Epoxides with LiAlH

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). 

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

Synthesis of 31 by Method I (107,108) and its conversion to the related anti and syn diol epoxide derivatives (32,33) has been reported (108). The isomeric trans-1,lOb-dihydrodiot 37) and the corresponding anti and syn diol epoxide isomers (38,39) have also been prepared (108) (Figure 19). Synthesis of 37 from 2,3-dihydro-fluoranthene (109) could not be accomplished by Prevost oxidation. An alternative route involving conversion of 2,3-dihydrofluoranthene to the i8-tetrahydrodiol (3-J) with OsO followed by dehydration, silylation, and oxidation with peracid gave the Ot-hydroxyketone 35. The trimethylsilyl ether derivative of the latter underwent stereoselective phenylselenylation to yield 36. Reduction of 3 with LiAlH, followed by oxidative elimination of the selenide function afforded 3J. Epoxidation of 37 with t-BuOOH/VO(acac) and de-silylation gave 38, while epoxidation of the acetate of JJ and deacetylation furnished 39. 

Epoxide reduction with LiAlH (abnormal cis-3,4-epoxy-5-ols 4,5-diols) E. Glotter, Sk Greenfield and D. Lavie, Teimhedron Letters, No. 52 (1967) 5261. 

Direct methods of converting humulene (332) into its 8,9-monoepoxide (337)t and into zerumbone (338) have proved to be very inefficient. Shirahama et al. have now brought about these conversions by indirect means. Thus, for the epoxide (337),169 humulene is first transformed to the acetate (339) by treatment with boron trifluoride etherate in glacial acetic acid followed by mono-epoxidation. Reduction of this acetate with LiAlH, followed by elimination with mesyl chloride in pyridine gives the epoxide (337). In the case of zerumbone (338),170 the readily... 

Finally, treatment with LiAlH, reduces an epoxide to an alcohol. Lithium aluminum hydride is similar to sodium borohydride, NaBH, in that it is a donor of hydride ion, H , which is both a strong base and a good nucleophile. In the reduction of a substituted epoxide by LiAlH,, attack of the hydride ion occurs preferentially at the less hindered carbon of the epoxide, an observation consistent with reactivity. 

Much of our understanding of conformational analysis has arisen from studies on the reactions of rigid steroid nuclei. For example, the concept of trans-diaxial ring opening of epoxycyclohexanes was proposed to explain the stereoselective reactions seen with steroidal epoxides. Predict the product when each of the following steroidal epoxides is treated with LiAlH.. 

Anthracene is noncarcinogenic and is structurally incapable of forming a bay region diol epoxide. Anthracene 1,2-dihydrodiol is most conveniently synthesized from 2-anthranol by oxidation with phenylseleninic anhydride to anthracene 1,2-dione (55) followed by reduction with NaBH in ethanol (22) or LiAlH (55). Anthracene 1,2-dihydrodiol has also been synthesized via the Prdvost reaction route... 

Selective reduction of functional groups can be achieved by chemical modification of the LiALH4 for example, lithium tri(t-butoxy)aluminium hydride [LiAIH(t-OBu)3] is a more selective reagent, and reduces aldehydes and ketones, but slowly reduces esters and epoxides. Nitriles and nitro groups are not reduced by this reagent. Carboxylic acids can be converted into the aldehyde via acid chloride with lithium tri(tert-butoxy) aluminium hydride at a low temperature (—78°C). The nitro compounds are not reduced under this condition. Thus, selective reduction of 3,5-dinitrobenzoic acid (6.45) to 3,5-dinitrobenzaldehyde (6.47) can be achieved in two steps. First, 6.45 is converted into 3,5-dinitrobenzoyl chloride (6.46) and then LiAlH(t-OBu)3 reduction of 6.46 gives 6.47. 

The next stage of the synthesis was ring oxygenation, to convert 8 into 13. The key to this tr ansformation was the observation that the amide oxygen of 8 participated in the solvolysis of the allylic bromide, setting, after hydrolysis, the new secondary stereocenter of 9. Hydroxyl-directed epoxidation gave 10, which was rearranged with Ti(0-i-C,H,) to 11. After some experimentation, it was found that the derived dione 12 could be reduced to the desired cis diol 13 with LiBr and LiAlH(0-t-CjH,),followed by NaBH /CeCl,. 

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