Enol ethers from alcohols

Trimethylsilylation of enolizable carbonyl compounds and alcohols has also been accomplished by the fluoride ion promoted reaction with hexamethyldisilane and ethyl trimethylsilylacetate [48, 49], with high stereospecificity giving Z-enol ethers from ketones [50]. l-Trimethylsilyl-(l-trimethylsilyloxy)alkanes, produced from the reaction of aldehydes with hexamethyldisilane, undergo acid-catalysed hydrolysis during work up to yield the trimethylsilylcarbinols [51]. In the case of aryl aldehydes, the initially formed trimethylsiloxy carbanion produces the pinacol (Scheme 3.1). 

ACETYLENIC ETHERS FROM ALCOHOLS AND THEIR REDUCTION TO Z-AND E-ENOL ETHERS PREPARATION OF 1-MENTHOXY-1-BUTYNE FROM MENTHOL AND CONVERSION TO (Z)-AND (E)-1-MENTHOXY-1 -BUTENE ([Cyclohexane, 2-(1 -butynyloxy)-4-methyl-1 -(1 -methylethyl)- [1S-(1a,2p,4p)]-], end [[[Cyclohexane, 2-(1-butenyloxy)-4-methyl-1-(1-methylethyl)-, [1S-[1a,2P(Z),4p]]- and [lS-[1 ,2p(E),4P]]-)... 

ACETYLENIC ETHERS FROM ALCOHOLS AND THEIR REDUCTION TO Z- AND E-ENOL ETHERS PREPARATION OF 1-MENTHOXY-1-BUTYNE FROM MENTHOL AND CONVERSION TO (Z)- AND (E)-1 -MENTHOXY-1 -BUTENE... 

Acetylenic Ethers from Alcohols and Their Reduction to Z- and E-Enol Ethers Preparation of 1-Menthoxy-1-butyne from Menthol and Conversion to (Z)- and (E)-1-Menthoxy-1 -butene. 

It is now known that tiisdkyl phosphates will indeed alkylate I enols. The idea has been extended to the production of methyl ethers from alcohols and trimethyl phosphate, and of a butyl ether according to the equation... 

Formation of ketals (and, in some cases, enol ethers) from ketones by treatment with the chosen alcohol or diol, ethyl orthoformate, and activated montmorilIonite. Yields 32-100%. 

Methoxy-S-thiacyclohexene has been suggested as a potentially useful alcohol-protecting group applicable in nucleotide synthesis. " Ac als are formed from the above enol ether and alcohols in the usual manner and are hydrolysed back to the alcohols with tm = 2 min. in O.OIM-HCI, 4 1 aqueous dioxan at 20 "C. The protecting group can be made more stable to acid by oxidation of the sulphide to sulphone the retardation of the hydrolysis rate was approximately 2x 10. ... 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

Hydroperoxides have been obtained from the autoxidation of alkanes, aralkanes, alkenes, ketones, enols, hydrazones, aromatic amines, amides, ethers, acetals, alcohols, and organomineral compounds, eg, Grignard reagents (10,45). In autoxidations involving hydrazones, double-bond migration occurs with the formation of hydroperoxy—azo compounds via free-radical chain processes (10,59) (eq. 20). 

Enol ethers (15) and mixed acetals (16) are readily obtained from secondary but not from tertiary alcohols, whereas tetrahydropyranyl ethers can be formed even from tertiary alcohols. This is a result of the greater steric requirements of the reagents (17) and (18) as compared to (19). 

The enol ethers (56) and (57) are prepared from the corresponding ketals (54) and (55) in both 5a- and 5j5-series by pyrolytic or catalytic elimination of one molecule of alcohol. 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

The first asymmetric Mn(salen)-catalyzed epoxidation of silyl enol ethers was carried out by Reddy and Thornton in 1992. Results from the epoxidation of various silyl enol ethers gave the corresponding keto-alcohols in up to 62% ee Subsequently, Adam and Katsuki " independently optimized the protocol for these substrates yielding products in excellent enantioselectivity. 

This valuable method utilizes the O-TMS enol ethers derived from either pentane-2,4-dione or methyl acetoacetate, the former being the more reactive. Even t-alcohols are rapidly and quantitatively silylated in DMF at room temperature. A similar technique can be used to introduce the TBDMS group, although here ptsa catalysis is required (4). 

For those substrates more susceptible to nucleophilic attack (e.g., polyhalo alkenes and alkenes of the type C=C—Z), it is better to carry out the reaction in basic solution, where the attacking species is RO . The reactions with C=C—Z are of the Michael type, and OR goes to the side away from the Z. Since triple bonds are more susceptible to nucleophilic attack than double bonds, it might be expected that bases would catalyze addition to triple bonds particularly well. This is the case, and enol ethers and acetals can be produced by this reaction. Because enol ethers are more susceptible than triple bonds to electrophilic attack, the addition of alcohols to enol ethers can also be catalyzed by acids. " One utilization of this reaction involves the compound dihydropyran... 

Selenski investigated the use of chiral enol ether auxiliaries in order to adapt method F-H for enantioselective syntheses. After surveying a variety of substituted and unsubstituted enol ethers derived from a vast assortment of readily available chiral alcohols, she chose to employ enol ethers derived from trans-1,2-phenylcyclohexanol such as 73 and 74 (Fig. 4.37). These derivatives were found to undergo highly diastereoselective cycloadditions resulting in the formation of 75 and 76 in respective... 

Alkenes are scavengers that are able to differentiate between carbenes (cycloaddition) and carbocations (electrophilic addition). The reactions of phenyl-carbene (117) with equimolar mixtures of methanol and alkenes afforded phenylcyclopropanes (120) and benzyl methyl ether (121) as the major products (Scheme 24).51 Electrophilic addition of the benzyl cation (118) to alkenes, leading to 122 and 123 by way of 119, was a minor route (ca. 6%). Isobutene and enol ethers gave similar results. The overall contribution of 118 must be more than 6% as (part of) the ether 121 also originates from 118. Alcohols and enol ethers react with diarylcarbenium ions at about the same rates (ca. 109 M-1 s-1), somewhat faster than alkenes (ca. 108 M-1 s-1).52 By extrapolation, diffusion-controlled rates and indiscriminate reactions are expected for the free (solvated) benzyl cation (118). In support of this notion, the product distributions in Scheme 24 only respond slightly to the nature of the n bond (alkene vs. enol ether). The formation of free benzyl cations from phenylcarbene and methanol is thus estimated to be in the range of 10-15%. However, the major route to the benzyl ether 121, whether by ion-pair collapse or by way of an ylide, cannot be identified. 

A limitation to the use of the Tebbe reagent 93 was observed during the attempted conversion of substrates 139 and 142 to the tricyclic systems 141 and 144 respectively (Scheme 21). The major products from these reactions were olefinic alcohols 140 and 143. These products presumably resulted from sequential hydrolysis and olefination of the initially formed cyclic enol ethers. The problem associated with these sensitive substrates was overcome through use of the less Lewis-acidic Petasis reagent 110, which provided access to the desired products 141 and 144 [34a]. 

The isomeric propargylic stannylated aldehyde intermediate, on the other hand, could be prepared from the alcohol precursor without competing cyclization to an seven-membered enol ether product (Eq. 9.105). Treatment of this stannane with SnCl4 afforded the cis-disubstituted tetrahydrofuran stereoselectively. Presumably, this reaction proceeds through an allenyl trichlorostannane intermediate. 

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