Cleavage rules

Figure 8.2 The set of 11 default bond cleavage rules in RECAP.

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). 

Double bonds favor cleavage beta to the carbon (but see rule 6). 

Salicylonitrile is believed to arise by direct cleavage with subsequent hydrogen transfer, while the benzoxazoles were produced by an isocyanide intermediate (73JA919, 74HCA376). Photolysis in D2O tends to confirm this possibility and rule out an azirine intermediate (39), due to deuterium corporation into the molecule (Scheme 10) (74HCA376). 

The structure of 82 was established by alkaline ring cleavage to benzilic acid amide and by hydrogenolysis to (C6H5)2CH—CONH— COCfiHs. These reactions also served to eliminate 83 as the structure of the 169° compound. The other possible isomeric structure, (C6H5)2C(CN)0C0C6H5, which could have formed after 0-acylation, was ruled out by its independent synthesis from bromodiphenyl-acetonitrile and silver benzoate. 

N-Nilrosoamines are reduced easily lo ihe hydrazine and, if continued, lo the amine (62). Early workers ruled out cleavage of dimeihylhydrazine as the source of dimethylamine in hydrogenation of N-nitrosodimethylamine since liule ammonia was found the letramethylietrazene was implicated in the hydrogenolysis (fSI). Palladium-on-carbon under mild conditions is used for industrial production of dialkyl hydrazines from N-nitrosoamines. 

The above results do not rule out the possibility that nucleophilic attack on silicon assists the cleavage, a transition state such as (XL), below being involved,... 

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