Intermolecular Negishi reaction

Vedejs utilized a Negishi reaction in synthesizing the core of aziridinomitosene A. The C5 position of a C2-substituted oxazole was lithiated and transmetalated with ZnCh. The 5-oxazolylzinc chloride was utilized in an intermolecular Negishi reaction with a vinyl triflate in 70% yield with no reported intramolecular reaction at the alkyl iodide. ... 

Larhed, M. and Hallberg, A. Scope, mechanism, and other fundamental aspects of the intermolecular Heck reaction. In Negishi, E.-i., (Ed.) Handbook ofOrganopalladium Chemistry for Organic Synthesis, Wiley sons Inc., New York, 2002, Vol 1, pp. 1133-1178. 

A number of interesting one-pot or two-pot sequences of Pdarylation processes [14]. For example, a two flask sequence of Negishi coupling followed by intramolecular C—N bond formation has been employed for the synthesis of substituted indolines (Eq. (1.4)) [14a]. Lautens has recently described an elegant one-flask sequence of intermolecular C H bond functionalization followed by intramolecular N-arylation for the preparation of substituted indolines [14b]. As shown below (Eq. (1.5)), the Pd-catalyzed coupling of 2-iodotoluene with 2-bromopropylamine 5 in the presence of norbornene provided indoline 6 in 55% yield. 

In addition to intermolecular reactions, intramolecular variants have been developed. In 1992, Negishi et al. reported the Pd(PPh3)4/AcOH-catalyzed intramolecular [2 -I- 2 -I- 2] cycloaddition of triyne 12 (Scheme 6.4) [9]. In this reaction, cascade-type cycloaddition via generation of Pd—H species from palladium and acetic acid proceeded to afford fused benzene 13 in good yield. The reaction of endiyne 14 bearing an alkenyl bromide moiety in the presence of EtsN also afforded the same product, 13, presumably through a similar mechanism (Scheme 6.4). 

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