Lithium aluminum hydride Subject

It is preferable to use ether subjected to final drying by distillation from lithium aluminum hydride. 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

A rather complex fused isoindoline (87) has been found to show good anorectic activity. This substance differs from other anorectic agents by not being a p-phenethylamine analogue. Preparation of this compound starts by reaction of a substituted benzoyl-benzoic acid (82) with ethylene diamine. The product (84) can be rationalized as being the aminal from the initially obtained monoamide 83. This is then subjected to reduction with lithium aluminum hydride... 

When subjected to mercury acetate the ynone 78 underwent a 5-endo-dig cyclization and after work-up with aqueous sodium chloride, furnished the pyrrolinones 79 and 80 in a ratio of 89/11. The mixture of pyrrolinones was reduced directly with sodium borohydride to the iST-Boc-pyrrolidinol 81 which was obtained as a single diastereoisomer. Reduction of the carbamate with lithium aluminum hydride gave (+)-preussin (2) in 37% overall yield. 

Precursors of type E (erythro fragment) (Scheme 6.69) were obtained by cycloaddition of a nitrile oxide dipole to a-alkoxyalkenes. This strategy was used in the syntheses of dl- and D-lividosamine (298) (Scheme 6.73). Lithium aluminum hydride reduction of the erythro adduct 130 produced aminoalcohols 135 in a 78 22 ratio (2,4-erythro/threo) in high yield. The mixture was subjected to HC1 hydrolysis to give the hexosamine hydrochlorides 136, which after several steps, produced D-lividosamine 137 possessing the D-ribo configuration (298). 

Reactions of 4,7-phenanthroline-5,6-dione have been the subject of considerable study. It is reduced to 5,6-dihydroxy-4,7-phenanthroline by Raney nickel hydrogenation226,249 or by aromatic thiols in benzene,262 and oxidized by permanganate to 3,3 -bipyridyl-2,2 -dicarboxylic acid.263 It forms bishemiketals with alcohols226 and diepoxides with diazomethane.226 The diepoxides by reaction with hydrochloric acid form diols of type 57, R = Cl, which on oxidation with lead tetraacetate give 3,3 -bipyridyl diketones of type 58, R = Cl. Methyl ketones of type 58, R = H, are also obtained by lead(IV) acetate oxidation of the diol 57, R = H, obtained by lithium aluminum hydride reduction of 57, R = Cl. With phenyldiazomethane and diphenyldiazomethane the dione forms 1,3-dioxole derivatives,264,265 which readily hydrolyze back to the dione with concomitant formation of benzaldehyde and benzophenone, respectively. 

Only the trifluoromethyl group has been subjected to reduction in this class of compound. Although not reduced by zinc in acetic acid or by sodium in ethanol, diethyl 2-methyl-4-(tri-fluoromethyl)-1//-pyrrole-3,5-dicarboxylate (1) is reduced at the trifluoromethyl group with an excess of lithium aluminum hydride to give the corresponding tetramethyl derivative 2 sodium borohydridc in ethanol is quite inefficient.104... 

The heterocyclic ring of indole is not subject to nucleophilic attack and undergoes no reduction with lithium aluminum hydride or... 

Our attention was first called to the possibility of sintering at room temperature some five or six years ago, when we found that lithium aluminum hydride was as transparent as glass after having been subjected to a pressure of 100,000 atm. 

The perhydro-isoxazolo[2,3-fl]pyridine system offers a route to 2,6-disubstituted piperidines. For example, the reaction between styrene and the substituted 3,4,5,6-tetrahydropyridine-l-oxide (69) gives the isoxa-zolidine (70) which, on benzylation, gives 71. This was subjected to reductive cleavage of the N—O bond with lithium aluminum hydride, followed by mesylation of the aminodiol produced. Treatment of the mesylate with lithium triethylborohydride gave the trans-2,6-disubstituted piperidine... 

The synthesis of the novel tetrafuran-containing macrocycle 4.178 was reported in 1992. This macrocycle was prepared by the aldol-type condensation between diketone 4.176 and dialdehyde 4.177 in 20% yield (Scheme 4.5.2). Subjecting this macrocycle to reductive deoxygenation using lithium aluminum hydride and aluminum trichloride afforded the tetraoxaporphyrinogens-(3.0.3.0) 4.179 and 4.180 in combined 35% yield (Scheme 4.5.3). These two isomeric products, formed in 55% and 45% relative abundance, respectively, could not be readily separated. Instead, they were treated together (i.e., as a mixture) with p-chloranil to afford the conjugated tetraoxa[22]porphyrin-(3.0.3.0) species 4.181 in 15% yield (Scheme 4.5.4). 

All these results are consistent with the 8-lactam structures CCCXCVI and CCCXCVII which received confirmation by conversion of the amino alcohol CCCC to CCCCIII and unambiguous synthesis of the latter from CCCXCVIII. The monotosylate of the methylated diol CCCCI was subjected to reduction with lithium aluminum hydride to give the base CCCCIII. Reaction of the amino alcohol CCCXCVIII with methyl... 

Sodium borohydride and potassium borohydride react regioselectively with the formyl group of alkyl 2-formylcyclopropanecarboxylates lithium aluminum hydride is unseleetive. Stereospecific reduction of the formyl group was observed when formyl-cyclo-propanes were subjected to yeast alcohol dehydrogenase. ei Furthermore, regiospecific reduction of the aldehyde function in a 2-cyclopropylprop-2-enal derivative was performed using a mixture of sodium borohydride and cerium(III) chloride. 

The stereoselectivity of the hydride reduction of conjugated cyclohexenones has also been subjected to close examination from both experimental and theoretical viewpoints. Much of the work has involved polycyclic systems, e.g.. steroids which have little conformational flexibility and in which axial and equatorial directions of approach can be clearly defined. With small" hydride donors, these substrates show an even clearer preference for axial attack than the corresponding cyclohexanones. For examples involving reductions with lithium aluminum hydride and sodium borohydride, see Table 10. 3/(-Acetylcholest-5-en-7-one and cholest-2-en-l-one are notable in that the analogous saturated substrates are attacked from the equatorial direction115 l16. The reduction of 17/i-hydroxy-4-androsten-3-one (testosterone) to 4-androstene-3/1,17/j-diol with d.r. 90 10 can be compared with the sodium borohydride reduction of 17/i-hy-droxyandrostan-3-one (dihydrotestosterone) to androstane-3/ ,17/ -diol with d.r. 81 19 (see p 4030). 

The sequence of reactions nicely points out the relative reactivity of carbonyl groups at positions 3, 11 and 17. Reaction of the triketone 29-2 with a controlled amount of pyrrolidine leads to the formation of the enamine from the most reactive ketone, that at C3 (30-1) (Scheme 5.30). Treatment of this intermediate with methylmagnesium bromide leads to exclusive addition to C17. Although the ketone at Cn is virtually inert to addition reactions, it is subject to reduction. Reaction of 30-2 with lithium aluminum hydride thus leads to the corresponding j8-hydroxy derivative. The enamine is then removed by acid hydrolysis (30-4). Reaction of the newly formed alcohol with /i-toluenesulfonyl... 

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