LiAlH4, reaction with epoxides

Primary and secondary amines also react with epoxides (or in situ produced episulfldes >r aziridines)to /S-hydroxyamines (or /S-mercaptoamines or 1,2-diamines). The Michael type lddition of amines to activated C—C double bonds is also a useful synthetic reaction. Finally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-cylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH4 (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). 

Reaction with a hindered epoxide.l The trans-epoxide (1) of tetramethyllimonene is inert to KOH (130°), LiAlH4 (THF, 90°), and even lithium triethylborohydride. It is opened by aluminum isopropoxide (110°) to give 70 30 mixture of 2 and 3. Reaction with LDA is more selective and gives 2 in 95% yield. In contrast, reaction with N-lithioethylenediamine (1, 567 570) gives 3 in 90% yield. The 70 30 mixture of 2 and 3 is converted by N-lithioethylenediamine to the more stable isomer 3. 

The same reducing agents LiBHEt3 and LiAlH4 also react with epoxides in SN2-type reactions converting them into alcohols (Figure 14.35).The sterically less hindered C—O bond is attacked in asymmetric epoxides regioselectively. 

Episulfides can be converted to alkenes. However, in this case the elimination is syn, so the mechanism cannot be the same as that for conversion of epoxides. The phosphite attacks sulfur rather than carbon. Among other reagents that convert episulhdes to alkenes are Bu3SnH, certain rhodium complexes,LiAlH4 (this compound behaves quite differently with epoxides, see 19-35), and mel. The reaction of H2S/PPh3 and MeRe03 converts episulfides to alkenes. Episulf-oxides can be converted to alkenes and sulfur monoxide simply by heating. ... 

The epimeric 2-hydroxymethyl-5,6-exo-trimethylenenorbomanes on reaction with sulphuric acid in pentane yield 4-homoisotwistane (811). Seychellene, which possesses the homoisotwistane skeleton, on conversion to its unstable epoxide, which was stored in the presence of light and air before reduction with LiAlH4, was transformed into the abnormal oxidation product norseychelanol (812) a scheme based on dioxetan formation was proposed. Bromination or Koch-Haaf carboxylation of (811) produces the appropriate 3-substituted derivative, indicating that C-3 in (811) is at least as reactive as the 1-position in adamantane, while the 1- and 8-positions in (811) are unreactive. The 3-bromo-derivative (813) is solvolytically more reactive than 1-bromoadamantane, and reaction with sodamide in boiling toluene yielded the anti-Bredt olefin (815) which could be isolated in 52% yield (815) exhibited typical... 

In the other reactions with Cp2TiCl, Cp2TiCl2/LiAlH4 or CpTi(CO)2, the elimination of oxygen from epoxides gives alkenes, and elimination of oxygen from sulfoxide give a thioether [57]. As a reduction with low valence titanium compounds, for example, cis-olefin is prepared from disubstituted acetylene [57]. 

Hydride Transfer In some reactions, a hydride ion is transferred to or from the substrate. The reduction of epoxides with LiAlH4 is an example (10-85). Another is the Cannizzaro reaction (19-60). Reactions in which a carbocation abstracts a hydride ion belong in this category ... 

Further variations on the epoxyketone intermediate theme have been reported. In the first (Scheme 9A) [78], limonene oxide was prepared by Sharpless asymmetric epoxidation of commercial (S)-(-)- perillyl alcohol 65 followed by conversion of the alcohol 66 to the crystalline mesylate, recrystallization to remove stereoisomeric impurities, and reduction with LiAlH4 to give (-)-limonene oxide 59. This was converted to the key epoxyketone 60 by phase transfer catalyzed permanganate oxidation. Control of the trisubstituted alkene stereochemistry was achieved by reaction of the ketone with the anion from (4-methyl-3-pentenyl)diphenylphosphine oxide, yielding the isolable erythro adduct 67, and the trisubstituted E-alkene 52a from spontaneous elimination by the threo adduct. Treatment of the erythro adduct with NaH in DMF resulted... 

The cathodic cleavage of CX- to CH-bonds can be achieved with a variety of substituents X, such as Hal, NR3+, PR3+, OTos, or epoxides. Generally, good yields, a high potential selectivity, and often good stereoselectivities are encountered (see also Chapters) [117-123]. Chemical reactions for similar conversions, which are well worked out, especially with regard to yield and selectivity, are the reduction of tosylates with LiAlH4 and halides with... 

Thiol synthesis. A powerful flavor-impact constituent of grapefruit juice is 1 -p-menthene-8-thiol (3). It has been synthesized by reaction of thiourea with the epoxide I to give 2 followed by reduction with LiAlH4. 

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