Fully Automated Flow Protocol for C(sp3)-C(sp3) Bond Formation from Tertiary Amides and Alkyl Halides

Herein, we present a novel C(sp(3))-C(sp(3)) bond-forming protocol via the reductive coupling of abundanttertiaryamides with organozinc reagents prepared in situ fromtheir corresponding alkyl halides. Using a multistep fully automatedflow protocol, this reaction could be used for both library synthesisand target molecule synthesis on the gram-scale starting from bench-stablereagents. Additionally, excellent chemoselectivity and functionalgroup tolerance make it ideal for late-stage diversification of druglikemolecules.

Automated summary

Here, a new method is presented for the formation of C(sp(3))-C(sp(3)) bonds via the reductive coupling of abundant tertiary amides with organozinc reagents prepared in situ. A multistep fully automated flow protocol enables library synthesis and gram-scale target molecule synthesis starting from bench-stable reagents. The reaction also demonstrates excellent chemoselectivity and functional group tolerance, making it ideal for late-stage diversification of drug-like molecules.