Selective Cross-Coupling of Organic Halides with Allylic Acetates

Abstract

A general protocol for the coupling of haloarenes with a variety of allylic acetates is presented. Strengths of the method are a tolerance for electrophilic (ketone, aldehyde) and acidic (sulfonamide, trifluoroacetamide) substrates and the ability to couple with a variety of substituted allylic acetates. Secondary alkyl bromides can also be allylated under slightly modified conditions, demonstrating the generality of the approach. Finally, the coupling of a reactive vinyl halide could be achieved by the use of a very hindered ligand and more reactive, branched allylic acetates.

Nickel-Catalyzed Reductive Couplings

“…While most transformations based on activated alkyl electrophiles emphasize C(sp 3 )-C(sp 2 ) bond forming methods (see Sects. 2.2-2.5), the cross-coupling of allylic acetates (or carbonates) with unactivated alkyl halides represents the only example for the construction of hetero C(sp 3 )-C(sp 3 ) bonds utilizing activated alkyl electrophiles [36][37][38].…”

“…The Ni-catalyzed reductive coupling protocol enables allylation of a wide set of alkyl halides (Scheme 10) [36][37][38]. The reactions display excellent regioselectivities wherein addition of alkyl groups to the less hindered allylic positions is adopted.…”

“…For instance, cyclohexyl bromide generally gives low-tomoderate yields as opposed to good results for the functionalized secondary alkyl substrates [36]. While Gong's conditions are more effective for secondary alkyl halides, Weix's method accommodates primary alkyl bromides when coupling with 1-aryl-decortated allylacetates [36,37]. The reactivity of the alkyl halides is tunable…”

“…Therein, oxidative addition of ArX to Bn-Ni I results in the key Ar-Ni III (X)-Bn intermediate [52]. While electrochemical arylation and vinylation of a-chloroketones and esters, as well as allyl acetates are well established [35], the equivalent chemical reduction methods have been documented for arylation of a-chloroesters (Scheme 21) [60] and allylic acetates [37,61]. The allylation of aryl halides is generally efficient for both electron-deficient and -rich arenes, which display excellent regioselectivities by the addition of aryl groups to the less-hindered allylic terminals (Scheme 22) [37,61].…”

Cross‐Electrophile Coupling of Vinyl Halides with Alkyl Halides

“…Previously reported conditions have required stoichiometric additives (MgCl 2 , pyridine), long reaction times (24 h), or higher temperatures (40–80 °C), even with relatively high catalyst loadings (7–10 mol% nickel). [4b, 6] During our mechanistic studies, [5] we had found that the addition of TMS-Cl to the metallic reductant (Mn powder) accelerated the rate of cross-electrophile coupling reactions while maintaining selectivity at a given catalyst concentration. [7] We report here modified conditions that allow the selective coupling of a variety of vinyl bromides with primary and secondary alkyl halides.…”