Acetals 2-methoxypropene

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 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]. 

A solution of sucrose (34.2 g, 0.1 mol) in dry DMF (400 mL) containing molecular sieve pellets (Vis in., type 3 A) was stirred with 2-methoxypropene (12.1 mL, 0.13 mol) in the presence of dry p-toluenesulfonic add (25 mg) for 40 min at 70°C, cooled to room temperature, and made neutral with anhydrous sodium carbonate. The inorganic residue wss filtered off and the filtrate evaporated to a syrup. Elution of the syrup from a column of silica gel with 1 1 ethyl acetate/acetone afforded the diacetal 2, l- 4,6-di-0-isopropylidene-sncn>8e 35 as a syrup 3 g (7%) [a]D +25.5° (c 1, methanol). Further elution gave the major product 4,6-O-isopropylidene-sucrose 34 yield 23 g (60%) white powder [a]D +45.4° (c 1.0, methanol).. 

The oldest known method for producing isopropylidene acetals is treatment of a diol with anhydrous acetone under acid catalysis. However, in order to trap the resulting water it is also necessary to include molecular sieves or copper sulfute 2-Methoxypropene (19) is roughly twice as expensive as acetal 18. but as an enol ether it is also more reactive. In especially problematic cases one can in addition resort to 2-trimethylsilyIoxypropene (IPOTMS = isopropenyl-oxytrimethylsilane) (20), but lor this situation it is inappropriate on the basis of cost. 

Carreira et al. used a chiral BlNOL-derived Schiff base-titanium complex as the catalyst for the aldol reactions of acetate-derived ketene silyl acetals (Scheme 8C.29) [64a]. The catalyst was prepared in toluene in the presence of salicylic acid, which was reported to be crucial to attain a high enantioselectivity. A similar Schiff base-titanium complex is also applicable to the carbonyl-ene type reaction with 2-methoxypropene [64b], Although the reaction, when con-... 

Synthesis of acetonides can also be performed using 2-methoxypropene instead of 2,2-dimethoxypropane <20050L5011> however, 4,5-dihydro-l,3-dioxepins, such as 216 (Scheme 61), can only be obtained by direct acetalization or transacetalization with special substrates. 

It is not always easy to ascertain if the addition reaction proceeds via the triplet excited state of the arene. Benzene and its simple derivatives such as anisole and benzonitrile have high triplet energies (benzene, 84 kcal/mol 1 anisole, 81 kcal/mol" benzonitrile, 77 kcal/mol-1) which makes sensitization impracticable. Results of quenching experiments are sometimes difficult to interpret, as has become evident from the work of Cantrell. He found [109] that the formation of adducts from benzonitrile and 2,3-dimethylbut-2-ene, vinyl acetate, and 2-methoxypropene in solutions 0.5 M in cri-l,3-pentadiene occurs at a rate only approximately one-fourth that in the absence of added quencher. Five years later, the author reported [110] that m-l,3-pentadicnc itself adds slowly to benzonitrile to give ortho adducts. When a correction was made for the reaction of benzonitrile with the quencher, it became apparent that little, if any, triplet quenching had occurred. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

Ciufolini et al. developed carbonyl-ene reactions catalyzed by the 1 1 complex of Yb(fod)3 and acetic acid [19]. 2-Methoxypropene reacted with a variety of aldehydes under the conditions used, providing the protected alcohols in good yields (Eq. 9). Addition of acetic acid was essential —the reaction did not proceed with Yb(fod)3 alone. Addition of silica gel to the reaction mixture was found to enhance the rate of the reaction and to make the reaction clean, although the use of silica gel was not mandatory. Double activation of the aldehydes as a result of coordination to the Yb Lewis acid and hydrogen-bonding with the acidic hydrogen of the acetic acid was proposed for the reaction (Fig. 2). 

The strong tendency for acetalization of cA-l,2-diols is exemplified by the reaction of glucopyranose A, which on treatment with acetone in the presence of a catalytic amount of H2SO4 furnishes the l,2 5,6-di-D-isopropylidene-a-D-glucofuranose B (thermodynamic product). However, kinetic acetalization with 2-methoxypropene in DMF in the presence of TsOH as a catalyst at 0 °C occurs without rearrangement to give the 4,6-isopropylidene glucopyranose... 

---