Ni-electrocatalytic Csp3–Csp3 doubly decarboxylative coupling

Nickel-Catalyzed C(sp3)–C(sp3) Cross-Electrophile Coupling of In Situ Generated NHP Esters with Unactivated Alkyl Bromides

“…Decarboxylative cross-coupling of unactivated alkyl carboxylic acids with unactivated alkyl bromides for the construction of C­(sp 3 )–C­(sp 3 ) bonds remains comparatively rare. − MacMillan and co-workers have reported two different multimetallic photoredox approaches in this area that are useful for 3°/1° and 2°/1° cross-coupling. Herein, we describe an important, complementary advance: a nickel-catalyzed cross-electrophile coupling of in situ generated NHP esters , with unactivated alkyl bromides that is effective for a variety of 1°/1 °C­(sp 3 )–C­(sp 3 ) linkages (Figure C)…”

Photocatalytic Deoxygenative Alkylation of C(sp3)−H Bonds Using Sulfonylhydrazones

“…3 Historically, alkyl-alkyl couplings have been challenging to accomplish, but in recent years significant progress has been achieved using transition-metal catalysis, particularly by exploiting nickel-based complexes. [4][5][6][7][8][9][10][11][12][13][14][15][16] These methods rely on the availability of prefunctionalized electrophiles (e.g., alkyl halides) and nucleophilic coupling partners (i.e., organometallic reagents), and often require high catalyst loadings, which necessitate energyintensive purification strategies to remove any trace metal impurities. 15 Alternatively, an attractive option to enable C(sp 3 )-C(sp 3 ) bond formation would be to use easily accessible reagents in the absence of any transition metals, which would also facilitate applications that require higher regulatory scrutiny, such as the late-stage functionalization of medicinally relevant compounds.…”

Decarboxylative Cross-Coupling: A Radical Tool in Medicinal Chemistry

“…To this end, several emerging horizons are beginning to surface that can capitalize on these versatile starting materials: for example, an electrochemically driven reductive double DCC for the synthesis of a multitude of structures via a convergent C­(sp 3 )–C­(sp 3 ) coupling (Figure ). , The ramifications for such a method to simplify retrosynthetic logic are enormous, as practically any carbon–carbon bond can be retrosynthetically cleaved with this transform. As an example, unnatural amino acid 8 was previously prepared in an eight-step sequence involving a pyridine hydrogenation-based strategy where no C–C bonds were forged .…”