OEt2> they react readily with tertiary alkyl halides to give the alkylated product in high yield. This procedure thus complements the more-common base-catalysed alkylation of enolates which fails with tertiary haUdes. It is supposed that the Lewis acid promotes ionization of the electrophile, RX, to form the cation R+, which is trapped by the silyl enol ether to give the addition product with cleavage of the silicon-oxygen bond. 

While the greater nucleophilicity of azaenolates means that they will react with a wider range of electrophiles, their basicity, like that of lithium enolates, means that they will not react with SNl-reactive electrophiles like tertiary alkyl halides. The solution to this problem is to use silyl enol ethers, which are less reactive and so require a more potent electrophile to initiate reaction. Carbocations will do, and they can be generated in situ by abstraction of a halide or other leaving group from a saturated carbon atom. 

Allyl silanes are rather like silyl enol ethers they react with electrophiles, provided they are activated, for example by a Lewis acid. Titanium tetrachloride is widely used but other successful Lewis acids include boron trifluoride, aluminium chloride, and trimethylsilyl triflate. Electrophiles include acylium ions produced from acid chlorides, carbocations from tertiary halides or secondary benzylic halides, activated enones, and epoxides all in the presence of Lewis acid. In each case the new bond is highlighted in black. 

Reactions of Enolates and Enolate Equivalents.— Highly crowded ketones are prepared by the Lewis acid-catalysed t-alkylation of trimethylsilyl enol ethers. Stereoselection is observed in alkylations with tertiary halides which are known to solvolyse stereoselectively owing to anchimeric assistance or other factors. The alkylation can be carried out in an intramolecular fashion, but compounds having silyl enol ether and tertiary halide functions are difficult to prepare. However, Lewis acid-mediated cyclization of trisubstituted olefinic active methylene compounds provides an alternative method for the intramolecular... 

Further refinements to the alkylation of silyl enol ethers have appeared. Ketones can be alkylated at the a-position by treatment of their silyl enol ethers with tertiary alkyl halides in the presence of Lewis acids such as titanium tetrachloride or tin tetrachloride.a-Cumylation of ketones is possible using catalytic quantities of mild Lewis acids such as zinc chloride. The method can be used to couple two tertiary centres. 

FIGURE 17.48 Reaction of a silyl enol ether with a tertiary halide. 

The titanium(IV) chloride-promoted reactions of enol silyl ethers with aldehydes, ketones, and acetals, known as Mukaiyama reaction, are useful as aldol type reactions which proceed under acidic conditions (eq (23)) [20], Enol silyl ethers also undergo the Michael type reactions with enones or p.y-unsaturated acetals (eq (24)) [21]. Under similar reaction conditions, enol silyl ethers are alkylated with reactive alkyl halides such as tertiary halides or chloromethyl sulfides (eq (25)) [22], and acylated with acid halides to give 1,3-diketones (eq (26)) [23]. 

---