Synthesis hthium amides

Fluorides are more reactive than the other hahdes, (cf. 3.3.2) for example 2-fluoropyridine can be converted into 2-dialkylamino-pyridines using hthium amides at room temperature. This could be compared with the 130 °C required to displace a-bromine using the potassium salt of pyrazole. Displacement of nitro can be made the means for the synthesis of a- and y-fluoro-pyridines. Of the five fluorines in pentafluoropyridine, the y-fluorine is displaced most rapidly. ... 

A hindered Hthium amide such as lithium 2,2,6,6-tetramethylpiperidide (LTMP) has proved to be effective in triggering a direct intramolecular cyclopropanation of the unsaturated terminal epoxide 31 to the tricycHc alcohol 32 (2010JOC2157). This strategy has been used successfully in a concise synthesis of (—)-cubelol (33) from (—)-menthone. Similarly, the naturally occurring (—)-10-epicubelol (34) can be prepared from (+)-menthone. Interestingly, whatever is the stereochemistry of the tethered alkene, the facial selectivity of cyclopropanation is controlled solely by the epoxide stereochemistry (Scheme 8). 

Iminoboianes have been suggested as intermediates in the formation of compounds derived from the pyrolysis of azidoboranes (77). The intermediate is presumed to be a boryl-substituted nitrene, RR BN, which then rearranges to the amino iminoborane, neither of which has been isolated (78). Another approach to the synthesis of amino iminoboranes involves the dehydrohalogenation of mono- and bis(amino)halobotanes as shown in equation 21. Bulky alkah-metal amides, MNR, have been utilized successfully as the strong base,, in such a reaction scheme. Use of hthium-/i /f-butyl(ttimethylsilyl)amide yields an amine, DH, which is relatively volatile (76,79). 

In 1988 Cox and Robinson also reported a synthesis of the 1,2,3,4-tetrahy-dro-9a,4a-(iminoethano)-9H-carbazole core (Scheme 2). Starting with the cyclohexanone 87 and the phenylhydrazine 88, they first formed hydra-zone 89 via heating in mixture of benzene and catalytic amounts of acetic acid at reflux, while removing water with a Dean—Stark trap. A Fischer indolization sequence was next achieved via heating the derived hydrazone 89 at reflux in acetic acid to furnish indolenine 90. Aqueous ammonia was then added to the crude product to perform a nucleophihc attack at both the ester carbonyl and indolenine imine carbon to eHcit precipitation of pyrro-hdinone 91. Finally, reduction of the amide employing hthium aluminum hydride in hot tetrahydrofuran (THF) provided pyrroloindole 92. 

The double hydroformylation strategy developed by Airiau et al. in their approach to the synthesis of (+)-lupinine ent-926) (c Scheme 132 Section 4.6.3) was also successfully appHed to their synthesis of (+)-epiquinamide (2104) (Scheme 276). This route commenced with Cbz-protected L-methionine (2184), aUylation of which via the Weinreb amide (—)-2185 produced ketone (+)-2186. Reduction of the ketone was accomplished with hthium tri(ferf-butoxy)aluminum hydride to afford alcohol (-)-2187 in excellent yield (94%) and a diastereoselectivity of greater than 98%. The sulfide, having served to disguise the second alkene, was then removed by oxidation to the sulfoxide followed by thermal elimination. The relative configuration of the product (—)-2188 was confirmed... 

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