Reductive cleavage cyclopropanes

The intramolecular cyclopropanation of appropriate y,(5-unsaturated a-diazoketones following a stereoselective catalytic reduction of the cyclopropyl ketone group provides a useful approach in diterpenoid synthesis. Some examples of the use of the cyclopropanation-reductive cleavage approach in synthesis are shown in equations 67 and 68l0f103. 

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). 

Direct reductive cleavage by catalytic hydrogenolysis of a cyclopropane C-C-bond is only possible in exceptional cases, where the three membered ring is further activated by a phenyl or a vinyl group. With unpoisoned catalyst a subsequent reductive desil-oxylation occurs to afford esters like 124 (Eq. 48), whereas addition of small amounts of triethylamine allows isolation of the desired siloxy compounds (e.g. 125, Eq. 49). Interestingly, both reactions demonstrate that the cleavage of the cyclopropane bond proceeds non-stereoselectively with inversion and retention at C-l and C-2, respectively 79). 

Cyclic p-kcio esters and )9-diketones (596) smoothly effect ring-opening of 1,1-bis(benzenesulphonyl)cyclopropane (412) under basic conditions. Reductive cleavage of the resulting sulphones (597) by lithium arylides provides routes to 598 and 599 (equation 210) The bis-benzenesulphonyl compound appears to fulfil the requirements for a propylene 1,3-dipole. The fact that the sulphones can be sequentially removed permits selective introduction of from one to three electrophiles (E) (equation 211). In the case of )5-keto esters, such versatility created a novel three carbon insertion between the ester group and the ketone or a cyclopentane annulation. ... 

Cyclopropyl radicals, anion radicals and anions 2. Reductive cleavage of cyclopropanes... 

Steric and electronic factors in the reductive cleavage of methyl-substituted phenyl cyclopropanes (145) and in spiro[2.4]hepta-4,6-dienes like 146 have been investigated by Staley and Rocchio. ... 

Reductive cleavage of cyclopropane rings. Cyclopropanes can be seductively cleaved by solutions of an alkali metal in liquid ammonia if a carbonyl group (example I),1 a carboxylate group (example II),2 or a phenyl group (example III)3 is attached to the cyclopropyl ring. 

Lithium is the preferred metal for the reductive cleavage of cyclopropane bonds in cyclopropyl ketones. Sodium is less suited for this reaction because it tends to reduce the carbonyl group rather than open the three-membered ring. With sodium the cyclopropane ring in methyl-substituted benzoylcyclopropanes 1 was retained and the benzoyl group reduced to benzyl contrary to lithium which gave rise to the formation of cleavage products. ... 

The reductive cleavage of the proximal cyclopropane bond in bicyclo[3.1.0]heptan-2-ones with samarium(II) iodide involves a one-electron transfer and formation of a radical intermediate which can undergo intramolecular cyclization reactions. ... 

Scheme 7 Ozonization of alcohol (79) followed by treatment of the ozonide with Me2S afforded hydroxy ketones (80), whose acetate derivatives was converted to indenone (83). Hydroxy ketone (84), prepared from (83) was converted to compound (85), whose acetate on oxidation gave diol (87). Its transformation to butenolide (88) was easily carried out. This on oxidation and reduction produced hydroxy phytuberin lactone (89), which was converted to its sulfonyl derivative. Reductive removal of the sulfonate group yielded the cyclopropane derivative (91), which on subjection to reductive cleavage with lithium in liq. NH3 yielded phyberin lactone (92) and deacetyl phytuberin lactone (93)...

Reductive cleavage of the cyclopropane with liq. NH3 in presence of proton donor produced a mixture of phytuberin lactone (92) and deacetyl phytuberin lactone (93). The latter was converted to (92) by reacetylation with acetyl chloride and N.N-diethylaniline. The identification of phytuberin lactone (92) was made by comparison with an authentic specimen.30 The transformation of phytuberin lactone (92) to phytuberin (55) can be accomplished by known procedure.44... 

Reductive cleavage of strained cyclopropanes and cyclobutanes. Dekker et al. have reported reductive cleavage of some strained ring systems by zinc and zinc chloride in protic solvents as shown in the examples. The carbonyl groups are essential for this cleavage. No cleavage is observed in aprotic solvents (e.g., benzene). 

The intramolecular cyclopropanation from (24) to (25), followed by regioselective reductive cleavage of (25) to (26) in the presence of sodium-liquid ammonia has featured in a new synthesis of... 

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