Chemoselective Cross-coupling Research Articles

Flux-Screened Copper/Electric Dual-Catalyzed Chemo- and Enantioselective Ullmann-Type C-C Coupling Reactions.

This study introduces an innovative copper/electric dual-catalyzed approach to Ullmann coupling reactions. Our research delineates a series of chemoselective cross-couplings among various halogenated aromatics and enantioselective couplings involving halogenated aryl aldehydes. We employed a flux screening technique to refine the reaction parameters, which is rarely reported in the field of electrochemical synthesis. This advancement accelerates the determination of optimal reaction conditions and affords some inspiration for developing sustainable and ecofriendly chemical synthesis.

Enantioselective Arylation of Sulfenamides to Access Sulfilimines Enabled by Palladium Catalysis

AbstractSulfur‐containing functional groups have garnered considerable attention due to their common occurrence in ligands, pharmaceuticals, and insecticides. Nevertheless, enantioselective synthesis of sulfilimines, particularly diaryl sulfilimines remains a challenging and persistent goal. Herein we report a highly enantio‐ and chemoselective cross–coupling of sulfenamides with aryl diazonium salt to construct diverse S(IV) stereocenters by Pd catalysis. Bisphosphine ligands bearing sulfinamide groups play a crucial role in achieving high reactivity and selectivity. This approach provides a general, modular and divergent framework for quickly synthesizing chiral sulfilimines and sulfoximines that are otherwise challenging to access. In addition, the origins of the high chemoselectivity and enantioselectivity were extensively investigated using density functional theory calculations.

Enantioselective Arylation of Sulfenamides to Access Sulfilimines Enabled by Palladium Catalysis.

Sulfur-containing functional groups have garnered considerable attention due to their common occurrence in ligands, pharmaceuticals, and insecticides. Nevertheless, enantioselective synthesis of sulfilimines, particularly diaryl sulfilimines remains a challenging and persistent goal. Herein we report a highly enantio- and chemoselective cross-coupling of sulfenamides with aryl diazonium salt to construct diverse S(IV) stereocenters by Pd catalysis. Bisphosphine ligands bearing sulfinamide groups play a crucial role in achieving high reactivity and selectivity. This approach provides a general, modular and divergent framework for quickly synthesizing chiral sulfilimines and sulfoximines that are otherwise challenging to access. In addition, the origins of the high chemoselectivity and enantioselectivity were extensively investigated using density functional theory calculations.

SciPROP-R: An Effective Bisphosphine Ligand for the Chemo-Selective Iron-Catalyzed Suzuki–Miyaura Coupling of Alkyl Chlorides

Abstract Novel 2-substituted 1,3-bis[bis(3′,5′-di-tert-butylphenyl)phosphino]propanes (SciPROP-R; 1-R), as well as their iron complexes FeCl2(SciPROP-R) 2-R, are synthesized. Single-crystal X-ray analysis and solution-phase Fe K- and L-edge XAS of 2-R reveals that these complexes maintain tetrahedral geometry and hence paramagnetic high-spin properties both in the solid state and in the solution phase. 31P NMR results demonstrate that the superior coordination ability of SciPROP-TB (1-TB) is due to the bulky tert-butyl group at position 2 of the propane-1,3-diyl linker of the ligand. These novel iron-complexes catalyze Suzuki–Miyaura-type cross coupling under mild conditions. Notably, iron(II) chloride–1-TB complex (2-TB) exhibits excellent catalytic activity owing to the high coordination ability and electron-donating nature of 1-TB, being effective for chemoselective cross coupling between various alkyl chlorides and arylboron compounds.

Pd-Catalyzed Organometallic-Free Homologation of Arylboronic Acids Enabled by Chemoselective Transmetalation.

A Pd-catalyzed homologation of arylboronic acids is reported. Halomethylboronic acid pinacol esters (Bpin) undergo a remarkably facile, yet rare, oxidative addition enabled by an α-boryl effect. Simultaneous chemoselective transmetalation allows use of these metalloid reagents for formal C1 insertion to deliver benzyl Bpin products without the requirement for stoichiometric organometallic reagents. The utility of the process is demonstrated by stepwise C(sp3)-C(sp2) cross-coupling of the boronic ester products into diarylmethane pharmacophores and electrophile/nucleophile chemoselective cross-coupling. Control experiments that demonstrate the reactivity enhancement provided by the α-boryl effect are provided, along with a description of the limitations of the formal homologation process.

Platinum–P(BFPy)3-catalyzed regioselective diboration of terminal alkynes with (pin)B–B(aam)

An electron-deficient triarylphosphine-coordinated Pt-catalyzed diboration of terminal alkynes with (pin)B–B(aam) provides vic-diborylalkenes, whose difference in the boron-Lewis acidities allows chemoselective cross-coupling to proceed sequentially.

Rapid Access to Diverse Potassium Acyltrifluoroborates (KATs) through Late-Stage Chemoselective Cross-Coupling Reactions.

Potassium acyltrifluoroborates (KATs) are opening up new avenues in chemical biology, materials science, and synthetic organic chemistry due to their intriguing reactivities. However, the synthesis of these compounds remains mostly complicated and time-consuming. Herein, we have developed chemoselective Pd-catalyzed approaches for the late-stage diversification of arenes bearing prefunctionalized KATs. These approaches feature chemoselective cross-coupling, rapid diversification, functional group tolerance, mild reaction conditions, simple operation, and high yields.

Suzuki-Miyaura Cross-Coupling of Esters by Selective O-C(O) Cleavage Mediated by Air- and Moisture-Stable [Pd(NHC)(μ-Cl)Cl]2 Precatalysts: Catalyst Evaluation and Mechanism.

The cross-coupling of aryl esters has emerged as a powerful platform for the functionalization of otherwise inert acyl C-O bonds in chemical synthesis and catalysis. Herein, we report a combined experimental and computational study on the acyl Suzuki-Miyaura cross-coupling of aryl esters mediated by well-defined, air- and moisture-stable Pd(II)-NHC precatalysts [Pd(NHC)(μ-Cl)Cl]2. We present a comprehensive evaluation of [Pd(NHC)(μ-Cl)Cl]2 precatalysts and compare them with the present state-of-the-art [(Pd(NHC)allyl] precatalysts bearing allyl-type throw-away ligands. Most importantly, the study reveals [Pd(NHC)(μ-Cl)Cl]2 as the most reactive precatalysts discovered to date in this reactivity manifold. The unique synthetic utility of this unconventional O-C(O) cross-coupling is highlighted in the late-stage functionalization of pharmaceuticals and sequential chemoselective cross-coupling, providing access to valuable ketone products by a catalytic mechanism involving Pd insertion into the aryl ester bond. Furthermore, we present a comprehensive study of the catalytic cycle by DFT methods. Considering the clear advantages of [Pd(NHC)(μ-Cl)Cl]2 precatalysts on several levels, including facile one-pot synthesis, superior atom-economic profile to all other Pd(II)-NHC catalysts, and versatile reactivity, these should be considered as the 'first-choice' catalysts for all routine applications in ester O-C(O) bond activation.

A Synthetic Approach to Dimetalated Arenes Using Flow Microreactors and the Switchable Application to Chemoselective Cross-Coupling Reactions.

In spite of their potential utility, the chemistry of dimetalated arenes is still in its infancy because they are extremely difficult to synthesize. We report a novel method of synthesizing arenes bearing a boryl group and a metallic substituent, such as boryl, silyl, stannyl, or zincyl groups, in an integrated flow microreactor based on the generation and reactions of aryllithiums bearing a trialkyl borate moiety. The bimetallic arenes showed a remarkable chemoselectivity in palladium-catalyzed cross-coupling reactions. The selectivity was switched by the selection of the metal species that constitutes the dimetalated arenes as well as appropriate catalysts.

Chemoselective Cross-Coupling Reactions on Pyridine Derivatives

Key words transition metals - cross-coupling - oligopyridines - Mcl-1 inhibitors

Concise, gram-scale synthesis of furo[2,3-b]pyridines with functional handles for chemoselective cross-coupling

A concise 4-step synthesis of furo[2,3-b]pyridines, with handles in the 3- and 5-positions for palladium mediated cross-coupling reactions, is described. The synthetic route has been optimized, with only one step requiring purification by column chromatography. The route is amenable to scale-up, and was successfully executed on a multi-gram scale. Furopyridines are of growing interest in medicinal chemistry, and this route should enable easy access to the core for structure-activity relationship (SAR) studies.

Chemoselective Cross-Coupling between Two Different and Unactivated C(aryl)-O Bonds Enabled by Chromium Catalysis.

We report here the first example of cross-coupling between two different and unactivated C(aryl)-O bonds with chromium catalysis. The combination of a low-cost Cr(II) salt, 4,4'-di-tert-butyl-2,2'-dipyridyl (dtbpy) as the ligand, and magnesium as the reductant shows high reactivity in promoting the reductive cross-coupling of aryl methyl ether derivatives with aryl esters by cleavage and coupling of two different C(aryl)-O bonds under mild conditions. The formation of active low-valent Cr species by reduction of CrCl2 with Mg can be considered, which prefers to initially activate the C(aryl)-O bond of phenyl methyl ether with the chelation help of dtbpy and an o-imine auxiliary. The subsequent consecutive reduction, second C(aryl)-O activation, and reductive elimination allow for the achievement of selective cross-coupling of C(aryl)-O/C(aryl)-O bonds.

Chromium Catalyzed Reductive Chemoselective Cross-Coupling between Anisole Derivatives and Aryl Ester

Chromium Catalyzed Reductive Chemoselective Cross-Coupling between Anisole Derivatives and Aryl Ester

Base-Controlled One-Pot Chemoselective Suzuki–Miyaura Reactions for the Synthesis of Unsymmetrical Terphenyls

We report a chemoselective Suzuki–Miyaura reaction protocol of using bromophenyl fluorosulfonate as building block for the preparation of unsymmetrical terphenyls. The chemoselective cross-coupling of bromophenyl fluorosulfonate and arylboronic acids can be achieved by controlling base species without using any ligands. Under this methodology, various of m- and p-unsymmetrical terphenyls were obtained in moderate to good yields.

Mixed Diboration of Alkynes Catalyzed by LiOH: Regio- and Stereoselective Synthesis of cis-1,2-Diborylalkenes

A diboration of terminal alkynes with an unsymmetrical diboron reagent pinBBdan has been achieved using LiOH as the catalyst in the presence of stoichiometric amounts of MeOH, affording 1,2-diborylalkenes with different boryl groups. The reaction proceeds in a highly regio- and stereoselective manner through cis-addition of pinBBdan to the C-C triple bond, with the Bdan moiety being incorporated at the internal position. By taking advantage of the different reactivities of the two boryl groups, the mixed diboration product can undergo the sequential, chemoselective cross-couplings with aryl bromides to form trisubstituted alkenes.

Chemoselective Cross-Coupling of Secondary Phosphine Chalcogenides with Aminophenols: Synthesis of Aminophenylchalcogenophosphinic Acids O-Esters

Chemoselective reaction of secondary phosphine chalcogenides with 2-aminophenol under mild conditions (room temperature, 2–4 h, CCl4–Et3N) led to the formation of aminophenylchalcogenophosphinic acids O-esters in a yield of up to 80%.

Chemoselective Catalytic Dehydrogenative Cross-Coupling of 2-Acylimidazoles: Mechanistic Investigations and Synthetic Scope

Chemoselective iron-catalyzed dehydrogenative cross-coupling using 2-acylimidazoles is described. The addition of a phosphine oxide ligand substantially facilitated the generation of tert-butoxy radicals from di-tert-butyl peroxide, allowing for efficient benzylic C–H bond cleavage under mild conditions. Extensive mechanistic studies revealed that the enolization of 2-acylimidazole proceeded through dual iron catalyst activation, followed by subsequent chemoselective cross-coupling with a benzyl radical over an undesired benzyl radical-derived homocoupling dimer that inevitably formed in earlier reported conditions. A variety of alkylarenes, aliphatic alkane, and functionalized 2-acylimidazoles were applicable, demonstrating the synthetic utility of the present catalysis. Contiguous all-carbon quaternary carbons were constructed through dehydrogenative cross-coupling. The catalytic chemoselective activation of 2-acylimidazole over bidentate coordinative and much more acidic malonate diester was particular noteworthy. Catalytic oxidative cross-enolate coupling of two distinct carboxylic acid equivalents was also achieved using acetonitrile as a coupling partner.

Chemoselective Suzuki-Miyaura Cross-Coupling via Kinetic Transmetallation.

Chemoselective Suzuki-Miyaura cross-coupling generally requires a designed deactivation of one nucleophile towards transmetallation. Here we show that boronic acids can be chemoselectively reacted in the presence of ostensibly equivalently reactive boronic acid pinacol (BPin) esters by kinetic discrimination during transmetallation. Simultaneous electrophile control allows sequential chemoselective cross-couplings in a single operation in the absence of protecting groups.

ChemInform Abstract: Nickel‐Catalyzed Reductive Cross‐Coupling of Benzyl Chlorides with Aryl Chlorides/Fluorides: A One‐Pot Synthesis of Diarylmethanes.

The first nickel-catalyzed, magnesium-mediated reductive cross-coupling between benzyl chlorides and aryl chlorides or fluorides is reported. A variety of diarylmethanes can be prepared in good to excellent yields in a one-pot manner using easy-to-access mixed PPh3/NHC Ni(II) complexes of Ni(PPh3)(NHC)Br2 (NHC = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, IPr, 1a; 1,3-di-tert-butylimidazol-2-ylidene, ItBu, 1b) as catalyst precursors. Activation of polychloroarenes or chemoselective cross-coupling based on the difference in catalytic activity between 1a and 1b is used to construct oligo-diarylmethane motifs.

Nickel-Catalyzed Reductive Cross-Coupling of Benzyl Chlorides with Aryl Chlorides/Fluorides: A One-Pot Synthesis of Diarylmethanes.

The first nickel-catalyzed, magnesium-mediated reductive cross-coupling between benzyl chlorides and aryl chlorides or fluorides is reported. A variety of diarylmethanes can be prepared in good to excellent yields in a one-pot manner using easy-to-access mixed PPh3/NHC Ni(II) complexes of Ni(PPh3)(NHC)Br2 (NHC = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, IPr, 1a; 1,3-di-tert-butylimidazol-2-ylidene, ItBu, 1b) as catalyst precursors. Activation of polychloroarenes or chemoselective cross-coupling based on the difference in catalytic activity between 1a and 1b is used to construct oligo-diarylmethane motifs.