Vinyl ethers deprotonation

Different rate-determining steps are observed for the acid-catalyzed hydration of vinyl ethers (alkene protonation, ks kp) and hydration of enamines (addition of solvent to an iminium ion intermediate, ks increasing stabilization of a-CH substituted carbocations by 71-electron donation from an adjacent electronegative atom results in a larger decrease in ks for nucleophile addition of solvent than in kp for deprotonation of the carbocation by solvent. 

Accurate values of these acidities are not known experimentally because these compounds are in the weakly acidic range, but some qualitative conclusions can be made. For example, on bombardment of butadiene or methyl vinyl ether with NIR, the corresponding deprotonated anions (R ) were present but not in the case of tert-butylethylene. Butadiene and methyl vinyl ether are therefore more acidic than tert-butylethylene. The... 

An ab initio study of the energetics of deprotonation of cyclic vinyl ethers by organolithium reagents has clarified the ring-size-dependent competition between vinylic and allylic deprotonation.The respective transition states involve preequilibrium complexation of lithium to the electron-rich vinyl ether oxygen, prior to deprotonation via a multi-centre process free ions are not formed during the lithiation. 

Metalated vinyl ethers are configurational stable up to —20°C in tetrahydrofuran. H-NMR measurements of 1-ethoxy-1-lithioethene TMEDA did not show any coalescence of the signals for the vinyl protons until the onset of decomposition. Thus, there is no evidence of inversion in this case . Similar configurational stability is displayed by a-lithiated thioethers in tetrahydrofuran no inversion occurs up to 0°C. On the contrary, deprotonated vinyl sulfoxides and sulfones are configurationally less stable . ... 

Enhanced acidity also characterizes the sp -carbon bonded hydrogen compared to the sp one. As a consequence, alkyl vinyl ethers are more acidic than dialkyl ether and thus can be deprotonated more easily. 1-Ethoxy-1-lithioethene 54252-254 gener-... 

Whereas carbenoid character is definitely present in metalated alkyl vinyl ethers, lithiated alkyl and aryl vinyl sulfides and thioesters, which are easily available by hydrogen-lithium exchange, do not display carbenoid-typical reactions . They rather behave like nucleophilic reagents, so that their discussion is beyond the scope of this overview despite their utility in synthesis The same appiies to various derivatives of enamines, deprotonated in the vinyiic a-nitrogen position - . 

TABLE 6. Representative examples of a-lithiated vinyl ethers, generated by deprotonation, and reactions with electrophiles... 

The metalation of vinyl ethers, the reaction of a-lithiated vinyl ethers obtained thereby with electrophiles and the subsequent hydrolysis represent a simple and efficient method for carbonyl umpolung. Thus, lithiated methyl vinyl ether 56 and ethyl vinyl ether 54, available by deprotonation with t- or n-butyllithium, readily react with aldehydes, ketones and alkyl halides. When the enol ether moiety of the adducts formed in this way is submitted to an acid hydrolysis, methyl ketones are obtained as shown in equations 72 and 73 . Thus, the lithiated ethers 56 and 54 function as an acetaldehyde d synthon 177. The reactivity of a-metalated vinyl ethers has been reviewed recently . 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

Meyers and Shimano discovered the unusual deprotonation behavior of ethoxy-vinyllithium-HMPA complex (EVL-HMPA) for the deprotonation of the trans-oxazoline 366 and the cw-oxazoline 367. The EVL-HMPA complex is prepared by deprotonation of ethyl vinyl ether with ferf-butyllithium in THE followed by addition of HMPA. Reaction of the frani-oxazoline 366 with both the EVL-HMPA complex and conventional alkyllithium reagents (RLi) resulted in deprotonation at the benzylic 5-position. In contrast, deprotonation of 367 occurred at the 4-position with an alkyllithium reagent RLi, whereas benzylic deprotonation predominated with the EVL-HMPA complex (Scheme 8.117). ° The authors proposed that EVL-HMPA complexes with the 5-phenyl substituent prior to deprotonation. 

Cyclic vinyl ethers have been deprotonated using f-butyllithium in THF (77TL4187). The carbanions formed, which react readily with a variety of electrophiles, constitute a special type of protected acyl anion. Compound (658), available from the metallated pyran (657) and methallyl bromide, gave the /8-vinyl enone (659) on hydrolysis and cyclization (Scheme 152). 

Treatment of some iron-acyl complexes with trifluoromethanesul-phonic anhydride (TfzO) affords vinylidene derivatives directly (5 7,38). The reaction is envisaged as a nucleophilic attack on TfzO by the acyl, followed by deprotonation to the vinyl ether complex. A combination of an excellent leaving group (TfO-) with a good electron-releasing substituent on the same carbon atom facilitates the subsequent formation of the vinylidene ... 

When the anisolium complex generated by the addition of MVK to the 2-methoxytetra-hydronaphthalene complex 59 is utilized in the above cyclization sequence, the tricyclic oxonium complex 61 is generated (Scheme 6). Deprotonation of 59 with pyridine forms the extended vinyl ether complex 60, which cydizes and eliminates water to form 61 when exposed to TBSOTf. Hydrolysis of 61, followed by oxidation of the metal fragment, yields the dienone 62 in 15 % yield (based on 59). 

If an [Os]-anisolium complex bears a proton at C4 (63, Scheme 7), exposure to DIEA at low temperature results in a kinetic deprotonation of the benzylic carbon attached to C3 generating the extended vinyl ether 64. This complex cyclizes under Lewis addic conditions to generate an anisolium ion, which can then be deprotonated at C4 to generate a tetralin complex [25]. Heating this species liberates the tetralin 65 in 39 % yield (based on 63). 

The presence of a heterosubstituent facilitates deprotonation. 4-Methyl-4H-pyran and 1,4-dimethyldihydropyr-idine are regioselectively metallated at the position next to the heteroatom by LIC-KOR or trimethylsilylmethylpotassium.47 The metallation of cyclic vinyl ethers with Schlosser s base has been successfully used in the synthesis of C-glycosides48 50 via metallation of the glucal followed by a reaction with tributyltin chloride to afford the corresponding tin derivative that could be submitted to coupling reactions with various electrophiles.48... 

Deprotonation of a vinyl ether. The enol ether 1 is deprotonated selectively at the p-position by sec-BuLi at — 78°. The anion reacts with alkyl iodides under Cul and HMPT catalysis and also with aldehydes and ketones. Only one geometrical isomer, presumed to be (Z), is isolated in all cases. 

OL-MethoxyvinyUithium. Details are available for deprotonation of methyl vinyl ether by r-butyllithium to provide a-methoxyvinyllithium (a), a useful acyl anion equivalent. Thus a reacts with ClSilCHj), to provide I-(methoxyvinyl)trimethylsilane (1), a useful precursor to acetotrimethylsilane (2). 

Several groups have completed computational studies on the relative stabilities of osmium carbyne, carbene, and vinylidene species. DFT calculations on the relative thermodynamic stability of the possible products from the reaction of OsH3Cl(PTr3)2 with a vinyl ether CH2=CH(OR) showed that the carbyne was favored. Ab initio calculations indicate that the vinylidene complex [CpOs(=C=CHR)L]+ is more stable than the acetylide, CpOs(-C=CR)L, or acetylene, [CpOs() -HC=CR)L]+, complexes but it doesn t form from these complexes spontaneously. The unsaturated osmium center in [CpOsL]+ oxidatively adds terminal alkynes to give [CpOsH(-C=CR)L]+. Deprotonation of the metal followed by protonation of the acetylide ligand gives the vinylidene product. 

Silylketene 0-acetals can also be general from allyl A -phenylimidates by deprotonation and subsequent -silylation. Predominant (Z)-configuration of the vinyl ether double bond in (96) leads, under the assumption of a chair transition state, with allylimidates (95a-d) preferentially to anti-products... 

Eichinger, P. C. H., Bowie, J. H. Gas-phase carbanion rearrangements. Does the Wittig rearrangement occur for deprotonated vinyl ethers J. Chem. Soc., Perkin Trans. 2 1990, 1763-1768. 

The nucleophilicity of sulfur and its ability to stabilize a-carbanions provide sulfur compounds with unique opportunities for sigmatropic processes consecutive rearrangements are no exception. The formation of salt (140) via Sn2 alkylation of ( )-2-butenyl bromide (139) followed by deprotonation leads to the intermediate allyl vinyl ether (141) which, under the conditions of the deprotonation, undergoes a thio-Claisen rearrangement to afford thioamide (143 Scheme 10). Thermolysis of (143) at elevated temperature affords the Cope product (142) in addition to some of its deconjugated isomer. Several unique characteristics of the thio-Claisen sequence should be noted first, the heteroatom-allyl bond is made in the alkylation step, this connection teing not notrtudly practised in the parent Claisen reaction ... 

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