Silyl Lewis Acids

An increase in the strength of silyl Lewis acid leads to an increase in the rate of the ABENA process and allows one to use milder conditions. In addition, the rate ratio K4/K2 (Chart 3.20) sharply increases. For example, the generation rate of respective BENA is approximately equal to the rate of consumption of the corresponding intermediate SENA in double silylation of 2-nitropropane with Me3SiCl (187). This SENA was not detected among the products of silylation of 2-nitropropane in the presence of even a smaller amount of Me3SiOTf. 

The nature of products (373) depends on a number of factors (486, 487). As can be seen from the lower part of the scheme, the reactions of compounds, in which R3 is H or alkyl, using weak silyl Lewis acids (X is a poor leaving group)... 

The process under consideration could be discussed in terms of ring-chain tautomerism of nitronates (378=381) (see the lower part of Scheme 3.215), the more so that such examples were documented for proton analogs of similar SENA (492). However, both nitronates ((378) and (381)), which were prepared by independent syntheses, are quite stable, and therefore their isomerization in the presence of a silyl Lewis acid should involve ring-chain tautomerism of cations. Evidently, cyclization of nitronate (378) is attributed to high electrophilicity of the carbon atom of the carbonyl group, provided that this group is not involved in the conjugation chain. 

It is very likely, that this reaction occurs due to the equilibrium between trimethylsilyl halide and a nitrogen-containing nucleophile, which increases the electrophilicity of silyl Lewis acids. It should be noted that the configuration of stereocenters at the carbon atoms of the oxazine ring is partially distorted. Hence, it is assumed that the reaction proceeds through the intermediate cation B, which is partially isomerized into the stereoisomeric cation B through the open chain cation B". 

The probable pathway resulting in the stereoselective formation of silylated ene nitrile (586) from enoxime (584) is presented on the right of Scheme 3.282. At higher temperature, the latter eliminates trimethylsilanol to give ene-nitrile (586) under the action of silyl Lewis acid (TfOSiMe3). Evidently, the reaction of compound (585) with TfOSiMe3 at room temperature involves initial silylation of the nitrogen atom to form the cationic intermediate B, which is deprotonated with triethylamine, followed by the thermodynamically favorable l,3-N,C-shift... 

Overall, it is possible to divide the silyl Lewis acids into two groups, depending on how strong the counter anion interacts with the silicon atom as shown in Scheme 2. In the case where a very weakly coordinating anion is part of the compound, one could consider that a free silyl cation is present. However, the silyl cation is very strong and will be coordinated by solvent molecules like acetonitrile or toluene [25, 26]. This complex could activate, for example, a carbonyl group. Whether the carbonyl group replaces the solvent molecule is not known. In the case... 

The role of the ligand has been found to be crucial in the silyl Lewis acid Mukaiyama aldol reaction, which opens interesting applications for synthetic organic chemistry. When TMSOTf induces the reaction, the silyl group of TMSOTf remains in the product and that of the silyl enol ether becomes the catalyst for the next catalytic cycle however, if the reaction is promoted by TMSNTf2, the silyl group of the catalyst is not released from... 

Scheme 4 The anion-stabilized silylium ion 17 and conventional silyl Lewis acids 18-20...

Lewis Acid Mediated Alkylation of Silyl Enolethers- SNi like alkylations... 

Lewis acid promoted condensation of silyl ketene acetals (ester enolate equiv.) with aldehydes proceeds via "open" transition state to give anti aldols starting from either E- or Z- enolates. 

Mukaiyarna-Johnson AJdoJ- Lewis acid promoted condensation of silyl enol ethers with acetals ... 

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]... 

Titanium(IV) is a powerful but selective Lewis acid which can promote the coupling of allylsilanes with carbonyl compounds and derivatives In the presence of titanium tetrachlonde, benzalacetone reacts with allyltnmethylsilane by 1,4-addition to give 4-PHENYL-6-HEPTEN-2-ONE. Similarly, the enol silyl ether of cyclopentanone is coupled with f-pentyl chloride using titanium tetrachlonde to give 2-(tert-PENTYL)CYCLOPENTANONE, an example of a-tert-alkylation of ketones. 

The Lewis acid-catalyzed addition of silyl kelene acetals occurred m high yield, and when the ketene acetal bore a substituent, the reactions occurred with modest diastereofacial selectivity [d] (equation 7) (Table 3)... 

Me3Si)2NH, Me3SiCl, Pyr, 20°, 5 min, 100% yield. ROH is a carbohydrate. Hexamethyldisilazane (HMDS) is one of the most common silylat-ing agents and readily silylates alcohols, acids, amines, thiols, phenols, hydroxamic acids, amides, thioamides, sulfonamides, phosphoric amides, phosphites, hydrazines, and enolizable ketones. It works best in the presence of a catalyst such as X-NH-Y, where at least one of the groups X or Y is electron withdrawing." Yttrium-based Lewis acids also serve as catalysts. ... 

Lewis acids are iilso effecdve to induce the nucleophihc subsdmdon of dlyhc nitro compotmds. These compotmds react v/ith dlyltrimethylsiiane," silyl enolates," or cy-anotrimethylsilane" in the presence of SnCLi to give subsdmdon products, respecdvely fsee Eqs. 7.24-7.26. ... 

The use of boron trifluoride-diethyl ether complex as the Lewis acid in these reactions promotes silyl group migration and gives rise to the formation of tetrahydrofurans with excellent stereoselectivity82. 

The Lewis acid mediated addition of silyl enol ethers or silylketcne acetals to oc-alkoxyaldehydcs is the most versatile and reliable method of providing chelation control in aldol-type additions3. The stereochemical outcome is as predicted by Cram s cyclic model11 ... 

The chiral (V-camphanoyl iminium ion 7, prepared by hydride abstraction from 2-camphanoyl-l,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline 6 (see Appendix) with triphenylcarbenium te-trafluoroborate, reacts with silyl enol ethers to give 1-substituted tetrahydroisoquinoline derivatives with reasonable diastereoselectivity, 0°. On addition of titanium(IV) chloride, prior to the addition of the silyl enol ether, the diastereoselectivity gradually rises to an optimum at 2.5 equivalents of the Lewis acid, but the yield drops by 20%. 

The Lewis acid induced reaction of silyl enol ethers and silyl ketene (thio)acetals with 4-acetoxyazetidinones is often used for introduction of a carbon substituent in the 4-position of the jS-lactam ring. Numerous examples are known, both with and without substituents at nitrogen, some of which are shown. 

As an alternative to lithium enolates. silyl enolates or ketene acetals may be used in a complementary route to pentanedioates. The reaction requires Lewis acid catalysis, for example aluminum trifluoromethanesulfonate (modest diastereoselectivity with unsaturated esters)72 74 antimony(V) chloride/tin(II) trifluoromethanesulfonate (predominant formation of anti-adducts with the more reactive a,/5-unsaturated thioesters)75 montmorillonite clay (modest to good yields but poor diastereoselectivity with unsaturated esters)76 or high pressure77. 

A high degree of syn selectivity can be obtained from the addition of enamines to nitroalkenes. In this case, the syn selectivity is largely independent of the geometry of the acceptor, as well as the donor, double bond. Next in terms of selectivity, are the addition of enolates. However, whether one obtains syn or anti selectivity is dependent on both the geometry of the acceptor and the enolate double bond, whereas anti selectivity of a modest and unreliable level is obtained by reaction of enol silyl ethers with nitroalkenes under Lewis acid catalysis. 

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