Lithium aluminum hydride reaction with ethylene

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... 

An efficient synthesis of ( )-quebrachamine is based on the construction of a suitable precursor via ring cleavage of an a-diketone monothioketal (810) (80JCS(P1)457). This monothioketal, available from 4-ethoxycarbonylcyclohexanone ethylene ketal, was fragmented to the dithianyl half ester (811) with sodium hydride in the presence of water. Reaction of (811) with tryptamine and DCC provided an amide which was converted to the stereoisomeric lactams (812) on hydrolysis of the dithiane function. Reduction of either the a- or /3-ethyl isomer with lithium aluminum hydride followed by conversion of the derived amino alcohol to its mesylate produced the amorphous quaternary salt (813). On reduction with sodium in liquid ammonia, the isomeric salts provided ( )-quebrachamine (814 Scheme 190). 

Evidence for the significant role of the alkoxyaluminohydride ions postulated by Trevoy and Brown11 4 has been secured experimentally by Fuchs and Vender Werf,w who examined the effect on product composition of altering the lithium aluminum hydride-ethylene oxide ratio. In the reaction of 1,2-epoxy-S-butene with approxinuuoU-stoichiometric quantities of reduoing agent, the principal product, l-buten-8-ol, was accompanied by a certain amount of the isomeric substance l-buten-4-ol (Eq, 374). The proportion of the latter mci[Pg.111]

The generation of the carbcxi-carbon double bond of unsaturated nitrogen heterocycles by the rDA reaction of cycloadducts that act as protected ethylenes has been accomplished. Azetines have been prepared by this method. Another example is the synthesis of l-methyl-3-pyrroline (201). By protecting the ethylene of N-methylmaleimide (199) with furan and then reducing with lithium aluminum hydride, adduct (200) was obtained (equation 86). Pyrolysis of adduct (200) at 250-300 C gave l-methyl-3-pyrroline (201) in 60% isolated yield. The ethylene moiety of N-substituted maleimides can also be generated via rDA reactions. Examples include the generation of N-phenylmaleimide (equation 87) and of N-acetoxymaleimide (equation 88). ... 

Hydroxyketones are versatile intermediates in the synthesis of pharmaceutical intermediates and heterocyclic molecules. a-Aryl hydroxyketones have been prepared by reaction of aryl aldehydes with 1,4-dioxane followed by reduction with lithium aluminum hydride (LAH) and by the selective LAH reduction of a-silyloxy a,P-unsaturated esters." WissneC has shown that treatment of acid chlorides with tris(trimethylsilyloxy)ethylene affords alkyl and aryl hydroxymethyl ketones. 1-Hydroxy-3-phenyl-2-propanone (3) has been generated by the osmium-catalyzed oxidation of phenylpropene and by the palladium-catalyzed rearrangement of phenyl epoxy alcohoP both in 62% yield. 

Reaction of ethylene diacrylate, which is commercially available, and subsequent reduction with lithium aluminum hydride gives endo-5-norbomene-2-methanol with 78 % ee. Although it is not clear why selectivity is increased by the link between di-enophiles, similar effects are expected for other asymmetric reactions (Eq. 38). 

This synthesis has been adapted to make the natural (5 -isomer of 114, reducing the initially formed aldehyde to (S)-114 with baker s yeast. [This same synthesis has been adapted to make (S)-callosobruchic acid (115), see below]. Julia s synthesis of a-geraniol (73) was also extended to make 114 by hydro-boration. Hydroboration of 73 with diisopinocampheylborane (made from (- )-a-pinene [(-)-116]) gave only a small ee however. A synthesis of ( )-114 started with the reaction of 2-methylpropiolactone and the ethylene acetal of 3-oxobutylmagnesium bromide. The methyl ester of the acid 117 thus prepared was chain-lengthened by reaction with acetylene and rearrangement with a vanadium catalyst of the ynol thereby obtained. The aldehyde 118 was then reduced with lithium aluminum hydride to 114. ... 

Reaction of that triketone with ethylene glycol selectively forms the expected 3,20-bisacetal the still free remaining ketone at Cn is next reduced with lithium aluminum hydride to yield the expected /8-hydroxyl group (11-1) (Scheme 7.11). Acid hydrolysis of the acetal groups followed by reaction with selenium dioxide generates the... 

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