Silyl enol ethers Lewis acid promoted

The pinwheel shape of a f-butyl propionate derived silylketene acetal (see Section 2.4.2.1) was revealed by a single-crystal X-ray diffraction analysis. Several different catalysts were reported to promote the aldol-type condensation of alkyl enol ethersand silyl enol ethers with aldehydes, acetals and various other electrophiles. In some cases the reaction proceeded with high simple stereoselection. The mechanism of the Lewis acid mediated additions to acetals (see Section 2.4.2.3) was investigated in detail, as well as the uncatalyzed aldol reaction of silyl enol ethers with aldehydes promoted by the hydrophobic effect (see Section 2.4.2.1). 

Highly functionalized tetrahydropyran-4-ones can be obtained through a silyl enol ether Prins cyclization promoted by a condensation reaction of hydroxy silyl enol ethers with Lewis-acid-activated aldehydes, with high diastereoselectivity (14JOC8733). Spirooxindole tetrahydropyran-4-ones are obtained from oxa-DA reaction of acyclic a,P-unsaturated methylke-tones and isatins mediated by a bifunctional enamine-metal Lewis acid catalyst, in good yields and moderate stereoselectivities (14S1339). 

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

Lewis acid catalysis has been used to promote stepwise [2 + 2] cycloaddition of silyl enol ethers and unsaturated esters.178 The best catalyst is (C2H5)2A1C1 and polyfluoroalkyl esters give the highest stereoselectivity. The reactions give the more stable trans products. 

The use of oxygen-containing dienophiles such as enol ethers, silyl enol ethers, or ketene acetals has received considerable attention. Yoshikoshi and coworkers have developed the simple addition of silyl enol ethers to nitroalkenes. Many Lewis acids are effective in promoting the reaction, and the products are converted into 1,4-dicarbonyl compounds after hydrolysis of the adducts (see Section 4.1.3 Michael addition).156 The trimethylsilyl enol ether of cyclohexanone reacts with nitrostyrenes in the presence of titanium dichloride diisopropoxide [Ti(Oi-Pr)2Cl2], as shown in Eq. 8.99.157 Endo approach (with respect to the carbocyclic ring) is favored in the presence of Ti(Oi-Pr)2Cl2. Titanium tetrachloride affords the nitronates nonselectively. 

Mukaiyama aldol reactions of aldehydes with silyl enol ethers are amongst the most widely used Lewis-acid-mediated or -catalyzed reactions. However, trimethylsilyl triflate is not active enough to promote these reactions,66 and more active silicon-based Lewis acids have been developed. One example is the species generated by mixing trimethylsilyl triflate (or chloride) and B(OTf)3,319,320 for which the formulation R3Si + [B(OTf)4] is suggested by NMR experiments. Only a catalytic amount of this was needed to complete Mukaiyama aldol reactions of... 

The alkoxycarbenium ions generated by the cation pool method react with various carbon nucleophiles such as substituted allylsilanes and enol silyl ethers to give the corresponding coupling products in good yields. It should be noted that the reactions of alkoxycarbenium ion pools with such nucleophiles are much faster than the Lewis acid promoted reactions of acetals with similar nucleophiles. A higher concentration of the cationic species in the cation pool method seems to be responsible. 

The reactions proceeded efficiently under mild conditions in short time. The silyl enol ethers reacted with the activated acetals or aldehydes at -78 °C to give predominant erythro- or threo-products [136, 137] respectively. In the same manner, the aldol reaction of thioacetals, catalyzed by an equimolar amount of catalyst, resulted in <-ketosulfides [139] with high diastereoselectivity. In the course of this investigation, the interaction of silyl enol ethers with a,]3-unsaturated ketones, promoted by the trityl perchlorate, was shown to proceed regioselec-tively through 1,2- [141] or 1,4-addition [138]. The application of the trityl salt as a Lewis acid catalyst was spread to the synthesis of ]3-aminoesters [142] from the ketene silyl acetals and imines resulting in high stereoselective outcome. 

Silyl enol ethers undergo reaction with carbonyl compounds promoted by Lewis acids, but especially titanium tetrachloride. The reaction is thought to proceed via a titanium chelate which inhibits the reverse aldol process and the regiochemical integrity of the starting silyl enol ether is retained (Scheme 102).373... 

This procedure illustrates a general method for the preparation of crossed aldols. The aldol reaction between various silyl enol ethers and carbonyl compounds proceeds smoothly according to the same procedure (see Table I). Sllyl enol ethers react with aldehydes at -78°C, and with ketones near 0°C. Note that the aldol reaction of sllyl enol ethers with ketones affords good yields of crossed aldols which are generally difficult to prepare using lithium or boron enolates. Lewis acids such as tin tetrachloride and boron trifluoride etherate also promote the reaction however, titanium tetrachloride is generally the most effective catalyst. 

Intramolecular Lewis acid-promoted reaction of coordinated propargylic ether with the silyl enol ether in 158 has been applied successfully to the construction of the highly strained 10-membered cyclic enediyne system 159, present in esperamycin and calicheamycin [39,40]. The enediyne system 157 was prepared by the Pd-catalysed Sonogashira coupling of (Z)-l,2-dichloroethylene (154) with two different terminal alkynes 155 and 156. 

Two extreme pathways may be envisaged for this transformation. One involves a pericyclic reaction followed by desilylation and elimination of methoxide from the product silyl enol ether. The alternative proceeds via a Lewis acid promoted aldol reaction to give an intermediate which cyclizes to the product dihydropyrone (Figure Si3.6). The actual pathway in an individual case is affected to a considerable degree by the nature of the Lewis acid used and lies somewhere between these two extremes. 

Michael reactions. This system promotes a Michael addition of silyl enol ethers to a,(3-unsaturated thiolesters, which are excellent Michael acceptors. Trityl salts are less effective, as are Lewis acids in combination with SnCl2. 

Whereas methyl 2-siloxycyclopropanecarboxylates are thermally stable up to temperatures as high as 170 °C, they readily rearrange at low temperatures under the influence of appropriate Lewis acids. Catalytic amounts (0.05-0.4 equiv.) of iodo-trimethylsilane within minutes to days promote a quantitative ring opening of cyclopropanes 755 to the corresponding silyl enol ethers 156 (Eq. 68, Table 4)88). 

Since the Lewis acid-promoted reactions of the oxidized products with nucleophiles give the corresponding N-acyl-a-substituted amines efficiently, the present reactions provide a versatile method for selective C-H activation and C-C bond formation at the a-position of amides [138]. Typically, TiCl4-promoted reaction of a-t-butyldioxypyrrolidine 66, which can be obtained by the ruthenium-catalyzed oxidation of l-(methoxycarbonyl)pyrrolidine with f-BuOOH, with a silyl enol ether gave keto amide 67 (81%), while the similar reaction with less reactive 1,3-diene gave a-substituted amide 68 (Eq. 3.80). 

The Mukaiyama aldol reaction of carbonyl substrates with silyl enol ethers is the most widely accepted of Lewis acid-promoted reactions. Many Lewis acids for the reaction have been developed and used enantioselectively and diastereoselectively. In 1980, catalytic amounts of la were found by Noyori et al. to effect aldol-type condensation between acetals and a variety of silyl enol ethers with high stereoselectivity [2c,20]. Unfortunately, la has poor Lewis acidity for activation of aldehydes in Mukaiyama s original aldol reaction [21]. Hanaoka et al. showed the scope and limitation of 11-cat-alyzed Mukaiyama aldol reaction, by varying the alkyl groups on the silicon atom of silyl enol ethers [22]. Several efforts have been since been made to increase the reactivity and/or the Lewis acidity of silicon. One way to enhance the catalyst activity is to use an additional Lewis acid. 

The la-promoted imino Diels-Alder reaction is highly susceptible to the Lewis acid employed and to the structure of substrates. iV-Phenyl aromatic aldimine 34 readily cyclizes with the silyl enol ether of 35 under the influence of 10 mol % Ic to give exo adduct 36 exclusively (Sch. 26), whereas up to 98 % endo selectivity is observed when AICI3 is used at 20 °C [55a]. 

The Lewis acid-catalyzed conjugate addition of silyl enol ethers to a,y3-unsaturated carbonyl derivatives, the Mukaiyaraa Michael reaction, is known to be a mild, versatile method for carbon-cabon bond formation. Although the development of catalytic asymmetric variants of this process provides access to optically active 1,5-dicarbonyl synthons, few such applications have yet been reported [108], Mukiyama demonstrated asymmetric catalysis with BINOL-Ti oxide prepared from (/-Pr0)2Ti=0 and BINOL and obtained a 1,4-adduct in high % ee (Sch. 43) [109]. The enantioselectiv-ity was highly dependent on the ester substituent of the silyl enol ether employed. Thus the reaction of cyclopentenone with the sterically hindered silyl enol ether derived from 5-diphenylmethyl ethanethioate proceeds highly enantioselectively. Sco-lastico also reported that reactions promoted by TADDOL-derived titanium complexes gave the syn product exclusively, although with only moderate enantioselectiv-ity (Sch. 44) [110]. 

Kobayashi et al. studied the catalytic activity of many metal salts in Mukaiyama-aldol reactions in aqueous THE They came to the conclusion that the catalytic activity of a metal in aqueous media should be related both to the hydrolysis constant, /Ch, and water exchange rate constant (WERC) of the metal [8]. All metals with good catalytic activity had p/Ch values ranging between 4.3 and 10.08 and WERC > 3.2 X 10 s This was because when for a metal is < 4.3, the metal cation is readily hydrolyzed to generate oxonium ion, which then helps the decomposition of the silyl enol ethers. When pMh > 10.08 the Lewis acidity of the metal is too low to promote the reaction. When the WERC is < 3.2 x 10 m s, exchange of water molecules seldom occurred and aldehydes had a very little chance to coordinate to the metal to be activated. The metals which fulfill these criteria are Sc(III), Fe(II), Cu(II), Zn(ll), Y(IIl), Cd(Il), Ln(Ill) and Pb(ll). 

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