Epoxides reaction with lithium aluminium hydrid

Grieco and his co-workers have completed a most notable total synthesis of /-quassin (130) (Scheme 3).1 The synthesis of the hydroxy-lactone (127) was outlined last year (see Vol. 11, p. 121). The conditions developed for the conversion of the bis-(a-hydroxy-ketone) (128) into the bis-(O-methyldiosphenol) (129) also achieved the crucial inversion of configuration at C-9.74 The close proximity of the C-7 oxygen atom to the C-ll carbon atom in the 9-epiquassin skeleton is evident from a series of reactions in which intramolecular participation occurs. Thus, for example, treatment of the epoxide (131) with lithium aluminium hydride gave the ether (132) whose structure and stereochemistry were established by A -ray analysis.75 Synthesis of the tetracyclic (133), a possible intermediate for quassinoid synthesis, involved the intramolecular cycloaddition of a quinonedimethane as the key step.78... 

Fucoxanthin (40) in a series of reactions involving lithium aluminium hydride reduction of the keto and acetate function to fucoxanthinol, allylic dehydration and subsequent epoxide rearrangement in acidic chloroform of fucoxanthinol to the epimeric fucochromes and further reaction with lithium aluminium hydride under forcing conditions, finally provided zeaxanthin (26) (22, 26). 

In this work the (i )-silyalkyne (125) was treated with lithium di-isopropylamide and methyl lithium and then the epoxide (126) was added. This gave the lactone (127) which with potassiiim hydroxide in ethanol produced the protected amino alcohol (128). Reaction of this compound with formalin afforded the cyclopentaoxazolidine (129) and this when heated with one molar equivalent of camphorsulphonic acid and chromatography yielded the indolizidine (130, R=Bn). Deprotection and oxidation under Swern conditions gave the aldehyde (131). Finally a Wittig reaction between this aldehyde and the ylide (132) produced the enone (133) which was reduced with lithium aluminium hydride to yield (+)-pumiliotoxin-B, together with a small amount (-6%) of its erythro-isomer (Scheme 6). 

The stereospecific synthesis of (20S,22R)-17a,20,22-trihydroxycholesterol (388) and its (20S,22S)-isomer (389) has been reported. Addition of vinyl Grignard reagent to the known 16a.l7a-oxidopregnenolone acetate (385), followed by opening of the epoxide with lithium aluminium hydride, furnished the 17,20-dihydroxy-intermediate (386). Conversion into the 3,5-cyclo-steroid (387) and epoxidation of the remaining double bond afforded a C-22 epimeric mixture of epoxides which, on reaction with s-butyl-lithium and reconversion into the 3jS-hydroxy-A -steroids, afforded the epimeric tetraols (388) and (389). The preparation of similar 3,17,20-triols is also reported. ... 

The product of the reaction with c/s-stilbene was a trichloroacetate ester which yielded the wcso-glycol upon reduction with lithium aluminium hydride the /raHs-olefin yielded the racemic glycol after the same treatment . Such reaction products are consistent with ring-opening of the epoxide by strong acid, and it was shown that (-)-rraHs-stilbene oxide reacted rapidly (relative to the rate of epoxidation) with trichloroacetic acid in benzene the overall observations are indicative of acid-catalysed epoxidation of stilbene but may admit other interpretations, one of which involves thermodynamic intervention of trichloroacetic acid dimer in a solvating capacity rather than in a truly kinetic function. 

Asymmetric Buchner reactions using chiral auxiliary have also been undertaken. The diazoketo substrate 126 for the chiral tethered Buchner reaction is prepared from optically pure (2/ ,4/f)-2,4-pentanediol in three steps the Mitsunobu reaction with 3,5-dimethylphenol, esterification with diketene, and diazo formation/deacetylation. Treatment of 126 with rhodium(II) acetate results in a quantitative yield of 127 with more than 99% ee. This compound is reduced with lithium aluminium hydride, and the resulting diol 128 undergoes epoxidation and concurrent acetal formation to give 129 as a single diastereomer. Hydrogenation of 129 with Raney nickel proceeds stereoselectively to yield saturated diol 130, which is converted to aldehyde 132 via acid hydrolysis followed by oxidation. Compound 132 is a versatile intermediate for natural product synthesis. 

An indication that the 14j8-hydroxyl is not essential for cardiotonic activity comes from the synthesis of 14-desoxy-14)8-uzarigenin. Lithium aluminium hydride reduction and acetylation of the 17 0 -epoxide obtained from the enol acetate (79) gave the 17/ -alcohol (80), which underwent a Serini-Logemann reaction to afford the 14 -pregnane (81). Reformatsky reaction with ethyl bromoacetate and dehydration gave the a -unsaturated ester (82), converted by selenium dioxide to 14-desoxy-14)8-uzarigenin (83). 

The sensitized photo-oxygenation of 5-methylene-4,7,7-trimethylcyclohepta-l,3-diene was found to give a mixture of the peroxide (233 36 %) and two aP-unsaturated ketones that were not identified (ketone yields = 3.5 % and 1 %). Several reactions of the peroxide (233) were studied, including thermal and photochemical conversion into the syn-bis-epoxide and the potassium hydroxide-methanol conversion into the hydroxyketone (234 X = O), which exists in equilibrium with its bicyclic hemi-ketal form. Lithium aluminium hydride reduction of peroxide (233) gave a mixture of the epimeric alcohols (234 X = H or OH). ... 

Lai er Rings.—Humulene A -monoepoxide (250) is the major product of WClg-n-butyl-lithium reduction of humulene triepoxide. It is reduced by lithium aluminium hydride or lithium-ethylamine to the 5-alcohol (251 X = OH, Y = H). The isomeric 4-alcohol (251 X = H, Y = OH) can be prepared from humulene-bis-epoxide. All -cis-cyclododeca-l,5,9-triene reacts with chlorosulphonyl isocyanate to give a good yield of mono-adduct, which can be hydrolysed to the p-lactam (252). Reactions of iV-bromosuccinimide in the presence of water, methanol, and acetic acid, with CIS- and trans-cyclododecene have been examined. cis- and trans-l-Nitrocyclo-dodecenes are interconverted on irradiation further irradiation causes isomerization to 3-nitro-trans-cyclododecene. ... 

Reaction of hexamethylDewarbenzene epoxide with a mixture of lithium aluminium hydride and oleum (= AIH3-SO3) followed by aqueous work-up gave a 95 5 ratio of the alcohols (577) and (578). Nucleophilic hydride attack on the epoxide is sterically hindered electrophilic hydride or associated Lewis acid attack on oxygen should facilitate epoxide cleavage leading to the cation (579), the precursor of the products. 

Oxymercuration followed by borohydride reduction of 6-methylenebicyclo-[3,l,l]heptane (166) gave the alcohols shown in Scheme 8. Similar reaction with 5-methylenebicyclo[2,l,l]hexane gave entirely monocyclic products. Stereochemical aspects are discussed for the formation and reduction of epoxides of 2-methylene- and 3-methylene-bicyclo[3,l,l]heptanes, the hydrobora-tion-oxidation of 3-methylenebicyclo[3,l,l]heptanes, and reduction by lithium aluminium hydride and diborane of bicyclo[3,l,l]heptanones. ... 

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