Cross alkyl halides, nickel-catalyzed

The effect of the ligand on the stereochemical course of a reaction catalyzed by a transition metal compound can be significant. For example, in the nickel-catalyzed cross-coupling reactions of alkyl Grignard reagents and aryl halides, the effect of changing the ligands on the metal is summarized in Fig. 13 (66, 67). 

Transition metal-catalyzed cross-coupling reactions between vinyl organometallic compounds and unactivated alkyl halides that can be usually performed with palladium, nickel and cobalt are of particular synthetic interest [37-39]. Recently, the groups of Cahiez [48] and Cossy [49] concurrently reported the first iron-catalyzed reaction of alkenyl Grignard compounds with primary and secondary alkyl halides (X=Br, I) (Scheme 5.15). The two protocols basically differ in the iron source... 

Low-Valent Nickel-Catalyzed Cross-Coupling Reactions of Alkyl Halides 326... 

Fig. 21 Nickel-catalyzed reductive cross-coupling of aryl and alkyl halides...

Netherton MR, Fu GC. Nickel-catalyzed cross-couplings of unactivated alkyl halides and pseudohalides with organometallic compounds. Adv. Synth. Catal. 2004 346 1525-1532. 

Zhou, J., Fu, G. C. Cross-Couplings of Unactivated Secondary Alkyl Halides Room-Temperature Nickel-Catalyzed Negishi Ikyl Bromides and Iodides. J. Am. Chem. Soc. 2003,125, 14726-14727. 

A simple way to avoid toxic and intractable triorganotin waste is to use monoorganotin reagents that are much less toxic and less lipophilic. Unactivated secondary alkyl halides can be coupled with aryl-trichlorotin in a nickel-catalyzed Stille cross-coupling reaction" (e.g. Scheme 5.8.15). 

For a review of nickel-catalyzed cross-coupling reactions of unactivated alkyl halides/... 

Very recently, Hu [129] has shown that cross-coupling reactions of alicyclic alkyl halides with Grignard reagents catalyzed with nickel catalysts exhibit a remarkable diastereoselectivity which depends markedly on the structure of the catalyst. Nickamine (45) has better performance than a second catalyst, 46 bearing a bidentate amino-amido ligand. The influence of the catalyst structure suggests that the diastereoselectivity of the reaction originates in the coordination sphere of the metal, that is, after capture of the radical by the transient Ni(III) intermediate has taken place, as shown in Scheme 2.19. 

In 1998, Knochel reported that, in the presence of 4-trifluoromethylstyrene, [Ni(acac)2] efficiently catalyzed cross-couplings between polyfunctional arylzinc derivatives and alkyl halides possessing P-hydrogens (Equation 5.15). While the alkyl halides were limited to primary alkyl iodides, the scope of nickel catalysis was significantly expanded. The role of the electron-deficient olefin, 4-trifluoromethylstyrene, was proposed to accelerate the reductive elimination step by decreasing the electron density at the nickel center of an (alkyl) (aryl)nickel intermediate [18]. 

Kambe found that the selectivity could be improved by the use of conjugated diene additives in the nickel-catalyzed cross-couplings of primary alkyl halides or tosylates with various Grignard reagents [19]. Phenylmagnesium bromide can be used for arylations of primary alkyl bromides with [NiCl2] as catalyst and... 

Recently, bipyridines and amino alcohols, which were rather unique ligands for conventional nickel-catalyzed cross-coupling reactions, have been shown to be eflective for nickel-catalyzed arylations of secondary alkyl halides. Fu reported that a combination of [Ni(cod)2] and bathophenanthroline 13 catalyzed the cross-... 

In sharp contrast to the palladium- and nickel-catalyzed cross-couplings described above, iron catalysts show a high catalytic activity towards secondary alkyl halides, as reported by Nakamura and coworkers. Thus, cyclohexyl chloride, bromide or iodide can be arylated by a phenyl Grignard reagent in almost quantitative yield in the presence of FeCh as catalyst, along with an excess amount of a diamine additive N,N,N, N -tetramethylethylenediamine (TMEDA). Primary alkyl halides, such as octyl chloride, bromide and iodide, can also be arylated by the action of the same iron catalyst. However, the yields are somehow decreased, especially when primary alkyl chlorides are used as electrophiles (Equations 5.24 and 5.25) [33]. 

---