Cobalt-Catalyzed Cross-Coupling Research Articles

Cobalt-catalyzed cross-coupling of nitrogen-containing heterocyclic phosphonium salts with arylmagnesium reagents

Cobalt-catalyzed cross-couplings of nitrogen-containing heterocyclic phosphonium salts with arylmagnesium halides proceeded efficiently with the aid of cobalt(II) catalyst and copper(I) salt in tetrahydrofuran at ambient temperature, producing the desired 4-arylated pyridine, quinoline, and quinoxaline in modest to good yields.

Cobalt-catalyzed cross-coupling of Umpolung carbonyls with alkyl halides under mild conditions.

While classical cross-couplings are dominated by palladium and nickel catalysts, cobalt-based catalysts have shown unique advantages for such cross-coupling reactions in terms of higher catalytic activity and lower toxicity. Herein, we describe a novel cobalt-catalyzed alkyl-alkyl cross-coupling reaction of hydrazone with alkyl halides under mild reaction conditions, where the use of a PNP-type pincer ligand is essential for catalysis. Both aldehyde and ketone hydrazones are compatible with this reaction, giving a series of C(sp3)-C(sp3) coupling products in moderate to good yields.

Cobalt‐Catalyzed α‐Arylation of Substituted α‐Bromo α‐Fluoro β‐Lactams with Diaryl Zinc Reagents: Generalization to Functionalized Bromo Derivatives

A cobalt-catalyzed cross-coupling of α-bromo α-fluoro β-lactams with diarylzinc or diallylzinc reagents is herein disclosed. The protocol proved to be general, chemoselective and operationally simple allowing the C4 functionalization of β-lactams. The substrate scope was expanded to α-bromo lactams and amides, α-bromo lactones and esters as well as N- and O-containing heterocycles.

Synthesis of Chiral α-Fluorinated Diarylmethanes by Asymmetric Cobalt-Catalyzed Cross-Coupling

Synthesis of Chiral α-Fluorinated Diarylmethanes by Asymmetric Cobalt-Catalyzed Cross-Coupling

Cobalt-Catalyzed Cross-Couplings between Alkyl Halides and Grignard Reagents.

Metal-catalyzed cross-couplings have emerged as essential tools for the construction of C-C bonds. The identification of efficient catalytic systems as well as large substrate scope made these cross-couplings key reactions to access valuable molecules ranging from materials, agrochemicals to active pharmaceutical ingredients. They have been increasingly integrated in retrosynthetic plans, allowing shorter and original route development. Palladium-catalyzed cross-couplings still largely rule the field, with the most popular reactions in industrial processes being the Suzuki and Sonogashira couplings. However, the extensive use of palladium complexes raises several problems such as limited resources, high cost, environmental impact, and frequent need for sophisticated ligands. As a consequence, the use of nonprecious and cheap metal catalysts has appeared as a new horizon in cross-coupling development. Over the last three decades, a growing interest has thus been devoted to Fe-, Co-, Cu-, or Ni-catalyzed cross-couplings. Their natural abundance makes them cost-effective, allowing the conception of more sustainable and less expensive chemical processes, especially for large-scale production of active molecules. In addition to these economical and environmental considerations, the 3d metal catalysts also exhibit complementary reactivity with palladium complexes, facilitating the use of alkyl halide partners due to the decrease of β-elimination side reactions. In particular, by using cobalt catalysts, numerous cross-couplings between alkyl halides and organometallics have been described. However, cobalt catalysis still stays far behind palladium catalysis in terms of popularity and applications, and the expansion of the substrate scope as well as the development of simple and robust catalytic systems remains an important challenge.In 2012, our group entered the cobalt catalysis field by developing a cobalt-catalyzed cross-coupling between C-bromo glycosides and Grignard reagents. The generality of the coupling allowed the preparation of a range of valuable C-aryl and C-vinyl glycoside building blocks. We then focused on the functionalization of saturated N-heterocycles, and a variety of halo-azetidines, -pyrrolidines, and -piperidines were successfully reacted with aryl and alkenyl Grignard reagents under cobalt catalysis. With the objective of preparing valuable α-aryl amides, a cobalt-catalyzed cross-coupling applied to α-bromo amides was studied and then extended to α-bromo lactams. Recently, we also reported an efficient and general cross-coupling involving cyclopropyl- and cyclobutyl-magnesium bromides. This method allows the alkylation of functionalized small strained rings by a range of primary and secondary alkyl halides.

Stereoselective Cobalt-Catalyzed Cross-Coupling Reactions of Arylzinc Chlorides with α-Bromolactones and Related Derivatives.

α-Bromolactones bearing a substituent in the β-position undergo a highly trans-diastereoselective arylation with arylzinc chlorides in the presence of 10-20% CoCl2 and 10-20% PPh3 in THF under mild conditions (25 °C, 16 h) leading to optically enriched α-arylated lactones and protected aldol products (99% ee) in 52-96% yield. The synthetic utility of this arylation was demonstrated by the stereoselective preparation of an artificial rotenoid MOM-protected munduserol derivative.

Cobalt Catalyzed C-P Bond Formation by Cross-Coupling of Boronic Acids with P(O)H Compounds in Presence of Zinc.

In our current work, we have reported the first cobalt-catalyzed cross-coupling of arylboronic acid with alkyl/aryl phosphites under mild conditions. The reaction was carried out in the presence of zinc powder as an additive and ter-pyridine as a ligand. The use of non-precious cobalt salt makes the protocol advantageous, as it is inexpensive and more abundant than the previously used methods where precious metal salts (Pd and Pt) were used. The reaction has a wide substrate scope and the products were obtained in good yields.

Cobalt-Catalyzed Olefinic C-H Alkenylation/Alkylation Switched by Carbonyl Groups.

The first cobalt-catalyzed cross-couplings between olefins has been demonstrated to provide C(alkenyl)-H alkenylation and alkylation products, using complex [Cp*Co(CO)I2]. While coupling partner acrylates afforded conjugated dienoates, α,β-unsaturated ketones led to γ-alkenyl ketones completely, representing a switchable C-H functionalization controlled by different carbonyl groups.

Cobalt-Catalyzed Cross-Coupling Reactions of Aryl Triflates and Lithium Arylborates.

A catalyst system comprising CoCl2/IAd·HBF4 enables the Suzuki-Miyaura cross-coupling reaction of a broad range of aryl triflates and arylboronic esters that are activated by n-butyllithium.

Introduction of Cyclopropyl and Cyclobutyl Ring on Alkyl Iodides through Cobalt-Catalyzed Cross-Coupling.

A cobalt-catalyzed cross-coupling between alkyl iodides and cyclopropyl, cyclobutyl, and alkenyl Grignard reagents is disclosed. The reaction allows the introduction of strained rings on a large panel of primary and secondary alkyl iodides. The catalytic system is simple and nonexpensive, and the reaction is general, chemoselective, and diastereoconvergent. The alkene resulting from the cross-coupling can be transformed to substituted cyclopropanes using a Simmons-Smith reaction. The formation of radical intermediates during the coupling is hypothesized.

Cobalt-catalyzed cross-coupling of lithium (hetero)aryl zincates with heteroaryl chlorides and bromides

A mild, efficient and practical Co-catalyzed cross coupling reaction of a variety of activated heteroaryl chlorides and bromides with lithium aryl zincates that were in situ generated from lithium aryl boronates with ZnBr2 was described.

Preparation of Polyfunctional Naphthyridines by Cobalt-Catalyzed Cross-Couplings of Halogenated Naphthyridines with Magnesium and Zinc Organometallics.

CoCl2 (5%) catalyzes cross-couplings of various halogenated naphthyridines with alkyl- and arylmagnesium halides. Also, arylzinc halides undergo smooth cross-couplings with various naphthyridines in the presence of CoCl2·2LiCl (5%) and sodium formate (50%), leading to polyfunctional arylated naphthyridines. Two of these arylated naphthyridines are highly fluorescent, with quantum efficiencies reaching 95% and long excited-state lifetimes of up to 12 ns.

Cobalt-Catalyzed Cross-Coupling of α-Bromo Amides with Grignard Reagents.

A cobalt-catalyzed cross-coupling between α-bromo amides and Grignard reagents is disclosed. The reaction is general and allows access to a large variety of α-aryl and β,γ-unsaturated amides. Some mechanistic investigations have been undertaken to determine the nature of the intermediate species.

Cobalt-Catalyzed Cross-Coupling of Alkyl Fluorides

Cobalt-Catalyzed Cross-Coupling of Alkyl Fluorides

Cobalt-Catalyzed Cross-Couplings of Bench-Stable Alkynylzinc Pivalates with (Hetero)Aryl and Alkenyl Halides.

A catalytic system consisting of CoCl2·2LiCl and TMEDA enables the cross-coupling of various electron-poor aryl and heteroaryl halides with various alkynylzinc pivalates. Coupling with alkenyl halides proceeds with retention of configuration.

Large-Scale Cobalt-Catalyzed Cross-Couplings of Functionalized Bench-Stable Arylzinc Pivalates with (Hetero)Aryl and Alkenyl Halides­

A robust and scalable CoCl2-catalyzed cross-coupling between functionalized arylzinc pivalates and various electron-poor (hetero)aryl and alkenyl halides is reported.

A Robust and Broadly Applicable Cobalt‐Catalyzed Cross‐Coupling of Functionalized Bench‐Stable Organozinc Pivalates with Unsaturated Halides

AbstractWe report a robust and broadly applicable CoCl2‐catalyzed cross‐coupling between functionalized aryl and heteroaryl zinc pivalates and various electron‐poor aryl and heteroaryl halides (X=Cl, Br, I). Couplings with (E)‐ or (Z)‐bromo‐ or iodo‐alkenes proceed with retention of configuration. Also, alkynyl bromides react with arylzinc pivalates providing arylated alkynes.

Cobalt-Catalyzed C(sp2)-C(sp3) Cross-Coupling Reactions of Diarylmanganese Reagents with Secondary Alkyl Iodides.

A cobalt-catalyzed cross-coupling of diarylmanganese reagents with secondary alkyl iodides using the THF-soluble salt CoCl2·2LiCl, which leads to the cross-coupling products in up to 92% yield, is reported. High diastereoselectivities can be reached in these cross-couplings (dr up to 99:1). Remarkably, rearrangement of secondary alkyl iodides to unbranched products was not observed in these C-C forming reactions.

Cobalt-Catalyzed Cross-Coupling Route to Homoallylic Alcohols and Amines

Cobalt-Catalyzed Cross-Coupling Route to Homoallylic Alcohols and Amines

A practical cobalt-catalyzed cross-coupling of benzylic zinc reagents with aryl and heteroaryl bromides or chlorides.

A catalytic system consisting of 5 mol% CoCl2 and 10 mol% isoquinoline allows a convenient cross-coupling of benzylic zinc reagents with various aryl and heteroaryl bromides or chlorides leading to polyfunctionalized diaryl- and aryl-heteroaryl-methane derivatives.