Negishi cross coupling Scope

Phapale VB, Cardenas DJ (2009) Nickel-catalyzed Negishi cross-coupling reactions scope and mechanisms. Chem Soc Rev 38 1598-1607... 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

Negishi, E., Takahashi, T., Baba, S., Van Horn, D. E., Okukado, N. Nickel- or palladium-catalyzed cross coupling. 31. Palladium- or nickel-catalyzed reactions of alkenylmetals with unsaturated organic halides as a selective route to arylated alkenes and conjugated dienes scope, limitations, and mechanism. J. Am. Chem. Soc. 1987,109, 2393-2401. 

The scope of the Negishi reaction is broad, similar to that of Stille and Suzuki cross-coupling. The reaction seems to work if R = aryl, vinyl, alkynyl, acyl, allyl, benzyl, homoallyl (-CH2-CH2-CH=CH2) and homobenzyl (-CH2-CH2-Ph), or even primary alkyl, and if X = I, Br, or OTf (Cl works, but often sluggishly). Correspondingly, R = aryl, vinyl, alkynyl, allyl, benzyl, and primary alkyl. The organozinc reagent may either be used as a preformed compound, such as R2Zn... 

Palladium-catalyzed cross-coupling reactions have received an enormous amount of attention among the synthetic chemists, and their scope has been very significantly expanded during the last several years. This chapter will deal with Kumada-Corriu, Stille, Negishi, Sonogashira, and Mipura-Suzuki ... 

The synthetic scope and utility of the Pd- or Ni-catalyzed aryl-aryl couphng may be most vividly appreciated by noting numerous examples of its application to natural product syntheses. In Table 3.4, only some representative examples of those that involve the use of Negishi coupling are Hsted. The bold Hnes shown in the target structures indicate the points of cross-couphng. 

The use of the well-defined PEPPSI-IPr precatalyst led to a significant improvement with respect to the rate and the substrate scope of the Negishi alkyl-alkyl coupling reactions (Scheme 3.62). This precatalyst can also be used to promote the cross-couphng of alkyl or aryl halides and sulfonates with arylzinc chloride reagents at room temperature by judicious choice of the solvent and additive (LiCl or LiBr) [236]. 

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