2- Methoxypropene

A useful entry into p-keto allenes is provided by the reaction of 2-MP with tertiary propaigylic alcohols. Base-catalyzed rearrangement of the allenes affords conjugated dienones (eq 3). 

Form Supplied in colorless liquid commercially available. Preparative Method prepared in high yield from Succinic Anhydride, 2,2-Dimethoxypropane, benzoic acid, and Pyridine Handling, Storage, and Precautions flammable liquid light-sensitive should be refrigerated. 

Monoprotection of Alcohols. 2-Methoxypropene is used as a protective group for aliphatic, allylic, and propargylic alcohols, masking them as their mixed acetals (eq 1). Deprotection can be accomplished by stirring in MeOH over ion exchange resin, by reaction in methanol with catalytic Acetyf Chloride, by Potassium Carbonate in methanol, or by 20% Acetic Acid. 

A general advantage of this acetal, which undergoes hydrolysis at approximately 10 times the rate of THP, is that it does not confer an additional diastereomeric center to the protected substrate. Access to allyl vinyl ethers for subsequent Claisen rearrangements is illustrated in eq 2. 

Stable allylic peroxyacetals have been prepared by reacting 2-MP with hydroperoxides (eq 4). Organomercury functionality is tolerated in this reaetion. Cyanohydrins, o-hydroxy ketones, and phenols are similarly protected. 

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Under these conditions 2-methoxypropene reacts to form the kinetically controlled 1,3-O-isopropylidene, instead of the thermodynamically more stable 1,2-O-isopropylidene. ... 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

This catalyst is also active toward the simple enol ether 2-methoxypropene.1... 

The hydroxyl group in alcohol 122 is then oxidized. Deprotonation of this ketone with KHMDS (1 eq.), followed by the addition of Davis oxaziridine (see Chapter 4 for a-hydroxylation of ketones)28 (2 eq.) allows the stereo-controlled introduction of the C-10 oxygen from the less hindered enolate face, providing only the (i )-hydroxyketone 123. Subsequent reduction of 123 with excess LAH provides the tetra-ol 124. Treatment of this compound with imidazole and TBSC1 followed by PPTS and 2-methoxypropene provides in one operation the acetonide 125 with 91% yield (Scheme 7-37). 

Oxidative cleavage of the terminal double bond of 49 by ozonolysis to the aldehyde followed by permanganate oxidation to the acid and esterification with diazomethane produced the methyl ester 50. Dieckmann cyclisation of 50, following the procedure developed in Holton s laboratory (LDA, THF, -78 °C, 0.5 h, then HOAc, THF), gave the enol ester 5J in 93% yield (90% conversion). Decarbomethoxylation of 5J. was carried out by temporarily protection of the secondary alcohol (p-TsOH, 2-methoxypropene, 100%), and heating the resulting compound 52 with PhSK in DMF, at 86 °C (3 h) to provide 53a or, after an acidic workup, the hydroxy ketone 53b. 92% yield. 

The addition of gem-disubstituted olefins, CH2=CXY, on polysilane 2 also worked well [23,24], For example, the addition of 2-methoxypropene and methylenecyclohexane afforded the expected adducts with 73% and 77% degrees of substitution, although a higher loss of molecular weight with respect to the hydrosilylation of monosubstituted olefins is observed. Copolymer 21, containing both mono- and disubstituted olefins, was made from 2 in a single reaction by adding 50 mol% vinyl acetic acid and an excess of 2-methoxypro-pene to the THF-polymer solution [24],... 

Although one diastereomer 10 was largely favored, the product was obtained as a mixture of diastereomers, and the previously unreported minor diastereomer 11 was also characterized. The stereochemistry of the products was established by nuclear Overhauser effect (NOE) studies. A plausible mechanism assumes the intermediacy of an acetal, and its reaction with 2-methoxypropene generated from 2,2-dimethoxypropane [20]. In order to test this mechanism, the dimethyl acetal of salicylaldehyde was synthesized and reacted independently with both 2,2-dimethoxypropane and 2-methoxypropene. Indeed, both reactions gave the same products as those from the reaction of salicylaldehyde with 2,2-dimethoxypropane (Scheme 4). The condensation of salicylaldehyde and 2,2-dimethoxypropane was also carried out in CD3CN and reaction progress was followed by H NMR spectroscopy. This experiment also confirmed the formation of the acetal from salicylaldehyde (8 5.52, singlet, C//(OMe)2). 

In 2007, another departure from carbonyl-type activation was marked by Kotke and Schreiner in the organocatalytic tetrahydropyran and 2-methoxypropene protection of alcohols, phenols, and other ROH substrates [118, 145], These derivatives offered a further synthetically useful acid-free contribution to protective group chemistry [146]. The 9-catalyzed tetrahydropyranylation with 3,4-dihydro-2H-pyran (DHP) as reactant and solvent was described to be applicable to a broad spectrum of hydroxy functionalities and furnished the corresponding tetrahydro-pyranyl-substituted ethers, that is, mixed acetals, at mild conditions and with good to excellent yields. Primary and secondary alcohols can be THP-protected to afford 1-8 at room temperature and at loadings ranging from 0.001 to 1.0mol% thiourea... 

The authors successfully applied their protocol to the alternative enol ether 2-methoxypropene (MOP) to prepare the MOP ether 1-8 from a subset of the various alcohol substrates as depicted in Scheme 6.21. This high-yielding (92-97%) MOP protection occurred smoothly at room temperature MOP turned out to be so reactive that the uncatalyzed reaction also proceeded albeit at lower rates [118, 145]. 

The reaction of D-lyxose (7) with 2-methoxypropene gave17 a high yield of 2,3-O-isopropylidene-D-lyxofuranose (9), previously obtained18 in low yield by the conventional procedure [with acetone in the presence of copper(II) sulfate and sulfuric acid]. This reaction probably proceeds through the pyranoid tautomer 8, a kinetic product of the reaction that tautomerizes rapidly to the thermodynamic prod-... 

Finally, all these reactions are catalyzed by p-toluenesulfonic acid, or camphor-sulfonic acid, or pyridinium salts. Use of pyridinium p-tohienesulfonate is now well established as a mild catalyst We have already noted the recent use of DDQ which has recently proved to be effective with 2-methoxypropene [30]. 

The second example concerns the study of acetonation of o-mannose (see Scheme 8) and allows a clear distinction between the use of 2,2-dimethoxypropane and 2-methoxy-propene. Thus, whereas D-matmose gives 2,3 5,6-di-0-isopropylidene-D-mannofuranose 5 by reaction of the free sugar with acetone [5,6] as well as with 2,2-dimethoxypropane [96], the major compound (more than 85%) obtained with 2-methoxypropene is 4,6-0-isopropylidene-D-mannopyranose 6 [52]. Once again, a confirmation of the better stability of furanoid acetals in this series is given by the selective hydrolysis of the 2,3 4,6-di-O-isopropylidene-D-mannopyranose 7 (by-product of the preceding reaction or quantitatively obtained by action of 2-methoxypropene on acetal 6), witch gives the furanoid monoacetal 8. Actually, the pyranoid monoacetal 9 can be easily prepared as soon as the anomeric hydroxyl group is protected by acetylation [52]. 

The acetonation under kinetically controlled conditions is also useful for the protection of vicinal rra/u-diols, which are quite reluctant to cyclization into five-membered rings. Although use of 2-methoxypropene has been successful in this objective [61,66], one should recommend the recently discovered uses of reagents that minimized the ring strain by obtaining six-membered rings from vicinal mmr-dials, which are protected (Scheme 10) as 1,4-dioxanes (dispiroacetals, rranr-decalinic system) stabilized by an anomeric effect... 

A solution of the dry D-glucose diethyl dithioacetal (10.725 g 37.5 mmol) 2-methoxypropene (3.245 g 45 mmol) in anhydrous DMF (130 mL) and p-toluenesulfomc acid (375 mg) was kept for 68 h at 0°C. The homogeneous mixture was kept with exclusion moisture until TLC indicated that all the starting material had reacted, and it was then poured into a solution of sodium hydrogenocarbonate (2% w/v, 60 mL). This mixture was extracted with ether (4 x 30 mL). The combined ether extracts woe washed with water (2 x 30 mL), dried (magnesium sulfate), and evaporated, giving yellowish crystals (8.275 g, 68%) that were recrystallized twice from dichlorometbane petroleum ether to give colorless crystals of 14 yield 5.735 g (47%), mp 73J-74.5°C, [a]D-ll° (c 2.027, methanol). 

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