Kolbe heterocoupling: An unexplored opportunity Limited a ✓ ✓ Whereas the oxidative approach to Kolbe couplings suffers from limited scope, we hypothesized that a reductive approach employing in-situ generated redox active esters (RAEs) in concert with a suitable transition metal catalyst might represent a milder and more practical alternative. The use of RAEs in Ni-catalyzed Negishi, Suzuki, and Kumada couplings is well documented 20-22 and served as the inspiration for this approach due to its robust and chemoselective nature. Most importantly, from the standpoint of synthetic design, such a reaction could dramatically simplify the routes to seemingly trivial molecules by democratizing access to intuitive 1e -disconnections (radical retrosynthesis, Figure ). 23 For instance, cyclobutane 1 has been prepared through a laborious 9-step route wedded to polar bond disconnections. 24 Computation is often touted as a magic-bullet to identify promising routes yet SciFinder TM -generated retrosynthesis provided similarly laborious or highly speculative options (See SI). In contrast, a reductive Kolbe crosscoupling could conceivably access 1 in a single step from commercial/readily available acid 3 and 4. Similarly, unnatural amino acid 2 has been prepared through a 7-step route 25 with SciFinder TMgenerated retrosynthesis offering no discernable improvement whereas a reductive Kolbe might offer one-step access from acid 5 and 6. The direct C-C bond formation between ubiquitous alkyl carboxylic acids has the potential to increase the ideality with which broad sections of chemical space are accessed.