Ethers primary cleavage

As for (i-0-4 ethereal bond cleavage, reaction of the primary cation-radical with solvent water under the same conditions of bio-oxidation was shown to form an arylglycerol and the corresponding phenoxy radical (Kirk et al. 1986, Fabbri et al. 2005) (Scheme 8.22). Since the p-0-4 ethereal bond is the most abundant type of interunit linkage in the lignin polymer, this ethereal bond cleavage represents an important depolymerization reaction. 

Aromatic Ethers The molecular ion peak of aromatic ethers is prominent. Primary cleavage occurs at the bond j8 to the ring, and the first-formed ion can decompose further. Thus anisole, MW 108, gives ions of m/z 93 and 65. 

Copper chromite (CuCr204) has historically been widely used as a hydrogenation catalyst. Generally because of its low catalytic activity its chemoselectivity is useful, although it does require high temperature and autoclave pressure conditions. It is effective for cleavage of benzylic alcohols, primary and secondary benzylic esters and ethers. Efficient cleavage of benzylamines has also been utilized (equation 29). Other copper salts and copper alloys have found infrequent use. 

The mechanism of add-catalyzed deavage of dialkyl ethers depends on the nature of the carbons bonded to oxygen. If both carbons are primary, cleavage involves an reaction in which a halide ion is the nudeophile. Otherwise, deavage is by an S l reaction. 

Primary TBDMS ethers can be cleaved selectively in the presence of THP ethers and ketals using ceric ammonium nitrate in methanol. Both phenolic and aliphatic TBDMS ethers undergo cleavage when exposed to catalytic amounts of PdCl2(MeCN)2 in the latter case, and with longer exposure, this also results in oxidation to the corresponding aldehyde or ketone, if the alcohol was primary or secondary, respectively. This cleavage and oxidation can be performed selectively in the presence of TIPS, TBDPS and benzyl ethers (equation 15). 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Oxidative Reactions. The majority of pesticides, or pesticide products, are susceptible to some form of attack by oxidative enzymes. For more persistent pesticides, oxidation is frequently the primary mode of metaboHsm, although there are important exceptions, eg, DDT. For less persistent pesticides, oxidation may play a relatively minor role, or be the first reaction ia a metaboHc pathway. Oxidation generally results ia degradation of the parent molecule. However, attack by certain oxidative enzymes (phenol oxidases) can result ia the condensation or polymerization of the parent molecules this phenomenon is referred to as oxidative coupling (16). Examples of some important oxidative reactions are ether cleavage, alkyl-hydroxylation, aryl-hydroxylation, AJ-dealkylation, and sulfoxidation. 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary versus secondary alcohols can be achieved (ratios = 4.3-4.6 1). They are cleaved electrolytically ( — 1.4 V, 0.5 M HBF4, MeOH, 70% yield). Since picolyl chlorides are unstable as the free base, they must be generated from the hydrochloride prior to use. These derivatives are relatively stable to acid (CF3CO2H, HF/anisole). Cleavage can also be effected by hydrogenolysis in acetic acid. ... 

Bu2BOTf, BH3-THF, CH2CI2, 0°, 70-91% yield. In a variety of pyrano-sides, cleavage occurs primarily to give the primary alcohol, with the secondary alcohol protected as the benzyl ether." ... 

Acidic ether cleavages are typical nucleophilic substitution reactions, either SN1 or Sn2 depending on the structure of the substrate. Ethers with only primary and secondary alkyl groups react by an S 2 mechanism, in which or Br attacks the protonated ether at the less hindered site. This usually results in a selective cleavage into a single alcohol and a single alkyl halide. For example, ethyl isopropyl ether yields exclusively isopropyl alcohol and iodoethane on cleavage by HI because nucleophilic attack by iodide ion occurs at the less hindered primary site rather than at the more hindered secondary site. 

From intermediate 12, the path to key intermediate 7 is straightforward. Reductive removal of the benzyloxymethyl protecting group in 12 with lithium metal in liquid ammonia provides diol 27 in an overall yield of 70% from 14. Simultaneous protection of the vicinal hydroxyl groups in 27 in the form of a cyclopentanone ketal is accompanied by cleavage of the tert-butyldimethylsilyl ether. Treatment of the resultant primary alcohol with /V-bromosuccini-mide (NBS) arid triphenylphopshine accomplishes the formation of bromide 7, the central fragment of monensin, in 71 % yield from 27. 

With the iodine atom in its proper place, provisions for construction of the C9-C10 bond by an aldol reaction could be made (see Scheme 44). To this end, oxidative cleavage of the para-methoxy-benzyl ether in 181 with 2,3-dichloro-5,6-dicyano-l,4-benzoqui-none (DDQ) in CH2CI2-H2O furnishes a primary alcohol that can... 

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