[(DPEPhos)(bcp)Cu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst

Summary

Detailed and general protocols are presented for the synthesis of [(DPEPhos)(bcp)Cu]PF₆, a general copper-based photoredox catalyst, and for its use in synthetic chemistry for the direct arylation of C-H bonds in (hetero)arenes and radical cyclization of organic halides.

Abstract

Our group recently reported the use of [(DPEPhos)(bcp)Cu]PF₆ as a general copper-based photoredox catalyst which proved efficient to promote the activation of a broad variety of organic halides, including unactivated ones. These can then participate in various radical transformations such as reduction and cyclization reactions, as well as in the direct arylation of several (hetero)arenes. These transformations provide a straightforward access to a range of small molecules of interest in synthetic chemistry, as well as to biologically active natural products. Altogether, [(DPEPhos)(bcp)Cu]PF₆ acts as a convenient photoredox catalyst which appears to be an attractive, cheap and complementary alternative to the state-of-the-art iridium- and ruthenium-based photoredox catalysts. Here, we report a detailed protocol for the synthesis of [(DPEPhos)(bcp)Cu]PF₆, as well as NMR and spectroscopic characterizations, and we illustrate its use in synthetic chemistry for the direct arylation of (hetero)arenes and radical cyclization of organic halides. In particular, the direct arylation of N-methylpyrrole with 4-iodobenzonitrile to afford 4-(1-methyl-1H-pyrrol-2-yl)benzonitrile and the radical cyclization of N-benzoyl-N-[(2-iodoquinolin-3-yl)methyl]cyanamide to afford natural product luotonin A are detailed. The scope and limitations of this copper-based photoredox catalyst are also briefly discussed.

Introduction

Radical transformations have been known for decades to provide remarkably efficient pathways in synthetic chemistry which are often complementary to transformations based on cationic, anionic or pericyclic processes¹. While particularly promising for various types of transformations, radical-based chemistry has however long been underexploited, mainly because of the need for highly toxic reagents which considerably limits its attractiveness. Moreover, radical processes have long been considered as transformations associated with poor levels of control in terms of regio- and/or stereoselectivity, or leading to extensive dimerization and/or polym....

Protocol

1. Synthesis of [(DPEPhos)(bcp)Cu]PF₆

1. Add 3.73 g (10.00 mmol) of tetrakisacetonitrile copper(I) hexafluorophosphate and 5.39 g (10.00 mmol) of DPEPhos to a 2 L round bottom flask equipped with a magnetic stir bar.
2. Fit the round bottom flask with a three neck vacuum adapter connected to a vacuum line and an argon line.
3. Evacuate the flask under vacuum and backfill with argon three times. Replace the three neck vacuum adapter by a rubber septum.
   NOTE: The reaction can be performed under air with slightly reduced efficiency (see discussion section for details).
4. Add 800 mL of dry dichloromethane.
   NOTE: Dich....

Results

Synthesis of [(DPEPhos)(bcp)Cu]PF₆
As shown by the protocol described in the above section, the synthesis of [(DPEPhos)(bcp)Cu]PF₆ is particularly convenient and can be easily performed on a multigram scale. The ¹H and ¹³C NMR spectra indicate formation of the pure complex (Figure 4A,B). The spectroscopic data correspond to those previously reported³¹.

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Discussion

Synthesis of [(DPEPhos)(bcp)Cu]PF₆
The synthesis of [(DPEPhos)(bcp)Cu]PF₆ is typically performed using dry dichloromethane (distilled prior to use) and under argon to ensure the highest yield, purity and good reproducibility. As mentioned in the protocol, the synthesis of [(DPEPhos)(bcp)Cu]PF₆ can be performed with regular dichloromethane (99.8%) and/or under air with variable efficiencies. Indeed, while the use of regular dichloromethane under argon afforded the sa.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Material
Bathocuproine (bcp)	Acros	161340010
Acetonitrile, 99.9+	Acros	326811000
Celite 545	Acros	349670025
Bis[(2-diphenylphosphino)phenyl] ether (DPEphos)	Acros	383370050
Calcium hydride	Acros	C/1620/48
Dichloromethane, 99.8%	Fisher Chemical	D/1852/25
Dietyl ether, >= 99%	Fisher Chemical	D/2400/MS21
Ethyl acetate	Fisher Chemical	E/0900/25
N-Methylpyrrole, 99%	Sigma Aldrich	M78801
4-Iodobenzonitrile, 98%	Combi-Blocks	OR-3151
Petroleum ether (40-60 °)	Fisher Chemical	P/1760/25
Potassium carbonate, anhydrous	Fisher Chemical	P/4120/60
Tetrakisacetonitrile copper(I) hexafluorophosphate, 97%	Sigma Aldrich	346276
Equipment
1H and 13C NMR spectrometer	Bruker	Avance 300 Spectrometer
1H and 13C NMR spectrometer	Varian	VNMRS 400 Spectrometer
420 nm light tubes	Luzchem	LZC-420
Blue LEDs lamp	Kessil	H150-Blue
Blue LEDs strips	Eglo	92065
Photochemistry Device PhotoRedOx Box	Hepatochem	HCK1006-01-016
Photoreactor	Luzchem	CCP-4V
Spectrofluorimeter	Shimadzu	RF-5301PC
UV/Vis spectrometer	Perkin Elmer	Lambda 40