Lithium-ammonia reduction epoxides

The difficultly accessible trans-syn-trans arrangement of the a-b-c ring system present in steroidal antibiotics has now been synthesized. The known enedione (39) was converted into a 6 1 mixture of the desired compound (40) and its isomer (41) by ketalization of the saturated carbonyl, followed by lithium-ammonia reduction and enolate trapping with methyl iodide. After separation, (40) was converted into the tricyclic enedione (42) by standard procedures. The transfused AB-system was then obtained by ketalization, peracid treatment, and boron trifluoride rearrangement of the resulting epoxide to the keto-diketal (43). Removal of the 6-keto-group was performed under mild conditions by a new... 

Zirconium(IV) isopropoxide, 352 Reductive alkylation of aromatic rings Birch reduction, 32 (S)-Prolinol, 261 of carbonyl groups Trityl perchlorate, 339 of other substrates Lithium-Ammonia, 158 Reductive cleavage (see also Reduction of epoxides)... 

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). 

To arrive at racemic coriolin, Danishef sky and coworkers chose to add an acetonyl fragment to a bicyclic enedione by Diels-Alder chemistry (Scheme LXXIII) Treatment of the resulting adduct 695 sequentially with a series of conventional reagents produced the key intermediate 696. Suitable aldolization deUvered 697, the functionality in which was adjusted by deconjugation and reduction. Fiuther reduction of dPSiwith lithium in liquid ammonia and methanol followed by epoxidation afforded 699. Selective oxidation of the more accessible hydroxyl group and phenyl-sulfenylation gave 700 which experiences smooth elimination to 701 after conversion to the sulfoxide. As before, epoxidation completed the sequence. 

I) by oxidation with m-chloropcrbcnzoic acid, with 2 equivalents of lithium in liquid ammonia gives the alcohol (3) in 90% yield. In the same way, the epoxide (4) is converted into (5) in 95 % yield. In both cases (2) and (4) the cyclopropyl bond common to ihe two phenyl substiluents is ruptured with marked kinetic preference to give a radical anion, which is attacked by the proximate C-0 bond to form a new cyclopropane ring. The cyclopropane ring of (3) and of (5) is presumably protected from further reduction by dectrostatic factors. 

One of die most popular reactions in organic chemistry is dissolving metal reductions [1-3], Two systems are frequently used - sodium dissolved in ammonia with alcohol and lithium dissolved in alkylamines [4]. Although calcium is seldom used, it has been successfully applied to the reduction of a variety of compounds and functional groups [5], including aromatic hydrocarbons, carbon-carbon double and triple bonds, benzyl ethers, allyl ethers, epoxides, esters, aliphatic nitriles, dithianes, als well as thiophenyl and sulfonyl groups. 

Synthesis of racemic (178) is shown in Scheme 37. Ketoester (177), synthesized from naphthalene-1,6-diol via 5-methoxy-2-tetralone, was converted into compound (180) by successive methylation at C-4, acetali-zation at C-3, reduction of the ester group to hydroxymethyl group, epoxidation of the C-5, C-6 double bond, and ring opening of the epoxide. Birch reduction of diol (180) with 18 equivalents of lithium in liquid ammonia followed by acid hydrolysis and subsequent methyl acetalization... 

Another route to the [4,1,0,0 ] system (824) is also reported. Reduction of the epoxide (834) with lithium in ammonia gives 90% of (835) by reductive cleavage of the diphenylcyclopropane and rear attack by a carbanion so formed on the epoxide ring. The homologue (836) behaves in the same way. ... 

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