CaltechAUTHORS
Published November 9, 2022 | Version v2
Journal Article Open

Enantioselective Synthesis of N-Benzylic Heterocycles by Ni/Photoredox Dual Catalysis

Creators

  • 1. ROR icon California Institute of Technology

Abstract

An asymmetric cross-coupling of α-N-heterocyclic trifluoroborates with aryl bromides using Ni/photoredox dual catalysis has been developed. This C(sp²)–C(sp³) cross-coupling provides access to pharmaceutically relevant chiral N-benzylic heterocycles in good to excellent enantioselectivity when bioxazolines (BiOX) are used as the chiral ligand. High-throughput experimentation significantly streamlined reaction development by identifying BiOX ligands for further investigation and by allowing for rapid optimization of conditions for new trifluoroborate salts.

Additional Information

Dr. Scott Virgil and the Caltech Center for Catalysis and Chemical Synthesis are gratefully acknowledged for access to analytical equipment. We thank Michael Takase for solving the structure of 5h and the Beckman Institute at Caltech and the Dow Next Generation Instrumentation Grant for support of the small molecule crystallography facility. Fellowship support was provided by the NSF (C.R.L., T.J.D., Grant No. DGE-1144469). S.E.R. acknowledges financial support from the NIH (R35GM118191). This work was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. We thank Nelo R. Rivera, Wildredo Pinto, and Yongqian Zhang for providing analytical support in obtaining optical rotation, HRMS, and FT-IR characterization data for 5j. We thank Benjamin Sherry, Jamie McCabe Dunn, Louis-Charles Campeau, and Kevin Campos (all employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA) for helpful discussions.

Files

nihms-1901575.pdf

Files (7.5 MB)

Name Size
md5:5d96f1beb891470f418f2f6a49ad7930
1.6 MB Preview Download
md5:208dfc6682c1f8160f6e6affd949c8d4
5.9 MB Preview Download

Additional details

Identifiers

Eprint ID
118940
Resolver ID
CaltechAUTHORS:20230125-514893900.20
PMCID
PMC10326726
DOI
10.1021/jacs.2c07917

Funding

Merck Sharp and Dohme
NSF Graduate Research Fellowship
DGE-1144469
NIH
R35GM118191-01
Caltech Beckman Institute
Dow Next Generation Educator Fund

Dates

Created
2023-02-22
Created from EPrint's datestamp field
Updated
2023-02-22
Created from EPrint's last_modified field