Carbon silylation

ElectrophiHc substitutions with carbon and hetero electrophiles a to the carbonyl group of aldehydes and ketones are among the most important synthetic operations. Such regio-, diastereo-, and enantioselective substitutions can be carried out efficiently with the SAMP/RAMP hydrazone methodology [3]. For cases where virtually complete asymmetric inductions could not be attained, an alternative approach based on a-silylated ketones 2 was developed [4]. They can be prepared easily from ketones 1 in high enantiomeric purity (ee > 98%) by asymmetric carbon silylation employing the SAMP/RAMP hydrazone method (Fig. 1.1.1). After the introduction of various electrophiles via classical enolate chemistry with excellent asymmetric inductions, the desired product ketones 3... 

V,7V-Diethylcarbamoyl trimethylsilane has been prepared by the reaction of bis(trimethylsilyl) sulphide with bis(A,A-diethylcarbamoyl) mercury (Scheme 30)16. Silylation of the carbamoyl cuprate reagent derived from a lithium amide, by addition of copper(I) cyanide and subsequent exposure to carbon monoxide (1 atm), is also effective75,110. Poor to moderate yields of carbamoyl silanes may be isolated by treatment of lithium silylamides with carbon monoxide and methyl iodide, in a reaction sequence involving a nitrogen to carbon silyl shift in an intramolecular silylation (Scheme 31)111. 

Another very elegant reaction is the synthesis of carbon-silylated isoxazoles213 by means of a 1,3-dipolarophilic cycloaddition of nitrile oxide with silylated acetylenes (7), (12) (Scheme 52). If mesitylnitrile oxide (361) and 3,3-dimethyl-3-sila-l, 4-pen-... 

The main product in hydrosilation of a,P-unsaturated ketones and aldehydes catalyzed by chloro-platinic acid, platinum on alumina, or metallic nickel is the corresponding silyl enol ether. With nickel catalyst, product distribution is highly dependent on the enone structure. Hydridosilanes add to a, -unsaturated esters, producing the corresponding silyl enolate as well as carbon silylated products. The course of addition depends on substrate structure and the hydridosilane utilized. Thus, triethylsilane undergoes 1,4-addition to methyl acrylate in the presence of chloroplatinic acid, while trichlorosilane with either chloroplatinic acid or Pt/C gives the -silyl ester (Scheme 65). ... 

Kyoda, M., Yokoyama, T, Kuwahara, T., Maekawa, IL, and Nishiguchi, L, Mg-promoted regioselective carbon-silylation of a-phosphorylacrylate derivatives, Chem. Lett., 228, 2002. 

Reaction at Oxygen or Carbon Silylation, Acylation and Alkylation... 

Since silicon is more electropositive than carbon, silyl-amines reasonably might be expected to be more basic than the corresponding organic amines. They are, in fact, much weaker bases. Offer an explanation. 

To overcome the limitation of the high stability of the aluminum enolates, the oxygen atom has been transformed to silyl enol ethers, enol acetates, and allyl enol carbonates. Silyl enol ethers and enol acetates are precursors to lithium enolates. Enol acetates and allyl enol carbonates are precursors of cx-allylated adducts via the Tsuji-Trost rearrangement [75-77]. The silylation of aluminum enolates using TMSOTf is well established [78], although in some cases the isolation is difficult [33]. Silyl enol ethers allow further modification to be performed as they behave as lithium enolates (Scheme 15). A recent application can be found in the silylation of the conjugate addition adduct (/ )-((3-(but-3-en-l-yl)-3-methylcyclopent-l-en-l-yl)oxy)triethylsilane which allows aldol condensation to form an intermediate in the synthesis of Clavirolide C [79], a diterpene with a trans-bicyclo[9.3.0] tetradecane structure (Scheme 16) [80]. 

Alkyl halides and sulfonates are the most frequently used alkylating acceptor synthons. The carbonyl group is used as the classical a -synthon. O-Silylated hemithioacetals (T.H. Chan, 1976) and fomic acid orthoesters are examples for less common a -synthons. In most synthetic reactions carbon atoms with a partial positive charge (= positively polarized carbon) are involved. More reactive, "free carbocations as occurring in Friedel-Crafts type alkylations and acylations are of comparably limited synthetic value, because they tend to react non-selectively. 

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

Treatment of O-silyl enols with silver oxide leads to radical coupling via silver enolates. If the carbon atom bears no substituents, two such r -synthons recombine to symmetrical 1,4-dicarbonyl compounds in good vield (Y. Ito, 1975). 

If a Michael reaction uses an unsymmetrical ketone with two CH-groups of similar acidity, the enol or enolate is first prepared in pure form (p. llff.). To avoid equilibration one has to work at low temperatures. The reaction may then become slow, and it is advisable to further activate the carbon-carbon double bond. This may be achieved by the introduction of an extra electron-withdrawing silyl substituent at C-2 of an a -synthon. Treatment of the Michael adduct with base removes the silicon, and may lead as well to an aldol addition (G. Stork, 1973, 1974 B R.K. Boeckman, Jr., 1974). 

A highly successful route to stereoisomers of substituted 3-cyclohexene-l-carboxylates runs via Ireland-Claisen rearrangements of silyl enolates of oj-vinyl lactones. The rearrangement proceeds stereospeaifically through the only possible boat-like transition state, in which the connecting carbon atoms come close enough (S. Danishefsky, 1980 see also section 4.8.3, M. Nakatsuka, 1990). 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Preparation of o,/3-Unsaturated Carbonyl Compounds by the Reactions of Silyl Enol Ethers and Enol Acetates with Ally Carbonates... 

The reaction can be applied to the synthesis of q, /3-unsaturated esters and lactones by treatment of the ketene silyl acetal 551 with an allyl carbonate in boiling MeCN[356]. The preparation of the q,, 3-unsaturated lactone 552 by this method has been used in the total synthesis of lauthisan[357]. 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

Hydride attacks regioselectively at the Si-substituted carbon in the hydro-genolysis of the silylated allylic carbonate 626 with formate, affording the allylic silane 627[I42]. 

Silylation of alcohols, amines and carboxylic acids with hydrosilanes is catalyzed by Pd catalysts[l 19], Based on this reaction, silyl protection of alcohols, amines, and carboxylic acids can be carried out with /-butyldimethylsilane using Pd on carbon as a catalyst. This method is simpler and more convenient than the silylation with /-butyldimethylsilyl chloride, which is used commonly for the protection. Protection of P-hydroxymethyl-(3-lactam (125) is an example 120]. 

The prefix sila- designates replacement of carbon by silicon in replacement nomenclature. Prefix names for radicals are formed analogously to those for the corresponding carbon-containing compounds. Thus silyl is used for SiH3—, silyene for —SiH2—, silylidyne for —SiH<, as well as trily, tetrayl, and so on for free valences(s) on ring structures. 

Silicon—Carbon Bond-Forming Reactions. After the Rochow-MbUer direct process, the hydro silylation reaction (139),... 

The silyl and stannyl substituents are crucial to these reactions in two ways. In the electrophilic addition step, they act as electron-releasing groups promoting addition and also control the regiochemistry. A silyl or starmyl substituent strongly stabilizes carboca-tion character at the /3-catbon atom and thus directs the electrophile to the a-carbon. The reaction is then completed by the limination step, in which the carbon-sihcon or carbon-tin bond is broken. 

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