Quenching with lithium arenes

Various effective synthetic routes can be based on metallation of organic substrates with lithium arenes, obtained in situ from metallic lithium and an arene present in substoichio-metric amounts. Immediate quenching of the lithiated intermediates may be considered as a reduction reaction of the original substrate. Otherwise, further functionalization may be attained when using diverse electrophiles. Various examples of such processes follow (see also equation 69 in section VI.B.l). 

Dialkoxymethyllithium compounds, for example 2-lithio-l,3-dioxan (311), are generated in situ as shown in equation 69, either by reductive lithiation of a phenyl thioether with a lithium arene or by transmetallation of the corresponding trialkylstannyl compound. Subsequent quenching with electrophiles leads to the usual alkylated or functionalized species ... 

From the experimental point of view, reductive desulfonylations with alkali metal arene radical anion complexes require a large excess of the radical anion, very short reaction times at low temperatures, and must be run under an inert atmosphere. Sodium or lithium naphthalenides in tetrahydrofuran at —78° or lower temperatures are typical reaction conditions. Tetrahydrofuran solutions of lithium naphthalenide are dark green. This color is lost when the substrate is added and restored once the reaction is finished. Upon completion, the excess reagent is quenched with a saturated aqueous solution of ammonium chloride or low molecular alcohols such as methanol or ethanol. 

Elschenbroich (38) studied the metalation of di(benzene)chromium, using a 5 1 molar ratio of BuLi-TMEDA to this ir-arene complex. The extent and orientation of metalation were studied by mass spectrometry of the products after quenching with D20. A lithium substituent on dibenzenechromium strongly activates the molecule toward further meta-... 

The in situ quench (ISQ) technique [47] involves premixing of a hthium amide base (usually LDA or LTMP) and the electrophile at low temperature before addition of the arene. As soon as the orf/io-lithio anion forms, it can immediately react with the electrophile. The inverse addition protocol is equally productive, that is, a mixture of the arene and the electrophile is treated with a lithium amide base. The electrophile must be either unreactive to or react nondestructively with the lithium amide base, which therefore drastically limits useful base-electrophUe combinations. This concept was introduced by Martin for cyanobenzene deprotonation-sUylation sequences [47]. Low concentrations of aryllithiums lead to increased functional group tolerance. The ISQ technique was extended to a number of electrophiles that are compatible with lithium amide bases, including TMSCl, MejSnCl, B(OiPr)j [125, 126], benzaldehyde, Mel, EtI, and Me S. ... 

Electrophilic Trapping of Lithium Species. The deprotonation of arene or heteroarene species followed by quench with electrophiles is a general method for the introduction of functional groups in organic molecules. The arene moiety needs to be electron poor (i.e., thiazoles, imidazoles, pyridine (V-oxides, etc.). Possible electrophiles include sources of halogens, carbonyls, or sulfur. Phenylacetylenes can also be deprotonated with LiO/Bu and quenched with various aldehydes. ... 

The synthesis of an enantiomerically enriched chromium complex via asymmetric lithiation of a prochiral tricarbonyl(ri -arene)chromium complex using a chiral lithium amide base was first demonstrated in 1994 by Simpkins [88]. Arene complex 44 was treated with C2-symmetric chiral base ent-39 in the presence of TMSCl as an internal quench and silylated complex 45 was obtained in 84% ee (Scheme 24). 

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