The catalytic radical-initiated asymmetric 1,2-aminosilylation of alkene with a hydrosilane under Cu(I)/CPA cooperative catalysis has been developed. This method features the use of hydrosilane as ...the reductive radical precursor, enabling efficient access to skeletally diverse silicon-containing azaheterocycles including pyrrolidine, indoline and isoindoline bearing an α-tertiary stereocenter with high enantioselectivity. The key to the success includes the use of Cu(I)/CPA cooperative catalyst system and the β-silicon effect of the silyl group to stabilize the
in situ
generated carbocation intermediate.
A general copper-catalyzed C(sp3)−C(sp2) cross-coupling of (hetero)benzyl bromides with the air- and moisture-stable aryl nucleophiles has been developed, providing a facile access to ...pharmaceutically useful 1,1-di(hetero)arylalkane and 1-aryl-1-heteroarylalkane scaffolds. Critical to the success is the utilization of a proline-based N,N,P-ligand to enhance the reducing capability of copper, thus easily converting benzyl bromides to the corresponding radical species via a single-electron transfer process under ambient conditions. The reaction features a broad substrate scope, covering (hetero)arylboronate esters, oxadiazoles, and benzodoxazoles, as well as primary and secondary (hetero)benzyl bromides with excellent functional group tolerance.
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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.
A copper‐catalyzed enantioselective radical C(sp3)−SCF3 coupling of secondary/tertiary benzyl radicals with the easily available (Me4N)SCF3 reagent was developed to afford enantioenriched trifluoromethylthiolated molecules. The key to the success lies in the utilization of chiral phosphino‐oxazoline‐derived anionic N,N,P‐ligands for the reaction initiation and enantioselectivity.
A copper-catalyzed enantioconvergent radical C(sp3)–N cross-coupling of racemic tertiary α-bromo-β-lactams with aromatic amines is developed under mild thermal reaction conditions. The use of a ...sterically demanded oxazoline-derived sulfonamide N,N,N-ligand is crucial for the reaction initiation and effective enantio-discrimination of the azetidinone-derived cyclic alkyl radicals. The strategy provides an attractive approach to access chiral α-amino-β-lactams, an important structural motif in many biologically active molecules. Preliminary mechanistic studies support the formation of azetidinone-derived alkyl radicals from the L*Cu(I)-amido complex and α-bromo-β-lactams.
The achiral ligand effect is utilized together with copper/phosphoric acid dual catalysis to achieve the first asymmetric radical oxytrifluoromethylation of alkene molecules with alcohols. In their ...Communication on page 8883 ff., X.‐Y. Liu et al. show that achiral pyridine units act as stabilizing ligands for transient copper intermediates in this novel transformation. The approach may find broad applications in related asymmetric processes.
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.
A copper‐catalyzed enantioconvergent radical C−N cross‐coupling of tertiary alkyl halides with sulfoximines (as ammonia surrogates) was realized by employing a chiral anionic N,N,N‐ligand with a long spreading side arm under mild conditions. An array of valuable α,α‐disubstituted amino acids could be furnished with good efficiency (up to 95 % yield) and enantioselectivity (up to >99 % ee).
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.
Radikalkontrolle: Die erste radikalische intramolekulare enantioselektive oxidative C‐H‐Aminierung von allylischen und benzylischen Substraten verläuft über einen Wasserstoffatomtransfer‐Prozess mit einem chiralen CuI/Phosphorsäure‐Katalysator. Entscheidend ist die Verwendung von 4‐Methoxy‐PINO als stabiler und chemoselektiver Wasserstoffabstraktor.
The copper‐catalyzed enantioselective radical difunctionalization of alkenes from readily available alkyl halides and organophosphorus reagents possessing a P−H bond provides an appealing approach ...for the synthesis of α‐chiral alkyl phosphorus compounds. The major challenge arises from the easy generation of a P‐centered radical from the P−H‐type reagent and its facile addition to the terminal side of alkenes, leading to reverse chemoselectivity. We herein disclose a radical 1,2‐carbophosphonylation of styrenes in a highly chemo‐ and enantioselective manner. The key to the success lies in not only the implementation of dialkyl phosphites with a strong bond dissociation energy to promote the desired chemoselectivity but also the utilization of an anionic chiral N,N,N‐ligand to forge the chiral C(sp3)−P bond. The developed Cu/N,N,N‐ligand catalyst has enriched our library of single‐electron transfer catalysts in the enantioselective radical transformations.
Copper‐catalyzed chemo‐ and enantioselective radical 1,2‐carbophosphonylation of styrenes from readily available alkyl halides and dialkyl phosphites is developed. The key to the success of the strategy lies in not only the proper choice of phosphorus reagents to suppress the reverse chemoselectivity but also the utilization of a chiral N,N,N‐ligand to forge chiral C(sp3)−P bond.