Ketene alkyl silyl acetals, reactions

Ketene alkyl silyl acetals may also be used as nucleophiles for the formation of 0-hydroxy esters. The present reaction can be carried out equally well on large or small (mmole) scales. For small scale applications,... 

Cyclopropane formation was also observed as a side reaction (1 9 up to 1 1) in the palladium-catalyzed coupling of ketene alkyl silyl acetals with open-chain and cyclic allyl acetates. The reaction is interpreted as proceeding via nucleophilic central attack of a jr-allyl intermediate. Although cyclopropane formation proceeds only with low yields, a highly stereospecific pathway was observed with substituted 3-cyclohexenyl acetates. ... 

In several cases the nucleophilic attack on a n-allylpalladium complex 97 has been observed to occur on the central carbon atom of the allylic moiety. The resulting palladacy-clobutane derivative 98, instead of /3-hydride eliminadon, underwent reductive elimination furnishing a cyclopropane derivative 99. In spite of theoretical predictions which, appear to rule out such reactions, " they have been observed experimentally (Scheme 23). Thus, in the Pd-catalyzed reactions of cyclopropylideneethyl acetate 100 with ketene alkyl silyl acetals 101, the spiropentylacetates 103, albeit in low yield, along with the normal products 102 were observed.With Tj -allylpalladium-pyridinylpyrazole complexes 108 as catalysts this reaction mode of allyl acetates 104 with ketene acetals 105 became predominant so that cyclopropylacetates 106 were obtained as the main products (Scheme 23). An enantioselective version of this cyclopropane formation has also been reported. ... 

Table 1 Prototypical reactions of ketene alkyl silyl acetals...

Mukaiyama-Michael Reactions. 1,4-Addition of ketene alkyl silyl acetals to a./S-unsaturated carbonyl compounds (eq 10) is promoted by a variety of Lewis acids (for example, TiCU, Ti(OR)4, SnCU, trityl perchlorate, lanthanide salts, Al-montmo-rillonite clay), or Lewis bases such as fluoride ion (eq 11), or quaternary ammonium carboxylates. Lanthanide salts are particularly effective catalysts, and in the case of ytterbium(III) tri-fluoromethanesulfonate, the catalyst can be recovered (eq 10). ... 

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]... 

Alkylation of ketene silyl acetals with nitroalkenes has several limitations such as modest yield, lack of generality, and inconveniently low reaction temperatures. Tucker and coworkers have found that sterically encumbered Lewis acids such as MAD give better results than other Lewis acids (Eq. 4.64).83... 

Silyl enol ethers can be dimerized to symmetrical 1,4-diketones by treatment with Ag20 in dimethyl sulfoxide or certain other polar aprotic solvents.465 The reaction has been performed with R2, R-1 = hydrogen or alkyl, though best yields are obtained when R2 = R1 = H. In certain cases, unsymmetrical 1,4-diketones have been prepared by using a mixture of two silyl enol ethers. Other reagents that have been used to achieve either symmetrical or cross-coupled products are iodosobenzene-BFy-EtiO.466 ceric ammonium nitrate,467 and lead tetraacetate.m If R1 = OR (in which case the substrate is a ketene silyl acetal), dimerization with TiCL, leads to a dialkyl succinate (32, R1 = OR).4 9... 

Ikeda, K., Achiwa, K., and Sekiya, M., Tri-fluoromcihanesullbnic acid-promoted reaction of hcxahydro-l,.3,5-triazincs with ketene silyl acetals. Convenient synthesis of alkyl P-aminocaiboxylates. Tetrahedron lelt., 24, 913, 1983. 

A remarkable finding is the sensitivity of this reaction to the substituents of the starting silyl ketene acetals. Reactions of silyl ketene acetals derived from more common ethyl esters are totally stereo-random, and give a mixture of erythro and threo isomers in even ratios with improved chemical yields. In sharp contrast, the use of silyl ketene acetals generated from phenyl esters leads to good diastereo- and enantios-electivity and excellent chemical yields. The reason for this is unclear, but certain secondary interaction between electron-rich silyl ketene acetals derived from alkyl esters and Lewis acid might be responsible. 

The new rert-alkylation method was highlighted by the selective functionalization of difluoroalkane with different reactivity profile including tert-alkyl/pnm-alkyl and tert-alkyl/ ec-alkyl fluorides. This method provides a facile route to new types of orga-nofluorine compounds which are increasingly important in biochemical/biological, pharmacological, and material science [98]. For instance, reaction of difluoroalkane 102 with ketene silyl acetal 99 (R = H, = Me) was catalyzed by 10 mol%... 

Trost and Scanlan reported a Pd-catalyzed condensation of a vinyl epoxide 75 and an allyl sulfone 76 in the presence of dppf under neutral conditions [231]. This alkylation allows a room temperature entry to a basic indolizidine ring system as a step towards the synthesis of (+)-aj//o-Pumiliotoxin 339B [232], The modification of allylic alkylations by condensation of a diene 77 with a pronucleophile 78 also leads to C-C bond formation at the allylic position in both 1 1 (79 and 80) and 2 1 (81 and 82) products [233]. Reactions between ketene silyl acetals 83 with allyl... 

Several routes to this class of compounds have been reported, such as (a) crossed Claisen condensation reactions (50-53) (b) acylation of the anion derived from ethyl fluoroacetate (54) or self-condensation of the anion derived from ethyl bromofluoroacetate (55) (c) electrophilic fluorination of the anion of p-ketoesters (56,57) (d) acylation-hydrolysis of fluoroolefins (58) and (e) acylation of fluorine-containing ketene silyl acetals (Easdon, J.C., University of Iowa, unpublished data). The limitations associated with these methods and the success achieved in the alkylation-hydrolysis of a-fluoro phosphorus ylides prompted us to examine acylation-hydrolysis of these a-fluoro ylides as a general route to 2-fluoro-3-oxoesters. 

Narasaka found that optically enriched oxabicydic substrate 277 bearing a vinyl sulfide moiety reacts with a silyl enol ether or ketene silyl acetal in the presence of a Lewis acid to afford the protected cyclohexenols 278a and 278b, Eq. 175 [18]. The reaction was proposed to occur via a ring-opening and alkylation sequence which is equivalent to overall nucleophilic substitution with retention of configuration. Presumably, the nucleophile attacked the carbocationic intermediate from the exo face, because the methylene-OTIPS substituent was blocking the endo side. 

Other groups that react with chloromethyleneiminium salts include hydroxylamines, hydrazines, oximes, imines, azines, anhydrides, imides and ketene O-alkyl-O -silyl acetal derivatives however, reactions with these compounds have been relatively infrequent. 

A useful entry to functionalised ketene-S,S- acetals is based on the reaction of the alkenyl anion (81) with electrophiles (alkyl and silyl halides, aldehydes). This anion was prepared by bromine-lithium... 

Lewis-acid-promoted alkylations of silylenol ethers and silyl ketene acetals [195] with Co-complexed acetylenic acetals [196] and acetylenic aldehydes [197,198] (Scheme 4-56) also proceed with fair to excellent syn diastereoselectivity, in contrast to the low selectivity reactions of the free acetylenic derivatives [199, 200]. Reactions of the complexed aldehydes with lithium enolates are stereospecific, with (Z)-enolates giving syn selectivity and ( )-enolates anti selectivity [201]. The complementary stereoselectivity of the crossed aldol reactions of free and cobalt-complexed propynals with silyl ketene 0,S-acetals has been elaborated by Hanoaka exclusive syn selectivity is exhibited by the complexes and high anti selectivity is found with pro-... 

Saitoh, A., Morimoto, T. and Achiwa, K. (1997) A phosphorus-containing chiral antidine ligand for asymmetric reactions enantioselective Pd-catalysed allylic alkylation. Tetrahedron Asymmetry, 8, 3567-3570 Saitoh, A., Achiwa, K. and Morimoto, T. (1998) Enantioselective allylic substitutions using ketene silyl acetals catalysed by palladium-chiral atitidine complexes. Tetrahedron Asymmetry, 9, 741-744. 

Both 2- and 3-aryl-P-alanine derivatives have been prepared by the Mukaiyama reaction of imines when catalyzed by titanium tetrachloride. The reaction of ketene silyl acetals with 0-alkyl imines is another source of aryl-substituted P-alanines.20 O-Substituted hydroxylamines (an "0-imine") have been used in this type of reaction. When 4.28 reacted with O-silylketene acetal 4.29, in the presence of... 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

Silyl enol ethers and ketene silyl acetals add to aromatic nitro compounds in the presence of TASF(Me) to give intermediate dihydro aromatic nitronates which can be oxidized with bromine or 2,3-dichloro-5,6-dicyano-l,4-benzoquinone to give a-nitroaryl carbonyl compounds the latter are precursors for indoles and oxindoles. The reaction is widely applicable to alkyl-, halo-, and alkoxy-substituted aromatic nitro confounds, including heterocyclic and polynuclear derivatives (eq 7). 

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