Trimethyl-orthoacetate

The trivial name acetoxy is retained for the CH3—CO—O— group. Compounds of the type R C(0R )3 are named as R esters of the hypothetical ortho acids. For example, CH3C(OCH3)3 is trimethyl orthoacetate. 

Addition reactions such as A-alkylation do not occur readily, and trimethylsilylmethylation of 3,4-diphenyl-l,2,5-thiadiazole 8 with trimethylsilylmethyl trifluoromethanesulfonate at 80°C occurred at N-2 < 1999J(P1) 1709>. The electron-rich 3-hydroxy-l,2,5-thiadiazole can be preferentially methylated on N-2 using trimethyl orthoacetate in toluene to afford the 2-methyl-l,2,5-thiadiazol-3-one in 69% yield <2002EJ01763>, although a mixture of 3-hydroxythiadiazole and neat trimethyl orthoacetate showed a 20 80 ratio of N- versus 0-alkylation products by H NMR. Treatment of 3-hydroxy-l,2,5-thiadiazole with /-butyl acetate under acid catalysis (Amberlyst 15) gave almost exclusively the A-alkylated compound <2002BMC2259>. 

Hydroxythiadiazole and neat trimethyl orthoacetate showed a 20 80 ratio of N- versus O-alkylation products by H NMR <2002EJ01763>. The acidic hydroxyl group of thiadiazole 130 can be selectively protected as the benzyl ether 113 (Equation 22) <2004TL5441>. Nonhydrogenative debenzylation of the bisbenzyl thiadiazole 116 was achieved with boron tribromide to afford the bis-l,2,5-thiadiazole 131 (Equation 23) <2004TL5441>. 

Prolonged reaction of the triols 25 with trimethyl orthoacetate and a weakly acidic catalyst affords a mixture of the 5- and 6-membered oxacycles from which the tetrahydropyran is obtained on equilibration (Scheme 13). By selection of the reaction conditions, it is possible to obtain either ring system exclusively <00CC1781>. 

Alkoxyallenes turned out to be excellent starting materials also for the synthesis of highly functionalized 1,3-dienes, two examples being depicted in Schemes 8.61 and 8.62. As described by Kantlehner et al., 1,3-dienes such as 238 were obtained from methoxyallene derivative 50 by condensation with CH-acidic compounds 237 [135]. Hoppe and co-workers explored the stereochemical course of the allene Claisen rearrangement under Johnson s conditions, e.g. the reaction of 239 with trimethyl orthoacetate, which furnished intermediate 240 followed by rearrangement to the isomeric dienes 241a,b [136],... 

D. (3S, 4E)-Methyl 3-(dimethylphenylsilyl)-4-hexenoate (4a). A stirred solution of 6.0 g (29.11 mmol) of alcohol 3a and 60 mL of dry toluene in a 200-mL flask equipped with a reflux condenser is treated with 15 mL (116.89 mmol) of trimethyl orthoacetate and 0.15 mL (2.01 mmol, 0.07 equiv) of propionic acid (Note 15). The reaction mixture is heated under reflux for 48 hr and then allowed to cool to room temperature. Solvents and volatile material are removed under reduced pressure to leave the crude (E)-crotylsilane 4a as a yellow oil. The crude residue is chromatographed on silica gel (gradient elution 5% EtOAc/hexanes). The eluant (Note 6) affords 6.58 g (25.1 mmol, 86%) of pure 4a as a faint yellow, viscous oil (Notes 6, 16 and 17). 

Toluene is freshly distilled from calcium hydride. Trimethyl orthoacetate, 99%, and propionic acid, 99%, are purchased from Aldrich Chemical Company, Inc., and used as supplied. 

Trimethyl orthoacetate Orthoacetic acid, trimethyl ester (8) Ethane, 1,1,1-trimethoxy-(9) (1445-45-0)... 

In contrast to Mori s synthesis, Pawar and Chattapadhyay used enzymatically controlled enantiomeric separation as the final step [300]. Butanone H was converted into 3-methylpent-l-en-3-ol I. Reaction with trimethyl orthoacetate and subsequent Claisen-orthoester rearrangement yielded ethyl (E)-5-methyl-hept-4-enoate K. Transformation of K into the aldehyde L, followed by reaction with ethylmagnesium bromide furnished racemic ( )-7-methylnon-6-ene-3-ol M. Its enzyme-catalysed enantioselective transesterification using vinylacetate and lipase from Penicillium or Pseudomonas directly afforded 157, while its enantiomer was obtained from the separated alcohol by standard acetylation. 

Allylic alcohol 124 (R1 = H 113 mg, 0.34 mmol), trimethyl orthoacetate (0.21 mL, 1.7 mmol), and benzoic acid (4 mg, 0.033 mmol) were dissolved in o-xylene (5 mL) and refluxed for 4 h, when a small amount of starting material was still present by TLC. Additional trimethyl orthoacetate (0.21 mL, 1.6 mmol) and benzoic acid (4 mg, 0.033 mmol) were added and the solvents removed. The residue was flash chromatographed (silica gel, hexanes/EtOAc 5 1) to provide the fra/w-alkene 125 yield 81 mg (55%). 

Conducting the first two steps as a one-pit reaction10 was first suggested by Sharp less. Transacetalization of trimethyl orthoacetate with 10 under weakly acidic catalysis leads to the 2-methoxy-l,3-dioxolane 34. Addition of TMSC1 or acetyl chloride generates the 1,3-dioxolanylium cation 35, which is opened nucleophilically and regioselectively at the sterically least hindered position to chloro-acetate 36... 

Diols such as 87 are converted in excellent yields [89] into acetoxy chlorides (88) by treatment with trimethyl orthoacetate and trimethylsilyl chloride [90] or into acetoxybromides (89) with trimethyl orthoacetate and acetyl bromide [91]. These reactions proceed through nucleophilic attack on an intermediate l,3-dioxolan-2-ylium cation [91] with inversion of configuration. In the presence of an aryl substituent as in 87, displacement occurs exclusively at the benzylic position. With aliphatic diols such as 90, the halide is introduced mainly at the less hindered position and acetoxybromides 91 and 92 are formed in a ratio of 7 1. Treatment of the acetoxy halides 88 or 89 under mildly alkaline conditions affords epox.de 93 in 84-87% yield while the mixture of 91 and 92 is converted to epoxide 94 in 94% yield. Because both... 

Dansette and Jerina25 found that cis- 1,2-glycols (34) on treatment with trimethyl orthoacetate in refluxing benzene containing a trace of benzoic acid are converted to an enantiomeric mixture of 2-methyl-2-methoxydioxolanes (orthoesters) (35 and 36). On reaction of this mixture with trimethylsilyl chloride, substitution with inversion takes place, and trans-chlorohydrin acetate (37) is formed. The chlorohydrin acetate is cyclized to an arene oxide on treatment with sodium methoxide. 

The acid-catalysed rearrangement of 2,4,5-triols leads to the thermodynamic product, a tetrahydrofuran. However, cyclisation using trimethyl orthoacetate and pyridinium toluene-p-sulfonate gives a mixture of the THF and a tetrahydropyran, in which the former predominates, by attack of the primary hydroxy group at different ends of the episulfonium ion intermediate. This route nevertheless provides a useful route to THPs through equilibration of this reaction mixture <02JCS(P1)2646,02JCS(P1)2652>. 

A considerable amount of effort has already been devoted to producing dimethyl carbonate (DMC) from methanol and CO2, and some of the reactions have been catalyzed by organotin alkoxides. However, the catalytic activities so far obtained have been very low due to the decomposition of the catalysts by water generated during the reaction. The supercritical C02 reaction with trimethyl orthoacetate leads to the desired reaction and gives DMC and methyl acetate. Although di- -butyltin dimethoxide is less effective, the addition of tetrabutylphosphonium iodide substantially enhances the catalytic activity of the system (Equation (96)).261 262... 

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