Lithium hydride reaction with ethylene

The reduction of the lactone grouping of compound (119) required the preliminary protection of the two keto groups. Reaction with ethylene glycol formed the diketal, the controlled reduction of which with lithium aluminum hydride enabled the cyclohemiacetal (118) to be obtained. In itself, the reduction takes place with a high yield and the main difficulty is the deketalization of the extremely unstable compound (118). Consequently, the products of lithium aluminum hydride reduction were immediately acetylated with acetic anhydride to a mixture of the 21-mono-and 18,21-diacetates. Hydrolysis of this mixture with 90% acetic acid at 100 C led to the 21-acetate of dl -aldosterone (123). Deacetylation of the latter with potassium carbonate gave not only dl -aldosterone (124) with a yield of 50%, but also its 17o -epimer. Natural -aldosterone was obtained by the same route from the tZ-enantiomer of (119). By Wettstein s first method (Scheme 66), cZZ-aldosterone (124) was formed from Sarett s ketone (67) in 22 stages with an over-all yield of 1.7%. 

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... 

A synthesis of comblike organoboron polymer/boron stabilized imidoanion hybrids was examined via reactions of poly(organoboron halides) with 1-hexylamine and oligo(ethylene oxide) monomethyl ether and subsequent neutralization with lithium hydride (scheme 8). The obtained polymers (10) were amorphous soft solids soluble in common organic solvents such as methanol, THF, and chloroform. In the nB-NMR spectra (Fig. 11), neutralization of the iminoborane unit with lithium hydride... 

The course of these additions of lithium hydride resembles that found for the addition of borane (Nagase et al., 1980 Graham et al., 1981). With ethylene, the initial step is exothermic formation of a Jt-complex without barrier, then rate-determining transformation to the borane via a four-centre transition structure. In both the borane and lithium hydride additions, there is relatively little development of the new C—H bond with distances of 1.692 and 1.736 A respectively in the transition structures. When a carbanionic product is not formed, for example in the reaction of lithium hydride with cyclopropenyl cation yielding cyclopropene and lithium cation (Tapia et al., 1985), reaction again occurs via a hydride-bridged complex, but the C- H- -Li array remains nearly linear throughout the reaction. 

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). 

Other bases may be employed, e.g. lithium hydride, sodium hydride, sodium amide or sodium in ethylene glycol with sodium in ethylene glycol, the reaction is called the Bamford-Stevens reaction. Aldehyde tosylhydrazones (200) do not form dianions with organolithiums, but the reagent adds to the carbon-nitrogen double bond to give the dilithium derivative (201) which decomposes to the organolithium compound (202). 

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 1 appears to result solely in termination. In hydrogenolysis experiments with various chelates we have observed precipitation of lithium hydride in all cases at room temperature. Attempts to generate chelated LiH in situ by adding hydrogen during ethylene polymerization also caused a rapid, irreversible loss of activity. Since there is no evidence that lithium hydride can add to ethylene under moderate polymerization conditions, it is unlikely that any significant chain transfer occurs via this mechanism. Potassium alkyls readily eliminate olefin with the formation of metal hydride, and sodium alkyls do so at elevated temperatures (56). It was noted earlier that chelation of lithium alkyls makes them more like sodium or potassium compounds, so it is quite probable that some termination occurs by eliminating LiH. It is conceivable that this could be a chain transfer mechanism with more reactive monomers than ethylene because addition to lithium hydride would be more favorable. 

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... 

---