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In contrast with the well‐established C(sp2)−SCF3 cross‐coupling to forge the Ar−SCF3 bond, the corresponding enantioselective coupling of readily available alkyl electrophiles to forge chiral C(sp3)−SCF3 bond has remained largely unexplored. We herein disclose a copper‐catalyzed enantioselective radical C(sp3)−SCF3 coupling of a range of secondary/tertiary benzyl radicals with the easily available (Me4N)SCF3 reagent. The key to the success lies in the utilization of chiral phosphino‐oxazoline‐derived anionic N,N,P‐ligands through tuning electronic and steric effects for the simultaneous control of the reaction initiation and enantioselectivity. This strategy can successfully realize two types of asymmetric radical reactions, including enantioconvergent C(sp3)−SCF3 cross‐coupling of racemic benzyl halides and three‐component 1,2‐carbotrifluoromethylthiolation of arylated alkenes under mild reaction conditions. It therefore provides a highly flexible platform for the rapid assembly of an array of enantioenriched SCF3‐containing molecules of interest in organic synthesis and medicinal chemistry. [ABSTRACT FROM AUTHOR]

Transition‐metal catalyzed enantioconvergent cross‐coupling of tertiary alkyl halides with ammonia offers a rapid avenue to chiral unnatural α,α‐disubstituted amino acids. However, the construction of chiral C−N bonds between tertiary‐carbon electrophiles and nitrogen nucleophiles presented a great challenge owing to steric congestion. We report a copper‐catalyzed enantioconvergent radical C−N cross‐coupling of alkyl halides with sulfoximines (as ammonia surrogates) under mild conditions by employing a chiral anionic N,N,N‐ligand with a long spreading side arm. An array of α,α‐disubstituted amino acid derivatives were obtained with good efficiency and enantioselectivity. The synthetic utility of the strategy has been showcased by the elaboration of the coupling products into different chiral α‐fully substituted amine building blocks. [ABSTRACT FROM AUTHOR]

The copper‐catalyzed enantioconvergent radical C(sp3)−C(sp2) cross‐coupling of tertiary α‐bromo‐β‐lactams with organoboronate esters could provide the synthetically valuable α‐quaternary β‐lactams. The challenge arises mainly from the construction of sterically congested quaternary stereocenters between the tertiary alkyl radicals and chiral copper(II) species. Herein, we describe our success in achieving such transformations through the utilization of a copper/hemilabile N,N,N‐ligand catalyst to forge the sterically congested chiral C(sp3)−C(sp2) bond via a single‐electron reduction/transmetalation/bond formation catalytic cycle. The synthetic potential of this approach is shown in the straightforward conversion of the corresponding products into many valuable building blocks. We hope that the developed catalytic cycle would open up new vistas for more enantioconvergent cross‐coupling reactions. [ABSTRACT FROM AUTHOR]

The intermolecular asymmetric radical oxidative C(sp3)−C(sp) cross‐coupling of C(sp3)−H bonds with readily available terminal alkynes is a promising method to forge chiral C(sp3)−C(sp) bonds because of the high atom and step economy, but remains underexplored. Here, we report a copper‐catalyzed asymmetric C(sp3)−C(sp) cross‐coupling of (hetero)benzylic and (cyclic)allylic C−H bonds with terminal alkynes that occurs with high to excellent enantioselectivity. Critical to the success is the rational design of chiral oxazoline‐derived N,N,P(O)‐ligands that not only tolerate the strong oxidative conditions which are requisite for intermolecular hydrogen atom abstraction (HAA) processes but also induce the challenging enantiocontrol. Direct access to a range of synthetically useful chiral benzylic alkynes and 1,4‐enynes, high site‐selectivity among similar C(sp3)−H bonds, and facile synthesis of enantioenriched medicinally relevant compounds make this approach very attractive. [ABSTRACT FROM AUTHOR]

In contrast to the wealth of asymmetric transformations for generating central chirality from alkyl radicals, the enantiocontrol over the allenyl radicals for forging axial chirality represents an uncharted domain. The challenge arises from the unique elongated linear configuration of the allenyl radicals that necessitates the stereo‐differentiation of remote motifs away from the radical reaction site. We herein describe a copper‐catalyzed asymmetric radical 1,4‐carboalkynylation of 1,3‐enynes via the coupling of allenyl radicals with terminal alkynes, providing diverse synthetically challenging tetrasubstituted chiral allenes. A chiral N,N,P‐ligand is crucial for both the reaction initiation and the enantiocontrol over the highly reactive allenyl radicals. The reaction features a broad substrate scope, covering a variety of (hetero)aryl and alkyl alkynes and 1,3‐enynes as well as radical precursors with excellent functional group tolerance. [ABSTRACT FROM AUTHOR]

The development of enantioconvergent cross‐coupling of racemic alkyl halides directly with heteroarene C(sp2)−H bonds has been impeded by the use of a base at elevated temperature that leads to racemization. We herein report a copper(I)/cinchona‐alkaloid‐derived N,N,P‐ligand catalytic system that enables oxidative addition with racemic alkyl bromides under mild conditions. Thus, coupling with azole C(sp2)−H bonds has been achieved in high enantioselectivity, affording a number of potentially useful α‐chiral alkylated azoles, such as 1,3,4‐oxadiazoles, oxazoles, and benzo[d]oxazoles as well as 1,3,4‐triazoles, for drug discovery. Mechanistic experiments indicated facile deprotonation of an azole C(sp2)−H bond and the involvement of alkyl radical species under the reaction conditions. [ABSTRACT FROM AUTHOR]

Radical‐involved enantioselective oxidative C−H bond functionalization by a hydrogen‐atom transfer (HAT) process has emerged as a promising method for accessing functionally diverse enantioenriched products, while asymmetric C(sp3)−H bond amination remains a formidable challenge. To address this problem, described herein is a dual CuI/chiral phosphoric acid (CPA) catalytic system for radical‐involved enantioselective intramolecular C(sp3)−H amination of not only allylic positions but also benzylic positions with broad substrate scope. The use of 4‐methoxy‐NHPI (NHPI=N‐hydroxyphthalimide) as a stable and chemoselective HAT mediator precursor is crucial for the fulfillment of this transformation. Preliminary mechanistic studies indicate that a crucial allylic or benzylic radical intermediate resulting from a HAT process is involved. [ABSTRACT FROM AUTHOR]

In contrast with the well‐established C(sp2)−SCF3 cross‐coupling to forge the Ar−SCF3 bond, the corresponding enantioselective coupling of readily available alkyl electrophiles to forge chiral C(sp3)−SCF3 bond has remained largely unexplored. We herein disclose a copper‐catalyzed enantioselective radical C(sp3)−SCF3 coupling of a range of secondary/tertiary benzyl radicals with the easily available (Me4N)SCF3 reagent. The key to the success lies in the utilization of chiral phosphino‐oxazoline‐derived anionic N,N,P‐ligands through tuning electronic and steric effects for the simultaneous control of the reaction initiation and enantioselectivity. This strategy can successfully realize two types of asymmetric radical reactions, including enantioconvergent C(sp3)−SCF3 cross‐coupling of racemic benzyl halides and three‐component 1,2‐carbotrifluoromethylthiolation of arylated alkenes under mild reaction conditions. It therefore provides a highly flexible platform for the rapid assembly of an array of enantioenriched SCF3‐containing molecules of interest in organic synthesis and medicinal chemistry. [ABSTRACT FROM AUTHOR]