Emergent synthetic methods for the modular advancement of sp(3)-rich fragments

Fragment-based drug discovery is an important and increasingly reliable technology for the delivery of clinical candidates. Notably, however, sp(3)-rich fragments are a largely untapped resource in molecular discovery, in part due to the lack of general and suitably robust chemical methods available to aid their development into higher affinity lead and drug compounds. This Perspective describes the challenges associated with developing sp(3)-rich fragments, and succinctly highlights recent advances in C(sp(3))–H functionalisations of high potential value towards advancing fragment hits by ‘growing’ functionalised rings and chains from unconventional, carbon-centred vectors.