Ketones, reaction with silyl enol ethers

A one-pot reaction between a tryptophan ester, benzotriazole, and 2,5-dimethoxytetrahydrofuran in acetic acid gives the diastereomeric benzotriazolyl tetracycles, 349, in good yield. Substitution of the benzotriazole by reaction with silyl enol ethers and boron trifluoride etherate gives the corresponding ketones 350 and 351, and reaction with allylsilanes gives the corresponding alkenes 352 and 353. If the boron trifluoride etherate is added to the mixture before the silane, elimination of benzotriazole from 349 is also observed (Scheme 83) <1999T3489>. 

Table 12 Mannich-type reaction with silyl enol ethers derived from ketones...

Carbonyl activation and deactivation.1 Aldehydes, but not ketones, undergo aldol condensation with silyl enol ethers at —78° in the presence of dibutyltin bistriflate. In contrast, the dimethyl acetals of ketones, but not of aldehydes, can undergo this condensation (Mukaiyama reaction) with silyl enol ethers at -78° with almost complete discrimination, which is not observed with the usual Lewis-acid catalysts. Thus dibutyltin bistriflate activates aldehydes, but deactivates acetals of... 

Substitution of the acetate group at the C-3 position of the /3-sultam 105 can occur by reaction with silyl enol ethers in the presence of zinc iodide or zinc chloride. When the diazo compound is used, after desilylation with tetrabutyl-ammonium fluoride (TBAF), photochemical cyclization gives the bicyclic /3-sultam 106 as a mixture of two cis/ fra -diastereoisomers. When silyl enol ethers derived from cyclic ketones are used, the substitution product is stabilized by a retro-Michael-type reaction leading to open-chained sulfonamides 107 (Scheme 31) <1997LA1261>. 

The use of Moriarty s hypervalent iodine system vide supra) has been extended to reaction with silyl enol ethers. In this case a more activated electrophile is required and the reactions are carried out with iodosylbenzene in the pres ice of boron trifluoiide etherate. However, yields are only moderate and the process seems less useful than the corresponding ketone/enol application. 

Fluoroalkyl ketones may be employed as the electrophilic partners in condensation reactions with other carbonyl compounds. The highly electrophilic hexafluoroacetone has been used in selective hexafluoroisopropylidenation reactions with silyl enol ethers and silyl dienol ethers, e.g. formation of 1. ... 

Condensation with ketones. The aminals serve as synthetic equivalent of trifluoroacetaldehyde. Thus, its condensation with ketones (catalyzed by aqueous HCl) gives 2-(l-hydroxy-2,2,2-trifluoroethyl) ketones and reaction with silyl enol ethers I catalyzed by ZnCl ) delivers the trifluoroethylidene ketones. 

OrThiocyanato ketones. Oxidation of lead(II) thiocyanate in situ and reaction with silyl enol ethers accomplishes the heterofunctionalization of ketones. 

Reaction with silyl enol ethers. Derivatives from ketones and esters behave to- ards arenediazonium salts according to their relative nucleophilicities. a-Arylation, 9 ketones by a free radical pathway and nonradical a-amination of esters are. bserved. 

The catalytic [2-1-2] cycloaddition reactions are an essential and important tool for the syntheses of cyclobutane derivatives. In particular, the catalytic cycloaddition reactions of silyl enol ethers, which are the most easily prepared ketone equivalents, have been an attractive method for cyclobutane syntheses. A number of catalytic methods that give high stereoselectivities and yields have been developed. Recently, several studies on the synthetic utilization of the [2-1-2] cycloaddition have been reported [43]. Further improvements are required for more practical and large scale syntheses. We look forward to further developments of the [2-1-2] cycloaddition reaction with silyl enol ethers in the near future. 

The Mukaiyama aldol reaction refers to Lewis acid-catalyzed aldol addition reactions of silyl enol ethers, silyl ketene acetals, and similar enolate equivalents,48 Silyl enol ethers are not sufficiently nucleophilic to react directly with aldehydes or ketones. However, Lewis acids cause reaction to occur by coordination at the carbonyl oxygen, activating the carbonyl group to nucleophilic attack. 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

Longifolene has also been synthesized from ( ) Wieland-Miescher ketone by a series of reactions that feature an intramolecular enolate alkylation and ring expansion, as shown in Scheme 13.26. The starting material was converted to a dibromo ketone via the Mr-silyl enol ether in the first sequence of reactions. This intermediate underwent an intramolecular enolate alkylation to form the C(7)—C(10) bond. The ring expansion was then done by conversion of the ketone to a silyl enol ether, cyclopropanation, and treatment of the siloxycyclopropane with FeCl3. 

C-Glucosidation. Reaction of the protected a-D-glucopyranosyl chloride 1 with silyl enol ethers activated with AgOTf results in a-C-glucosyl esters or ketones. 

In addition to the former example, Pandey et al. achieved efficient a-aryla-tion of ketones by the reaction of silyl enol ethers with arene radical cations generated by photoinduced electron transfer from 1,4-dicyanonaphthalene. Using this strategy various five-, six-, seven-, and eight-membered benzannulated compounds are accessible in yields in the range 60-70% [39],... 

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