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1. N-Directed fluorination of unactivated Csp ³ –H bonds

   https://doi.org/10.1039/C9SC04055B  

   Pinter, Emily N.; Bingham, Jenna E.; AbuSalim, Deyaa I.; Cook, Silas P. (January 2020, Chemical Science)

   Site-selective fluorination of aliphatic C–H bonds remains synthetically challenging. While directed C–H fluorination represents the most promising approach, the limited work conducted to date has enabled just a few functional groups as the arbiters of direction. Leveraging insights gained from both computations and experimentation, we enabled the use of the ubiquitous amine functional group as a handle for the directed C–H fluorination of Csp 3 –H bonds. By converting primary amines to adamantoyl-based fluoroamides, site-selective C–H fluorination proceeds under the influence of a simple iron catalyst in 20 minutes. Computational studies revealed a unique reaction coordinate for the catalytic process and offer an explanation for the high site selectivity. 

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2. Construction of congested Csp ³ –Csp ³ bonds by a formal Ni-catalyzed alkylboration

   https://doi.org/10.1039/d1sc00900a  

   Simlandy, Amit Kumar; Sardini, Stephen R.; Brown, M. Kevin (April 2021, Chemical Science)

   null (Ed.)

   Through the combination of a Ni-catalyzed alkene alkenylboration followed by hydrogenation, the synthesis of congested Csp 3 –Csp 3 -bonds can be achieved. Conditions have been identified that allow for the use of both alkenyl-bromides and -triflates. In addition, the hydrogenation creates another opportunity for stereocontrol, thus allowing access to multiple stereoisomers of the product. Finally, the method is demonstrated in the streamlined synthesis of a biologically relevant molecule. 

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3. Ligand‐Enabled δ‐C(sp ³ )−H Borylation of Aliphatic Amines

   https://doi.org/10.1002/anie.202105204  

   Chandrashekar, Hediyala B.; Dolui, Pravas; Li, Bijin; Mandal, Astam; Liu, Hao; Guin, Srimanta; Ge, Haibo; Maiti, Debabrata (July 2021, Angewandte Chemie International Edition)

   Abstract Directed C−H functionalization has been realized as a complimentary technique to achieve borylation at a distal position of aliphatic amines. Here, we demonstrated the oxidative borylation at the distal δ‐position of aliphatic amines using various borylating agents, a palladium catalyst, and a rightly tuned ligand in the presence of a cheap oxidant. Moreover, an organopalladium δ‐C(sp³)‐H‐activated intermediate has been isolated and crystallographically characterized to get mechanistic insight. 

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4. Transition-metal-free C(sp ³ )–H/C(sp ³ )–H dehydrogenative coupling of saturated heterocycles with N -benzyl imines

   https://doi.org/10.1039/D0SC00031K  

   Liu, Zhengfen; Li, Minyan; Deng, Guogang; Wei, Wanshi; Feng, Ping; Zi, Quanxing; Li, Tiantian; Zhang, Hongbin; Yang, Xiaodong; Walsh, Patrick J. (January 2020, Chemical Science)

   A unique C(sp 3 )–H/C(sp 3 )–H dehydrocoupling of N -benzylimines with saturated heterocycles is described. Using super electron donor (SED) 2-azaallyl anions and aryl iodides as electron acceptors, single-electron-transfer (SET) generates an aryl radical. Hydrogen atom transfer (HAT) from saturated heterocycles or toluenes to the aryl radical generates alkyl radicals or benzylic radicals, respectively. The newly formed alkyl radicals and benzylic radicals couple with the 2-azaallyl radicals with formation of new C–C bonds. Experimental evidence supports the key hydrogen-abstraction by the aryl radical, which determines the chemoselectivity of the radical–radical coupling reaction. It is noteworthy that this procedure avoids the use of traditional strong oxidants and transition metals. 

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5. Iron-catalyzed C(sp ² )–C(sp ³ ) cross-coupling at low catalyst loading

   https://doi.org/10.1039/C8CY02374C  

   Bisz, Elwira; Kardela, Marlena; Piontek, Aleksandra; Szostak, Michal (March 2019, Catalysis Science & Technology)

   The iron-catalyzed C(sp 2 )–C(sp 3 ) cross-coupling provides a highly economical route to exceedingly valuable alkylated arenes that are widespread in medicinal chemistry and materials science. Herein, we report an operationally-simple protocol for the selective C(sp 2 )–C(sp 3 ) iron-catalyzed cross-coupling of aryl chlorides with Grignard reagents at low catalyst loading. A broad range of electronically-varied aryl and heteroaryl chlorides underwent the cross-coupling using challenging alkyl organometallics possessing β-hydrogens with high efficiency up to 2000 TON. A notable feature of the protocol is the use of environmentally-friendly cyclic urea ligands. A series of guidelines to predict cross-coupling reactivity of aryl electrophiles is provided. 

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