Halogen Bonding Initiated Difunctionalization of 1.1.1Propellane via Photoinduced Polarity Match Additions

• Published in: Angewandte Chemie International Edition p. e202411961
• Main Authors: Yi, Liang, Kong, Deshen, Prabhakar Kale, Ajit, Alshehri, Rawan, Yue, Huifeng, Gizatullin, Amir, Maity, Bholanath, Kancherla, Rajesh, Cavallo, Luigi, Rueping, Magnus
• Format: Journal Article
• Language: English
• Published: 28.08.2024
• ISSN: 1521-3773; 1521-3773
• DOI: 10.1002/anie.202411961

Bicyclo[1.1.1]pentane (BCP), recognized as a bioisostere for para-disubstituted benzene, has gained widespread interest in drug development due to its ability to enhance the physicochemical properties of pharmaceuticals. In this work, we introduce a photoinduced, halogen bonding-initiated, metal-free strategy for synthesizing various BCP derivatives. This method involves the generation of nucleophilic α-aminoalkyl radicals via halogen-bonding adducts. These undergo selective radical addition to [1.1.1]propellane, yielding electrophilic BCP radicals that subsequently participate in polarity-matched additions, culminating in the difunctionalization of bicyclopentane. The versatility and practicality of this metal-free approach are underscored by its broad substrate scope, which includes late-stage functionalization and a series of valuable transformations, all conducted under mild reaction conditions.Bicyclo[1.1.1]pentane (BCP), recognized as a bioisostere for para-disubstituted benzene, has gained widespread interest in drug development due to its ability to enhance the physicochemical properties of pharmaceuticals. In this work, we introduce a photoinduced, halogen bonding-initiated, metal-free strategy for synthesizing various BCP derivatives. This method involves the generation of nucleophilic α-aminoalkyl radicals via halogen-bonding adducts. These undergo selective radical addition to [1.1.1]propellane, yielding electrophilic BCP radicals that subsequently participate in polarity-matched additions, culminating in the difunctionalization of bicyclopentane. The versatility and practicality of this metal-free approach are underscored by its broad substrate scope, which includes late-stage functionalization and a series of valuable transformations, all conducted under mild reaction conditions.