Hydroxy enol ethers

Aldehydes and ketones RCOR react with oc-methoxyvinyllithium CH2= C(Li)OMe to give hydroxy enol ethers RR C(OH)C(OMe)=CH2, which are easily hydrolyzed to acyloins, RR C(OH)COMe. this reaction, the CH2=C(Li)OMe is a synthon for the unavailable H3C—C=0. The reagent also reacts with esters RCOOR to give RC(OH)(COMe=CH2)2- A synthon for the Ph—C=0 ion is PhC(CN)OSiMe3, which adds to aldehydes and ketones RCOR to give, after hydrolysis, the a-hydroxy ketones, RR C(OH)-COPh. °... 

This intramolecular hydrosilylation can be extended to a-hydroxy enol ethers (2-alkoxy-l-alkene-2-ols) to provide access to 2,3-sy -l,2,3-triols.2 In this case a neutral catalyst, Pt(0)-vinylsiloxane,3 is preferred over H2PtCl6. 

Regio- and Stereoselective Intramolecular Hydrosilation of a-Hydroxy Enol Ethers 2,3-syn-2-Methoxymetnoxy-1,3-nonanediol. 

Aldehydes and ketones RCOR react with a-methoxyvinyllithium CH2=C(Li)OMe to give hydroxy enol ethers RR C(OH)C(OMe)=CH2, which are easily hydrolyzed to acy-loins RR C(OH)COMe.597 In this reaction, the CH2=C(Li)OMe is a synthon for the un-... 

Tamao, K. Nakagawa, Y. Ito, Y. Regio- and stereoselective intramolecular hydrosilylation of a-hydroxy enol ethers 2,3-syn-2-methoxy-methoxy-l,3-nonanediol. Org. Synth. 1998,... 

A useful synthetic alternative to the Mukaiyama aldol addition is the carbonyl-ene reaction [17], This reaction of an aldehyde 51 with an enol ether 55, bearing at least one hydrogen atom in the allylic position, under Lewis-acid catalysis, yields a ff-hydroxy-enol ether of type 56 (Scheme 10). By use of a chiral Lewis acid (L ) enantioselectivity can be achieved. For the... 

REG 10- AND STEREOSELECTIVE INTRAMOLECULAR HYDROSILYLATION OF a-HYDROXY ENOL ETHERS 2,3-syn-2-METhOXYM ETHOXY-1,3-NON ANEDIOL (1,3-Nonanedlol, 2-(methoxymethoxy)-, (R, R )-( )-)... 

Straightforward is the stereoselective introduction of two oxygen functionalities onto carbon-carbon double bonds, as represented by the Sharpless epoxidation4 or osmium tetroxide oxidation of allyl alcohols.5 An alternative route may be envisioned by anti-Markovnikov hydration of enol ether derivatives, as in the present method, but such an approach has so far been rarely studied. The only other reported method is hydroboration which affords syn/anti ratios in the range of 83/17 to 3/97 in essentially the same systems as those examined in this procedure. The method described here is a highly stereoselective route to 2,3-syn isomers of 1,2,3-triol skeletons from a-hydroxy enol ethers. 

This procedure consists of the synthesis of a precursor, methoxymethyl vinyl ether, an a-hydroxy enol ether, and the intramolecular hydrosilylatlon of the latter followed by oxidative cleavage of the silicon-carbon bonds. The first step, methoxymethylation of 2-bromoethanol, is based on Fujita s method.7 The second and third steps are modifications of results reported by McDougal and his co-workers. Dehydrobromination of 2-bromoethyl methoxymethyl ether to methoxymethyl vinyl ether was achieved most efficiently with potassium hydroxide pellets -9 rather than with potassium tert-butoxide as originally reported for dehydrobromination of the tetrahydropyranyl analog.10 Potassium tert-butoxide was effective for the dehydrobromination, but formed an adduct of tert-butyl alcohol with the vinyl ether as a by-product in substantial amounts. Methoxymethyl vinyl ether is lithiated efficiently with sec-butyllithium in THF and, somewhat less efficiently, with n-butyllithium in tetrahydrofuran. Since lithiation of simple vinyl ethers such as ethyl vinyl ether requires tert-butyllithium,11 metalation may be assisted by the methoxymethoxy group in the present case. 

REGIO- AND STEREOSELECTIVE INTRAMOLECULAR HYDRO-SILYLATION OF a-HYDROXY ENOL ETHERS 2,3-syn-2-METHOXY-METHOXY-1,3-NONANEDIOL... 

In an extension of this process, the intramolecular hydrosilylation of a-hydroxy enol ethers has been presented as a new, syn selective route to 1,2,3-triols (Scheme 11). With such sensitive substrates, a neutral hydrosilylation catalyst, Pt [(CH2==CH)Me2Si]20 2, must be used. The utility of this method has been demonstrated in a synthesis of the pentitols, o-arabinol and xylitol (as their pentaacetates), in optically pure form. 

Cyclic acetals can be prepared by halocyclization of hydroxy enol ethers. This reaction proceeds in dichloromethane at 0°C when IV-bromosuccinimide is used as the halonium source. Yields are high while the stereoselectivity depends on the enol ether configuration. Thus, starting from (Z)-l, a unique product 2A is isolated in 87% yield. In 2A the methoxy group lies in the equatorial position, as determined by H-NMR evidence. On the contrary, from the ( )-isomer, a 60 40 diastereomeric mixture is obtained in 81 % yield. In this case, the major product 2B has the methoxy group in the axial position39. 

The cydization of the hydroxy enol ether 5, performed with trifluoroacetic acid in benzene, leads to a single spiroacetal 6. On the other hand, when treated with acetic acid in benzene, 5 gives an equimolar mixture of spiroacetals 6 and 7. It is worth mentioning, however, that on treatment with trifluoroacetic acid this mixture leads exclusively to 6. These results show that the cydization, performed with either acetic acid/benzene or trifluoroacetic acid/benzene, proceeds under kinetic or thermodynamic control, respectively152. 

The method has now been used to synthesize 9,10-dimethyl-trarcs-l-decalones,11 which have the characteristic C/D ring system of pentacyclic triterpenes. Thus i ruction of the hydroxy enol ether (9) with the Simmons-Smith reagent gives the cyclopropyl ether (10). Cleavage with 7% methanolic hydrochloric acid leads to the hydroxy ketone (11), convertible by Wolff-Kishner reduction followed by oxidation into (12). 

A process for the asymmetric cyclopropanation of the enol ethers of cyclic and acyclic ketones has been developed by Tai [109-111]. In this process, a 2-symmetric acetal is isomerized to a hydroxy enol ether which serves as substrate or the Simmons-Smith cyclopropanation, as shown in Scheme 6.29. The stereoselectivity is nearly perfect, but a mechanistic hypothesis has not been proposed. The auxiliary may be removed either by hydrolysis, to give the methyl ketone, or by oxidation of the alcohol and p-elimination [111]. 

Stevens and co-workers have also attempted to develop a fundamentally different approach to the tricyclic amino ketone 463 which is used in the Fischer cyclization approach to the Aspidosperma skeleton (240). Condensation of the aldehyde-ester 553 with protected keto amine 554 gave an imine (555) which, upon heating with ammonium chloride at 160°, afforded the 2-pyrroline ester 556 in 70% yield. Treatment with dry hydrochloric acid gas in ether was followed by acid hydrolysis of the ketal, and base-catalyzed cyclization produced a mixture of two enol ethers (557 and 558) the latter predominating. The major isomer was reduced with lithium aluminum hydride and the hydroxy enol ether dehydrated in hot... 

Oxidation of chiral ketals The chiral ketal 1 is oxidized by Rc207 and 2,6-lutidinc to 2-hydroxy ketal 2 with high (>99 1) enantioselectivity. This reaction is believed to proceed via a perrhenate ester of a 2-hydroxy enol ether, since the 2-hydroxyethyl enol ether 3 is oxidized to the 2-hydroxy ketal 2 by RcaOy in similar enantioselectivity and comparable yield. 

Extremely high stereoselectivity has been attained in the intramolecular hydrosilation of a-hydroxy enol ethers, leading to 1,2,3-triol derivatives with 2,3-syn stereochemistry (eq 4). It has been pointed out, however, that the stereoselectivity largely depends upon the nature of the catalyst, Pt or Rh, and the presence or absence of the disilazane in the Pt case (eq 5). ... 

General Discussion. (Z)-(Trimethylsilyloxy)vinyllithium (1) has essentially been used for a one-pot vinylogation of carbonyl compounds. Condensation of (1) with aldehydes and ketones (2) occurs readily at low temperature (—70 °C) then treatment of the reaction mixture with an acidic solution in mild conditions (IN hydrochloric acid, 0 °C to rt) produces the Q ,/3-unsaturated aldehydes (3), without double bond migration. The ( 0 isomers are obtained alone (from aldehydic compounds) or very predominantly (fromketonic compounds). The intermediate adducts, y-hydroxy enol ethers (4), can be isolated by slightly basic mild hydrolysis (eq l).l... 

Extremely sterically demanding Br0nsted acid catalyst 13 indeed efficiently catalyzed the asymmetric conversion of small and further unfunctionalized hydroxy enol ether substrates. Various spiroacetals were obtained with high enantios-electivity independent of the ring size of the enol ether by the formation of either 6- or 5-membered rings (Table 4) [57]. Catalyst 13 also enabled the first catalytic asymmetric synthesis of the natural product olean (entry 2). AU these small spiroacetals in Table 4 are core stmcmres of many natural products [6-8]. 

Addition of tributylstannyl-lithium to crotonaldehyde and protection of the resulting alcohol with chloromethyl methyl ether gives the stannane (192), which reacts with both alkyl and aryl aldehydes RCHO to form specifically the t/rr o-hydroxy-enol ethers (193). These latter compounds have been used to prepare tra/i5-4,5-disubstituted butyrolactones by hydrolysis and subsequent oxidation. Palladium-catalysed carbonylation of RX in the presence of organotin species constitutes a useful synthesis of unsymmetrical ketones, and in the example reported this year RX is an arenediazonium salt. The reaction, which is basically an aromatic acylation, proceeds in good to excellent yield. Another Pd-catalysed reaction of aromatics, this time aryl bromides, is their reaction with acetonyltributyltin (194), prepared from methoxytributyltin and isopropenyl acetate, to give the arylacetones (195). ... 

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