Mechanisms Complex-Induced Proximity Effect Process, Kinetically Enhanced Metalation, and Overriding Base Mechanism

1 Mechanisms Complex-Induced Proximity Effect Process, Kinetically Enhanced Metalation, and Overriding Base Mechanism 

SCHEME 26.2 Complex-induced proximity effect (CIPE) process. 

In agreement with this mechanism, a stopped-flow IR spectroscopic study on the metalation of iV,iV-dialkylbenzamides with s-BuLi/TMEDA [57] suggested the presence of amide-Li complex intamediates before the formation of the lithiated product. Theoretical (MNDO) evidence was also found for the formation of weakly chelated complexes suggesting that a coordination event leads to a deprotonation process [58,59]. Inter- and intramolecular kinetic isotope effect (KIE) studies also support a CIPE mechanism [60, 61]. 

An alternative scenario in which complexation of the base and proton abstraction occur simultaneously in a kinetically controlled one-step reaction was postulated by Schleyer (Fig. 26.4a) [13, 14]. In this kinetically enhanced metalation (KEM) model, this is not precomplexation that is important but the existence of a stabilizing metal-substituent interaction at the rate-limiting transition structures [13]. The fact that KIEs of inter- and intramolecular lithiation of anisole by -BuLi in Etp are identical (kjkj =2.5 0.2) [63] supports this one-step mechanism. 

Both theories furnish a complete picture if adequately put together (Fig. 26.4b) [62]. The directing and accelerating effect of the substituents is likely due to the stabilization of both the initial complex and the transition structure. Coordination by the DMG would be strongo- in the TS than in the initial complex. As a result, complexation would increase the rate of reaction by providing a new mechanism with lower activation energy E). 

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