Enol ethers, addition

Because of thetr electron deficient nature, fluoroolefms are often nucleophihcally attacked by alcohols and alkoxides Ethers are commonly produced by these addition and addition-elimination reactions The wide availability of alcohols and fliioroolefins has established the generality of the nucleophilic addition reactions The mechanism of the addition reaction is generally believed to proceed by attack at a vinylic carbon to produce an intermediate fluorocarbanion as the rate-determining slow step The intermediate carbanion may react with a proton source to yield the saturated addition product Alternatively, the intermediate carbanion may, by elimination of P-halogen, lead to an unsaturated ether, often an enol or vinylic ether These addition and addition-elimination reactions have been previously reviewed [1, 2] The intermediate carbanions resulting from nucleophilic attack on fluoroolefins have also been trapped in situ with carbon dioxide, carbonates, and esters of fluorinated acids [3, 4, 5] (equations 1 and 2)... 

The highest enantioselectivities in the base-catalyzed Michael additions have so far been obtained using achiral bases complexed to chiral crown ethers. The addition of methyl 2,3-dihydro-l-oxo-1//-indene-2-carboxylate (1) to 3-buten-2-one using 4 mol% of a [l,T-binaphthalcnc]-2,2 -diol derived optically active crown ether 3 in combination with potassium AY/-butoxide as the base illustrates this successful method 259 260 It is assumed that the actual Michael donor is the potassium enolate complex of 1 and crown ether 3. 

E)-Enol silyl ethers.1 A new highly stereoselective route to (E)-enol silyl ethers involves addition of CH,Li to silyl ketones substituted at the a -position by a SC6H5 group such as 1. The adduct (a) undergoes a Brook rearrangement and... 

The titanium(IV) chloride-catalyzed conjugate addition of enol silyl ethers (182) to (184) and (189 Scheme 30), and silyl ketene acetals, (191) to (194), to ot, 3-enones is die key feature in various synthetic strategies (Mukaiyama-Michael) (Scheme 31).78 79 In contrast to the earlier described enolate addition... 

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... 

A similar palladium-catalyzed cyclization procedure has recently been developed which involves enol ethers capable of (3-H elimination.373 Significant evidence has been accumulated suggesting that an oxa-ir-allyl complex is not an intermediate in these reactions, but that it is better characterized as an enolate addition to a Pdn-alkene complex.376 377 Synthetic applications of this reaction have also appeared.376-379... 

Use of trimethylsilyl triflate to bring about Piunmeier rearrangement requires the presence of a base such as a tertiary amine (vide supra equations 15 and 26). In some instances, involving attempts to alkylate Pummerer intermediates with silyl enol ethers under such conditions, the base has been found to compete as a nucleophile. In the absence of the silyl enol ether, amine addition can be very efficient. For example, treatment of methallyl phenyl sulfoxide with diisopropylethylamine and trimethylsilyl inflate in dichloromethane (equation 29) at 0 C yields the ammonium triflate indicated in 91% yield. Other tertiary amines which undergo this reaction include niethylamine and Af,Af-diethyltrimethylsiI-amine. In the latter case with allyl phenyl sulfoxide as the substrate and a mildly acidic wotk-up, the Mannich derivative shown in equation (30) can be obtained in 90% yield. ... 

Others [180,260]). In general, enol radical cations may be obtained from either direct oxidation of stable ends or by selective oxidation of the enol tautomer of the keto/enol equilibrium. In addition it has been outlined that enol radical cations offer an access to a-carbonyl radical chemistry. Other enol systems like silyl enol ethers, enol esters and enolates similarly may open up after oxidation the chemistry of a-carbonyl radical or a-carbonyl cation intermediates, whereas enol ether oxidative a-functionalization reactions work by another route. 

In the present context, the term electron rich alkenes refers primarily to enol ethers, enol sulfides, and A-vinylamides or A-vinylamines. Such alkenes are typically much more readily ionizable than are simple alkenes. The conversion of these substrates to the corresponding (highly electron deficient) cation radicals represents a sharp Umpolung. The Diels-Alder additions of tra j -anethole, phenyl vinyl ether, phenyl vinyl sulfide, 1,3-dioxole, and A-methylindole to 1,3-cyclohexadiene have been reported (Scheme 22) [49, 52]. 

Similar information is available for other bases. Lithium phenoxide (LiOPh) is a tetramer in THF. Lithium 3,5-dimethylphenoxide is a tetramer in ether, but addition of HMPA leads to dissociation to a monomer. Enolate anions are nucleophiles in reactions with alkyl halides (reaction 10-68), with aldehydes and ketones (reactions 16-34, 16-36) and with acid derivatives (reaction 16-85). Enolate anions are also bases, reacting with water, alcohols and other protic solvents, and even the carbonyl precursor to the enolate anion. Enolate anions exist as aggregates, and the effect of solvent on aggregation and reactivity of lithium enolate anions has been studied. The influence of alkyl substitution on the energetics of enolate anions has been studied. ... 

The copper-mediated 1,4-addition of alkyl groups to a,P-unsaturated ketones affords regiochemically pure enolate anions (see also Section 7.5) which may be trapped at oxygen with silyl halides, acyl halides, or dialkylcarbonates to provide silyl enol ethers, enol acetates, or enol carbonates, respectively. These can be unmasked at a later stage by reaction with MeLi to regenerate the enolate for further elaboration. ... 

Copper-, rhodium-, palladium-, and ruthenium-catalyzed cyclopropanation with diazoacetic esters is possible for a wide range of electron-rich alkenes, including alkylated acyclic alkenes, cycloalkenes, styrenes, 1,3-dienes, enol ethers, enol acetates, and ketene acetals (examples are given in this section, in Houben-Weyl Vol.E19b, ppl099-1155 and in refs 2, 152, 155 and 184). Furthermore, the construction of cyclopropanes with additional strain is possible, for example ... 

Lithium cyclohexadienolates, generated from the corresponding cyclohexenones with lithium diisopropylamide (method A) or produced without using amines from the trimethylsilyl enol ethers, undergo addition to 2-chloro-2-cyclopropyUdeneacetates at ambient temperature in an inert solvent to give y-oxo esters in good to excellent yield (see Table 5). These products can be readily transformed to multifunctional bicyclo[2.2.2]octanes 31 as well as bicyclo[3.2.1]octane derivatives 32. ... 

The Mukaiyama version of the aldol reaction is well known a carbonyl-titanium tetrachloride complex reacts with a trimethylsilyl enol ether. Under these conditions there is no titanium enolate involved. Another procedure has been reported a trimethylsilyl enol ether reacts with titanium tetrachloride to give the titanium enolate addition of the carbonyl compound generates the aldol product (although with slightly lower diastereoselectivity than with Mukaiyama s procedure). (Z)-Enolsilanes from acyclic ketones react rapidly and stereospecifically with TiCU to form (Z)-configured CbTi enolates, while the ( )-isomers react slowly to afford low yields of mixtures of ( )- and (Z)-Cl3Ti enolates (Scheme 41). 

Seebach s topological rule suggesting a preference of synclinal donor/acceptor orientations in a Newman projection along the forming bond cf. Figure 5.8, [60]). For ZfOj-enolates, additional stabilization can be had by metal chelation with the ether oxygen cf. Figure 6.4d). 

An interesting study reports carbene additions to the androstane enol ether (139). Addition of dibromo- and dichloro-carbene gave the D-homo-a-halo-genoenones (140a) and (140b), respectively. The Simmons-Smith reaction on (139) afforded the l6a,17a-cyclopropyl steroid (141). Whereas treatment of (141) with acid provided the D-homo-derivative (142), reaction with iodine, followed by... 

In another example, addition of phenyl vinyl selenoxide into a mixture of an indanedione, hexamethyldisilazane, and TMSCl in dichloromethane affords the a-trimethylsiloxyselenide in 70% yield (eq 67). The reaction proceeds through a sequence of in situ formation of TMS silyl enol ether, Michael addition onto the phenyl vinyl selenoxide, and seleno Pummerer rearrangement of the resulting selenoxide. Trifluoroacetic anhydride and various other trialkylchlorosilanes give the same product for this reaction, but in much lower yields. 

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