Given the challenges posed by NOVOFLAT, we decided to focus on understanding the factors that contribute to C-C functionalization followed by sp3-sp3 bond-formation. To this end, we have found recently the following:
(1) We have reported a catalytic dual Ni/photoredox technology that demonstrates the ability of simple carbonyl compounds to promote a C-C bond-functionalization followed by sp3 coupling via the intermediacy of precursors amenable to photoexcitation. This technique demonstrates the ability of our approach by using simple carbonyl groups as latent nucleophiles for sp3-sp3 bond-forming reactions (Nature communications 2022, 13, 2394)
(2) Taking into consideration the above considerations, we have recently took these conceptions one step-further for enabling sp3-sp3 bond-forming reactions within the context of trifluoromethylation events via C-C bond-functionalization by combining the virtues of photoredox catalysis to generate open-shell species and the flexibility exerted by simple and readily available Cu catalysts to incorporate the trifluoromethyl group into sp3 backbones (Angew. Chem. Int. Ed. 2023, 62, e202214633). In addition to this, we have demonstrated that photoredox catalysis is a perfect vehicle to incorporate difluorinated backbones into sp3 architectures, constituting an opportunity to rapidly and reliably build up molecular backbones of interest in medicinal chemistry programs (Org. Lett. 2022, 24, 5109).
(3) We have demonstrated the main idea delineated in NOVOFLAT by taking ester derivatives from proline and being able to extrude carbon dioxide while forming a new sp3-sp3 bond. Interestingly, this technique can be promoted by either Ni/photoredox dual catalysis or by simple sulfinate salts under light irradiation. We are currently exploring the scope of the transformation and the results will be reported in due course. In addition, we have shown the viability of enabling C-C bond-functionalization on simple aminoacid derivatives (Synlett 2022, 33, 52).
(4) Following up our interest on the development of C-C bond-functionalization events by virtue of dual catalysis, we have recently taken the conceptions delineated in (1) and show the possibilities that this might have to build up other sp3 architectures. Specifically, we have shown the possibility of promoting a sp3 amination event by means of C-C bond-functionalization of carbonyl derivatives, offering a complementary reactivity mode to classical sp3 C-N bond-forming reactions that require the utilization of prefunctionalized organic halides or harsh reaction conditions (Angew. Chem. Int. Ed. 2023, 62, e202217386).
(5) The virtues of Ni catalysis and photoredox endeavors have been explored a bit further in our group for building up sp3-sp3 architectures. In particular we have found the possibility to promote b-fragmentation beyond the realm of C-C functionalization (reported by our group recently: J. Am. Chem. Soc. 2020, 142, 20594), but allowing the establishing of a technique capable of promoting unconventional sp3 C-O bond-cleavage as well, certainly an enormous step-forward for building up sp3 architectures from simple building blocks (J. Am. Chem. Soc. 2022, 144, 11558).
(6) We have showed that Ni-catalyzed bond-forming reactions can be effected at remote positions within an alkyl side chain by a striking dichotomy exerted by the ligand backbone, thus showing the potential that nickel catalysis might have for promoting bond-formation at positions that otherwise inaccessible by other metal-catalyzed approaches (J. Am. Chem. Soc. 2023, 145, 3869; ACS Catal. 2023, 13, 5538).
(7) A considerable step-forward in the implementation of NOVOFLAT has recently been accomplished in our group by the successful development of a catalytic intramolecular decarboxylative sp3 allylation of simple methyl esters, a reaction that is enabled by a non-classical radical-polar crossover mechanism (Angew. Chem. Int. Ed. 2023, 62, e202304084. Following up these conceptions, we have recently accomplished the main goal in NOVOFLAT that promotes a skeletal editing by means of an catalytic intermolecular decarboxylative event by intercepting radical intermediates with olefin acceptors (J. Am. Chem. Soc. 2025, 147, 16747).
