Vinyl ketene silyl acetals

In aldol reactions, especially Mukaiyama aldol reactions, TiIV compounds are widely employed as efficient promoters. The reactions of aldehydes or ketones with reactive enolates, such as silyl enol ethers derived from ketones, proceed smoothly to afford /3-hydroxycarbonyl compounds in the presence of a stoichiometric amount of TiCl4 (Scheme 17).6, 66 Many examples have been reported in addition to silyl enol ethers derived from ketones, ketene silyl acetals derived from ester derivatives and vinyl ethers can also serve as enolate components.67-69... 

No reaction occurs with vinyl ethers, silyl enol ethers, or ketene silyl acetals, usually used in thermal [2 + 2]cycloaddition reactions, but the present case is the first example of the preparation of a chiral cyclobutanone by a cycloaddition route. 

Unfortunately, attempts to perform this substitution reaction on cyclohexenol and geraniol led to the exclusive formation of the corresponding silyl ethers. It thus would seem that one requirement for effective carbon-carbon bond formation is that allylic alcohols be secondary and have possess y,y-disubstitution. Pearson, however, discovered a method with less restriction on the natiue of the substrate he used allylic acetates with y-mono-substitution or primary alcohols [96]. Not only ketene silyl acetals but also a diverse set of nucleophiles including aUyl silane, indoles, MOM vinyl ether, trimethylsilyl azide, trimethylsilyl cyanide, and propargyl silane participate in the substitution of y-aryl allylic alcohol 90 to give allylated 91 (Sch. 45). Further experimental evidence suggests that these reactions proceed via ionization to allylic carboca-tions—alcohols 90 and 92 both afforded the identical product 93. 

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... 

The fused salt CsOH-CsF acts as a desilylating reagent on ketene silyl acetals to give the equivalent enolate. The reaction proceeds at -60 °C. The equivalent reaction with methyl vinyl ketone proceeds by 1,4-addition (Scheme 2.32) [22]. 

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. 

Unsaturated acyl oxazolidinones 1 undergo enantiospecific [2 + 2] cycloadditions with 1,1-di-methylthioethylene and a catalyst consisting of a 1 1 mixture of diisopropoxytitanium dichloride and the chiral diol 243,44. The cyclobutane 3 is obtained in excellent yield with high enantiomeric excess. This is the first example of the enantiospecific [2 + 2] cycloaddition yielding a cyclobutane using an external chiral auxiliary as a chiral catalyst. Unfortunately, the scope of this reaction is quite limited since it fails with vinyl ethers, silyl enol ethers and ketene silyl acetals. 

As an extension of this work, these authors have applied this catalyst system to vinylogous asymmetric Mukaiyama-type aldol reactions, involving silyl vinyl ketene acetals and pyruvate esters. These reactions afforded the corresponding y,5-unsaturated a-hydroxy diesters with quaternary centres in high yields and enantioselectivities of up to 99% ee (Scheme 10.25). It was shown that the presence of CF3CH2OH as an additive facilitated the turnover of the catalyst. 

The reactions of nitroalkenes (42) with various enols (43b) (vinyl ethers, silyl, and acyl enolates, ketene acetals) have been studied in most detail (110, 111, 125—154). As a mle, these reactions proceed smoothly to give the corresponding nitronates (35f) in yields from high to moderate. As in the reactions with enamines, the formation of compounds (44b) is attributed to the ambident character of the anionic centers in zwitterionic intermediates analogous to those shown in Scheme 3.43. 

A catalytic enantio- and diastereo-selective aldol reaction of ketones with ketene (g) silyl acetals, H2C=C(OTMS)-OMe, gives fair to good yields and ee.129 With further substitution of the vinyl function, the reaction is diastereoselective, up to 97%. A highly developed catalyst/promoter protocol is employed a copper fluoride complex is combined with a Taniaphos auxiliary (a chiral ferrocenyldiphosphine), plus (EtO)3SiF. Evidence for the formation of species (EtO)4 SiF (n > 2) as active... 

Later, the dimethylphenylsilyl adduct 75 d was not only converted to the vinyl-ketene acetal 81 by a Wittig-Horner reaction via the ester 80, but also by reduction of 80 to the aldehyde 84 followed by silylation of the corresponding anion to the silylenol ether 85. Vinylcyclohexenes without terminal substitution (e. g., 83) was prepared via an alcohol derived from 80 or 84 [73,74]. The least substituted diene 83 was alternatively prepared from the triflate 82 in a Stille coupling with trialkylvinyl stannane [75] (Scheme 24), a reaction also used by Toshima etal.[76]. 

A wide range of olefins can be cyclopropanated with acceptor-substituted carbene complexes. These include acyclic or cyclic alkenes, styrenes [1015], 1,3-dienes [1002], vinyl iodides [1347,1348], arenes [1349], fullerenes [1350], heteroare-nes, enol ethers or esters [1351-1354], ketene acetals, and A-alkoxycarbonyl-[1355,1356] or A-silyl enamines [1357], Electron-rich alkenes are usually cyclopropanated faster than electron-poor alkenes [626,1015],... 

Triazines are generally more reactive in [2 + 4] cycloaddition in comparison with 1,2,3-tria-zines. The wide variety of dienophiles can be employed enamines, enaminones, vinyl silyl ethers, vinyl thioethers, cyclic ketene jV,O-acetals, /V-phenylmaleimide, 6-dimethylaminopentafulvene, 2-alkylidene-imidazolidines (cychc ketene aminals), cyclic vinyl ethers, arynes, benzocyclopropene, acetylenes, and alkenes like ethylene, (Z)-but-2-ene, cyclopentene, cyclooctene and bicyclo[2.2.1]hept-2-ene, hexa-1,5-diene, cycloocta-1,5-diene, diallyl ether, cyclododeca-l,5,9-triene,... 

Vinyl sulfoxides (221), which are aldehyde a-cation equivalents, and vinylthiolium ions (230), which are a.jj-unsaturated carbonyl 3-cation equivalents, are also suitable acceptors for silyl ketene acetals and enol silyl ethers (Scheme 36). Kita reports that the bulky r-butyldimethylsilyl ketene acetals and tri-methylsilyl ketene acetals form 1 1 adducts (224) and 1 2 adducts (225) with (221), respectively 91 mechanistically, these additions proceed via an initial Pummerer rearrangement The vinylthiolium ion additions are notable for their synthetic flexibility for example, additions to the ketene dithioacetal (229) proceed with higher diastereoselectivity than the corresponding enolate additions to a,3-unsaturated esters.9 lc,91d... 

As shown in Scheme 1, GTP converts methacrylate monomer to a polymer with one end group corresponding to the R on the initiator and the other end a trimethylsilyl ketene acetal. If the initiator contains a vinyl group not reactive to GTP, a macromonomer results [8]. The silyl ketene acetal end can be used to initiate another monomer, for example butyl methacrylate, to give... 

This gentle variant of the Claisen Rearrangement employs the allyl ester of a carboxylic acid instead of an allyl vinyl ether. The ester is converted to its silyl-stabilized enolate (silyl ketene acetal), which rearranges at temperatures below 100 °C. 

Treatment of chiral, nonracemic vinyl sulfoxides (214) with O-silylated ketene acetal (215) in the presence of a catalytic amount of zinc chloride resulted in an enantioselective additive Pummerer-type reaction, affording the corresponding enantiomerically enriched methyl-4-siloxy-4-sulfenylbuyrate (216) (Scheme 55).122 This is the overall addition of the enolate equivalent to the vinyl sulfoxide. 

---