Ethers cleavage with acetic anhydride

Ether cleavage can also be effected by reaction with acetic anhydride and Lewis acids such as BF3, FeCl3, and MgBr2.97 Mechanistic investigations point to acylium ions generated from the anhydride and Lewis acid as the reactive electrophile. 

Although the conditions used to cleave the ether linkage are vigorous, we decided to attempt this reaction on the a -alkoxy N-nitrosamines. The cleavage of ethers with acetic anhydride in the presence of Lewis acids is well-known in the literature (12,13,14). Reaction of a -methoxy dimethylnitrosamine IV with Ac20 in the presence of BF3 etherate at 60° resulted in the cleavage not only of the C-0 bond but also the N-C bond (15,16). ... 

However, these synthetic procedures were useful only in the preparation of primary a-acetoxymethyl alkylnitrosamines and a-chloromethyl alkylnitrosamines. The cleavage of secondary ethers, such as XIII with acetic anhydride or acetyl chloride was so vigorous that no characterizable substances could be isolated. In view of this problem, we looked for another synthetic route which would allow the isolation of secondary derivatives. The first experiment tried, namely that of nitrosyl chloride with N-methylene t-butylamine at -30° was successful. The addition of NOCl at this temperature... 

Cleavage of Ethers with Acetic Anhydride Acyloxy-de-alkoxylation... 

Figure 4-5. Reaction mechanism for the derivatization followed by reductive cleavage based on Lu and Ralph (1997). Reaction of the lignin with acetylbromide (AcBr) results in the acetylation of the y-carbon, while the a-carbon is brominated. Zinc (Zn) catalyzes the cleavage of the ether bond between the P-carbon of one residue and the 0-4 position of the adjacent residue. The resulting monomer is acetylated with acetic anhydride (Ac20) and pyridine (Py). R can be a proton or an aryl group. In H-residues R3 and R5 are protons, in G-residues R3 is a methoxyl group and R5 is a proton, whereas in S-residues both R3 and R5 are methoxyl groups. The wavy bonds indicate that both the S- and R- (4.26, 4.27) or E- and Z-stereo-isomers (4.28, 4.29) are present.

Regioselective debenzylation can be achieved by treatment with Lewis acids such as ferric chloride and S11CI4 or under acetolysis conditions with acetic anhydride and sulfuric acid, and several examples are depicted in Scheme 2.3.9 Acetolysis results in cleavage of the most acid-sensitive benzyl group. In general, primary benzyl ethers can be selectively acetolysed in the presence of secondary benzyl ethers. The regioselectivity of the reaction can be explained as follows sulfuric acid protonates acetic anhydride followed by the formation of an acetyl ion and acetic acid. The acetyl ion reacts with the sterically most accessible oxygen which is at... 

Cycloaddition of nitriles with dipropargyl ethers. A new synthesis of pyridoxine (4, vitamin BJ is based on the (2 + 2 + 2 cyclo.iddition of acetonitrile with dipropargyl ethers catalyzed by Cp,Co or Cp(CO),Co to torn the pyridine derivative I. Subsequent steps involve rearrangement of the N-oxide of 1 to the 3-hydroxypyridine 2 with acetic anhydride. The final step involves the known cleavage of the dihydrofuranc ring. 

Ether cleavage. Treatment of the keto ether (1,9-oxatricyclo[4.3.3.0]doUecane-3-one) with acetic anhydride and pyridine hydrochloride (reflux 5,5 hr.) yields the diacetatc (2, 4-acctoxy-l-(2-acetoxyethyl)bicyclo[4,3.0]nonadiene-4,6) in 93% yield. 

Reaction of 12 with diazomethane gives an 0-methyl ether (mp 144-145°) and acetylation of 12 in acetic anhydride-pyridine solution for a short time (5 min) gives the 0-acetyl derivative 13 (mp 174-175°). Prolonged reaction of 12 with acetic anhydride-pyridine at room temperature, however, gives the iV-acetyl compound 14 (4). The formation of 14 can be explained by further acetylation of 13 to give the 7-acetoxy compound followed by elimination of acetic acid to give an unsaturated ketone and finally cleavage of the C-9-N bond by the mechanism indicated in 15. 

When the epoxide (presumably the a-form, XXXIV) is reduced with lithium aluminum hydride in ether-benzene and the reaction product reacetylated with acetic anhydride-pyridine, there is formed an 0,0 -diacetyl-W-ethylhydroxydihydroveratramine (XL), which readily loses water in contact with thionyl chloride-pyridine to generate an 0,0 -diacetyl-iV-ethylveratramine (XLI). During this reduction there is also formed a product which on reacetylation proved to be 0,0 -diacetyl-iV-ethyldihydroxydihydroveratramine (XLII). Its structure is uncertain but it appears to be formed by hydrolytic rather than reductive cleavage of the epoxide ring (42). 

Ether Cleavage. Dialkyl ethers can be cleaved with acetic anhydride in the presence of pyridine hydrochloride or anhydrous Iron(III) Chloride. In both cases, acetate products are produced. As shown in eq 43, the tricyclic ether is cleaved by acetic anhydride and pyridine hydrochloride to give the diacetate in 93% yield. 

The elaboration of 113 to (—)-kinamycins C, F, and J, is shown in Scheme 3.19. To access ( )-kinamycin C (3), the silyl ether function of 113 was cleaved with aqueous hydrochloric acid (95 %). Alternatively, treatment of 113 with lithium hydroxide served to liberate the phenol function and saponify the three acetate esters, to provide ( )-kinamycin F (6) in 92 % yield. Finally, acylation of the tertiary hydroxyl of 113 (acetic anhydride, triethylamine) afforded a tetraacetate. Cleavage of the silyl ether then provided ( )-kinamycin J (10) in 80 % over two steps. 

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