Silyl groups as a steering element in enantioconvergent, nickel-catalyzed C(spn)-C(spm) cross-coupling of racemic silylated/germylated electrophiles

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Enantioselective nickel catalysis involving radical intermediates is already a key technology for forging C(spn)-C(spm) bonds (w/ n = mainly 3 and m = 3, 2 and 1) in an enantioconvergent fashion. Starting from racemic electrophiles and a broad range of zinc-based nucleophiles, an impressive number of difficult bond formations has been realized in recent years. With our interest in silicon chemistry, we asked ourselves what the effect of silyl substitution in the electrophilic component would have on the course of those cross-coupling reactions. With regard to α-silylated alkyl halides, we found out that the silyl group enables enantioconvergent C(sp3)-C(sp3) coupling with primary alkylzinc reagents; the intermediacy of a silicon-stabilized radical was crucial. Moreover, the silyl group exerts a strong influence on the regioselectivity of conventional allylic substitutions, and we have been able to design enantioconvergent and regiocontrolled C(sp3)-C(sp3) couplings of silylated allyl electrophiles (allylic substitution) and C(sp2)-C(sp3) couplings of silylated propargyl electrophiles (propargylic substitution), respectively. These new methods allows for the enantioselective synthesis of otherwise difficult-to-make carbon skeletons with silyl groups as an additional handle for subsequent functional-group manipulation. This project builds on this preliminary success, aiming at essentially dozens of unprecedented transformations steered by a silyl group. Furthermore, a directing donor group tethered to the silicon atom could enhance the reactivity of the silylated electrophile or even reverse the regioselectivity of allylic and propargylic displacements. For example, the use of secondary (achiral and chiral) alkylzinc reagents or "tertiary" silylated electrophiles belongs to the goals of this long-term endeavor. The same approach will be applied to germyl groups to eventually synthesize enantioenriched, germanium-containing building blocks. Promising experiments have already confirmed the viability of this unusual extension of nickel catalysis, adding new synthetic tools to the less explored field of germanium chemistry. The silicon- and germanium-containing products will be translated back into carbon chemistry by mainly cross-coupling techniques.