Iron Catalyst Halide coupling

Martin, Padron, and coworkers have reported on the scope and limitations of the use of iron(lll) halides as effective catalysts in the coupling of alkenes or acetylenes with aldehydes to achieve a wide variety of useful synthetic transformations. All these reactions are shown in Scheme 10, which serves as a guide through the aliphatic C-C bond formation section [27]. 

Anhydrous iron(III) halides catalyse coupling of alkynes and aldehydes.211 Simple terminal alkynes, R CH, react with aldehydes, R2CHO, to give ( ,Z)-1,5-dihalo-1,4-dienes (55). In contrast, non-terminal arylalkynes give ( ,)-o, /3-unsaturated ketones. The catalysts also promote standard Prins cyclization of homoallylic alcohols. Studies of intermediates and of alkyne hydration - together with calculations - all support FeX3 complex formation with alkyne as the activating step. 

Fig. 2 Catalysts and ligands used in iron-catalyzed cross-coupling reactions with alkyl halides...

Cross coii ing of Grignard reagents with 1-alkenyl halides, in marked contrast to alkyl halides, occurs readily with the reduced iron catalyst, as described above. The iron-catalyzed reaction of Grignard reagents with 1-alkenyl halides can, however, be differentiated from the reaction with alkyl halides. Thus, a mixture of propenyl bromide and ethyl bromide on reaction with methylmagnesium bromide afforded butene-2 but no cross-over products such as pentene-2 or propylene. The latter certainly would have resulted if a propenyliron species per se were involved in the catalytic process. Cross coupling under tEese circumstances clearly merits further study. 

In some cases, vinyl halides can be coupled. An aryl Grignard reagent was coupled to a vinyl iodide in the presence of an iron catalyst.Butylmag-nesium chloride was coupled to vinyl triflates with Fe(acac)3. ° The palladium-catalyzed coupling of arylmagnesium halides and vinyl bromides has also been reported. ... 

Alkenyl halides couple readily with Grignard reagents in the presence of iron. -E n-Hexylmagnesium bromide allowed to react at 0° with vinyl bromide in tetrahydrofuran in the presence of FeClg 1-octene. Y 83%. F. e. s. M. Tamura and J. Kochi, Am. Soc. 93, 1487 (1971) also coupling with satd. halides in the presence of Ag - and Cu -catalysts s. Synthesis 1971, 303. 

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]. 

It has been established that Fe(II) complexes such as 74 and 75 are active catalysts in iron-catalyzed cross-couplings of alkyl halides (Figure 1.3) [347, 348]. The couplings probably involve a Fe(I)-Fe(III) cycle, in which radical intermediates in the coupling step can be excluded, although they might be involved in the oxidative addition step [349, 350]. 

The challenging issue in the cross-coupling of alkyl halides has been addressed with iron catalysts. Fe(acac)j in refluxing ether is a competent catalyst for the reaction between arylmagnesium bromides and both primary and secondary alkyl bromides. The cross-coupHng between para-tolylmagnesium bromide 44 and the alkyl bromide 107 illustrates the chemoselectivity of the process, as the triflate... 

Bromo- and iodoanihnes, -phenols and -benzoic acids are first deprotonated in situ by an excess of the organomagnesinm reagent and then coupled (PdCl2(dppf), 1 mol%, THF, 25 °C, 3 h) with organomagnesium halides, thus avoiding tedious protection-deprotection steps . Iron(in) salts can also serve as appropriate catalysts for varions cross-coupling... 

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