Abstract
A Cu-catalyzed strategy has been developed that harnesses a radical relay mechanism to intercept a distal C-centered radical for C-C bond formation. This approach enables selective δ C-H (hetero)arylation of sulfonamides via intramolecular hydrogen atom transfer (HAT) by an N-centered radical. The radical relay is both initiated and terminated by a Cu catalyst, which enables incorporation of arenes and heteroarenes by cross-coupling with boronic acids. The broad scope and utility of this catalytic method for δ C-H arylation is shown, along with mechanistic probes for selectivity of the HAT mechanism. A catalytic, asymmetric variant is also presented, as well as a method for accessing 1,1-diaryl-pyrrolidines via iterative δ C-H functionalizations.
Highlights
The remote C–H functionalization of amines via intramolecular hydrogen atom transfer (HAT) has enabled a distinct approach to the synthesis of pyrrolidines for over a century.1,2 Yet, while this formal d C–H amination has been interrupted to afford distal halogenation and oxygenation, it has rarely enabled d C–C bond formation.3–5 A mechanistic explanation is that initiation of this radical rearrangement requires homolysis of an N-halo amide to generate the N-centered radical (Fig. 1a)
In designing a strategy to enable the rst d C–H arylation via a radical relay mechanism,11–14 we proposed a Cu catalyst could
Control experiments reveal that both bisoxazoline ligand (Æ) L1 and an aryl boronic acid are necessary for efficient amide consumption, suggesting the Cu complex requires both donating ligands to reduce the N–F
Summary
The remote C–H functionalization of amines via intramolecular hydrogen atom transfer (HAT) has enabled a distinct approach to the synthesis of pyrrolidines for over a century.1,2 Yet, while this formal d C–H amination has been interrupted to afford distal halogenation and oxygenation, it has rarely enabled d C–C bond formation.3–5 A mechanistic explanation is that initiation of this radical rearrangement requires homolysis of an N-halo amide to generate the N-centered radical (Fig. 1a). This approach enables selective d C–H (hetero)arylation of sulfonamides via intramolecular hydrogen atom transfer (HAT) by an N-centered radical. The radical relay is both initiated and terminated by a Cu catalyst, which enables incorporation of arenes and heteroarenes by cross-coupling with boronic acids.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
