Nickel catalyzed aryl-X - alkyl-X coupling from a new group

Looking through current organic methodology literature, we all see tons of 'copper-catalyzed this' and 'ligandless palladium-catalyzed cross-coupling' that and even now the onset of 'direct C-H functionalization' blablabla.  Of course that stuff is important, and my own methodology involves this kind of chemistry, but it's just a matter of fine-tuning all of the reaction conditions to work with the electronics of your particular substrate.  We are continuously hard-pressed to find truly general reaction conditions that we can throw at any ol' aryl halide and get coupling to form a C-C bond.

One of the issues with traditional cross-coupling reactions is preparing the cross-coupling partners; usually we try to mix R-X, with X being Cl (ideally), Br, I or OTf, with a second molecule that has to have a transmetallating group or otherwise activating group (boronic acid/ester, organocuprate generated in situ, etc.; see Sonogashira, Suzuki, Negishi, Buchwald-Hartwig or Hartwig-Buchwald coupling depending on who you talk to, and Stille, to name a few of these cross-coupling named reactions with preformed coupling partners).  Toss in some ligand, base, and transition metal complex and you've got a catalytic system for C-C bond formation.

To circumvent the necessity of this group, direct functionalization of an sp² C-H bond is becoming quite popular and works well for some substrates (see work of Lautens, the late Fagnou, Daugulis, Sames, Cheng, Bellina/Rossi, and Mori, just to name a few of the many).  This requires intense screening and optimization, however, and possibly requires directing groups; a few examples (linked to references) are arylation (popular), alkylation, cyanation, hydroxylation, and allylation.

The glory of JACS has recently given us R-X / R-X coupling between aryl iodides and alkyl iodides catalyzed by nickel reported by the brand new Weix group at the University of Rochester, "Nickel-Catalyzed Reductive Cross-Coupling of Aryl Halides with Alkyl Halides" (DOI: 10.1021/ja9093956).  The authors sought to find a system that minimized the common cross-coupling complications - homocoupling and/or reduction byproducts, having to use an excess of one of the coupling partners, and using a stoichiometric amount of a reagent required for the transmetallation.  Aryl and alkyl halides have been coupled before through organometallic intermediates like alkyl-ZnI or alkyl-MgBr, but the tolerance for acidic protons such as OH and the slow timescale of insertion by the Mn⁰ reductant provide evidence that the mechanism is more direct, without such an intermediate species.  Check out the paper for the decent substrate scope.

The reaction and conditions are as follows:

My favorite example?  The conditions tolerate a boronic ester which you DEFINITELY wouldn't get using palladium, so you can build your own reagent to be used in a future Suzuki.  Woohoo!  I look forward to the future publications of this group.