Dr. Ciro Romano

Prof. Rubén Martín

Metal-catalyzed remote functionalization of aliphatic amines and amides triggered by photocatalytic sp3 C-H activation

From 01/06/2020 to

PHOTO-WALK

Activation of traditionally inert bonds has attracted great attention in the last decades and impressive advancements have been achieved in the catalytic functionalization of C-H bonds. Although the great number of catalytic methodologies for the transformation at sp2 C-H sites, manipulation of the corresponding sp3 C-H bonds remains largely confined to activated allylic and benzylic positions or to sites within reach of an existing directing group. Transition metal-catalyzed olefin isomerization has provided an outstanding tool for remote functionalization of sp3 C-H bonds but it requires the use of prefunctionalized molecules, bearing a pi component or an alkyl bromide. On the other hand, photocatalysis has emerged as a novel strategy for sp3 C-H activation but it is limited to the functionalization at the �� or ��positions with respect to a heteroatom. PHOTO-WALK will merge the photocatalytic activation of sp3 C-H bonds with a Ni-catalyzed chain-walking process, disclosing a completely novel triggering event for the remote functionalization of unactivated aliphatic amines and amides. The approach will overcome the limitations of current strategies for remote functionalization, allowing transformations at sp3 C-H sites unreachable by current photocatalytic methods and employing hydrocarbon feedstocks (aliphatic amines and amides) lacking of C=C or C-halide handles. Three functionalizations have been envisioned to increase molecular complexity by forging new C(sp2)–C(sp3) and C(sp3)–C(sp3) bonds: i) remote carboxylation, ii) remote arylation and iii) remote alkylation. PHOTO-WALK has the potential to be applied to the late-stage derivatization of pharmaceuticals, enabling the exploration of uncharted chemical spaces and offering the opportunity for structural diversification in drug discovery.