External and In Situ Quench Conditions

Under conventional external quench (EQ) conditions, the aiene and the base are premixed prior to addition of the electrophile. In general, the thermodynamic equilibrium existing between the anions intermediately formed is displaced toward the most stable (less basic) anion owing to its stabilization by the substituents (Fig. 26.7). 

External quench (EQ) — Thermodynamic product In situ quench (ISQ) — Kinetic product 

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.  

A silylation step is interposed between the first, second, and third hydrogen-lithium exchange in other words, the threefold electrophilic substitution is mediated by monometalated intermediates [128]. 

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