Methoxymethyl cleavage

The cleavage proceeds by initial reduction of the nitro groups followed by acid-catalyzed cleavage. The DNB group can be cleaved in the presence of allyl, benzyl, tetrahydropyranyl, methoxy ethoxy methyl, methoxymethyl, silyl, trityl, and ketal protective groups. 

R SiBr, trace MeOH. Methoxymethyl ethers are stable to these cleavage conditions. Methoxymethyl esters are unstable to silica gel chromatography, but are stable to mild acid (0.01 N HCl, EtOAc, MeOH, 25°, 16 h)." ... 

The relationship, between magnitudes of these sensitivity parameters and the reactivity of the system concerned, was explored quantitatively for three sets of acetal structures, and a further linear relationship was found (Kirby and Jones, 1986). Figure 25 shows a plot of the sensitivity parameter against relative reactivity for series of compounds, tetrahydropyranyl-, methoxymethyl- and a-glucosyl-OX, known to react with C-OX cleavage at very different rates (relative rates of hydrolysis approximately 1, 103 5 and 106 5, respectively). The correlation is good for both the intercepts (i.e. the... 

SAMP/RAMP-Hydrazones are cleaved oxidatively by ozonolysis in dichloromethane at — 78 °C3. This method proceeds within 15 to 30 minutes/10 mmol in quantitative yield without racemization. The endpoint of the cleavage reaction is indicated by the green color of the yellow nitrosamine with blue ozone. Besides the desired carbonyl compound, one quivalent of (S)- or (/J)-2-methoxymethyl-l-nitrosopyrrolidine is formed. 

Hydrazones prepared from (S)- l-amino-2-(methoxymethyl)pyrrolidine (242) and acyclic ketones have been shown to undergo deprotonation and alkylation with almost complete asymmetric induction at the a-center (79AG(E)397). The ant alarm pheromone, (+)-(5)-4-methyl-3-heptanone (245), was prepared from the metallated hydrazone of diethyl ketone (243) by alkylation with n-propyl iodide and subsequent cleavage of the crude product via its JV-methyl iodide with acid (Scheme 52). The optical purity of the product was >99%. 

Cleavage of terminal tyrosyl and tryptophanyl peptides. L-Tyrosyl-L-alanine (1) and related dipeptides are cleaved by 01 1(0Ac)2 in CH3OH containing KOH to 4-(methoxymethyl)phenol (2) and an amino acid. Under the same conditions, L-tyrosine yields (4-hydroxyphenyl)acetonitrile, HOC6H4CH2CN. The phenolic hydroxyl group and the free amino group are essential for this cleavage.1... 

Macrocytic lactonization.2 Lactonization of 1 was effected most efficiently with this carbodiimide. Subsequent cleavage of the methoxymethyl ether (Nal in acetone) results in the antibiotic milbemycin / 3 (2) in 85% overall yield. 

Tetrahydropyranyl (THP) ethers, another species known to be unstable to acid, have similarly been reported to be cleaved by solutions of iodine in methanol.209 At room temperature, cleavage of the THP ethers was complete in 1.5 to 8 h. As with the previous example using iodine in methanol at lower than reflux temperature, TBDMS ethers were stable to these conditions. The ability to tune the reactivity of the iodine in methanol system by simply controlling the temperature is of value in selective deprotection. This is even more useful when fluorine, known to remove only silyl ethers,105 is exploited. Given that methoxymethyl ethers, essentially acetals, are known to be cleaved under acidic conditions, it seems likely they too should be subject to removal by solutions of iodine in methanol. Sundry examples of deprotections using iodine in methanol are presented in Table IV. 

An efficient asymmetric synthesis of the 3-substituted /3-sultams 163 has been reported. The key step of the synthesis is the Lewis acid-catalyzed aza-Michael addition of the enantiopure hydrazines (A)-l-amino-2-methoxy-methylpyrrolidine (SAMP) or CR,l ,l )-2-amino-3-methoxymethyl-2-azabicyclo[3.3.0]octane (RAMBO) to the alke-nylsulfonyl sulfonates 176. /3-Hydrazino sulfonates were obtained in good yield and excellent enantioselectivity. Cleavage of the sulfonates followed by chlorination resulted in the corresponding sulfonyl chlorides 177. The (A)-3-substituted /3-sultams 163 have been obtained in moderate to good yields and high enantioselectivity over two steps, an acidic N-deprotection followed by in situ cyclization promoted by triethylamine (Scheme 55) <2002TL5109, 2003S1856>. 

The next step was the introduction of the methylene acetal residue in 6 and 7 (Scheme 5). The initial plan was to effect this transformation in a single step, by exposure of the methoxymethyl derivatives 6 and 7 to dimethylboron bromide, following the conditions developed by Roush and co-workers (38). However, this reaction was not successful for either substrate, presumably due to competing cleavage of the acetonide residue. More promising results were obtained with triol 29 (obtainable from controlled hydrolysis of 7). Thus,... 

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. 

The boron reagent 1 is recommended also for cleavage of mono MEM or methoxymethyl ethers of 1,2- or 1,3-diols, which are cleaved by acids mainly to cyclic diol foimals. 

Cleavage of MOM ethers. Methoxymethyl ethers are cleaved by this reagent at 0° in 80-97% yield. Acetals and THP, trityl, and r-butyldimethylsilyl ethers also are cleaved, but less readily.-... 

Cleavage of methoxyethoxymethyl ethers. The reagent selectively cleaves MEM ethers in the presence of benzyl, silyl, allyl, and methyl ethers as well as aeetals, acetates, and benzoates. However, methoxymethyl ethers and aeetonides are cleaved at about the same rate as MEM ethers. 

Cleavage of ethers1 and acetals.2 This reagent cleaves cyclic and acyclic acetals and ketals, including p-methoxyethoxymethyl (MEM), methoxymethyl (MOM), and... 

---