The first example of the oxidative addition of a C(sp3)–F bond in trifluoromethylarenes to a nickel(0) complex is described. A nickel(0) complex that bears two N-heterocyclic carbene (NHC) ligands ...of low steric demand is able to cleave C(sp3)–F bonds of trifluoromethylarenes to afford the corresponding trans-difluorobenzyl nickel(II) fluoride complexes. Isolation and characterization studies suggested that the cleavage of the C(sp3)–F bond proceeds via an η2-arene nickel(0) complex. Taking advantage of the reactivity of these nickel(II) fluoride complexes, we developed a catalytic hydrodefluorination of trifluoromethylarenes using hydrosilanes. A computational study indicated that the electron-rich nickel(0) center supported by two relatively small NHC ligands cleaves the C(sp3)–F bond via a syn-SN2′ mechanism.
Recent progress on the triarylborane (BAr3)-catalyzed reductive N-alkylation of amines is briefly summarized in this Perspective. The highlighted examples are divided into two main classes, that is, ...the B(C6F5)3-catalyzed hydroamination of alkynes and subsequent catalytic hydrogenation, as well as the BAr3-catalyzed reductive N-alkylation of carbonyl compounds such as aldehydes, ketones, and carboxylic acids in the presence of hydrosilanes or molecular hydrogen. Key aspects on several catalytic systems are emphasized in order to discuss the reaction mechanisms, substrate scope, and practical applications for the preparation of medicinal compounds, as well as the identification of remaining challenges in this area.
Tricyclic furan derivatives with multiple chiral centers are ubiquitous in natural products. Construction of such tricyclic scaffolds in a stereocontrolled, step-economic, and atom-economic manner is ...a key challenge. Here we show a nickel-catalyzed highly enantioselective synthesis of hydronaphtho1,8-bcfurans with five contiguous chiral centers via desymmetrization of alkynyl-cyclohexadienone by oxidative cyclization and following formal 4 + 2 cycloaddition processes. Alkynyl-cyclohexadienone was synthesized in one step from easily accessible phenols. This reaction represents excellent chemo-selectivity, regio-selectivity, diastereo-selectivity, and enantio-selectivity (single diastereomer, up to 99% ee). An extraordinary regioselectivity in the formal 4 + 2 cycloaddition step with enones revealed the diverse reactivity of the nickelacycle intermediate. Desymmetrization of alkynyl-cyclohexadienones via oxidative cyclization on nickel was supported by the isolation of a nickelacycle from a stoichiometric reaction. Enantioenriched tricyclic products contain various functional groups such as C=O and C=C. The synthetic utility of these products was demonstrated by derivatization of these functional groups.Tricyclic furanic compounds with multiple chiral centers are found in a variety of natural products. Here, the authors show a highly enantioselective nickel-catalyzed procedure to access tricyclic oxygen-containing scaffolds with five contiguous chiral centers.
This report describes the first Pd0‐catalyzed cross‐coupling of hexafluorobenzene (C6F6) with diarylzinc compounds to give a variety of pentafluorophenyl arenes. This reaction could be applied to ...other perfluoroarenes, such as octafluorotoluene, pentafluoropyridine, and perfluoronaphthalene, to give the corresponding polyfluorinated coupling products. The optimal ligand in this catalytic reaction was PCy3, and lithium iodide was indispensable as an additive for the coupling reaction. One of the roles of lithium iodide in this catalytic reaction was to promote the oxidative addition of one CF bond of C6F6 to palladium. Stoichiometric reactions revealed that an expected oxidative‐addition product, trans‐Pd(C6F5)I(PCy3)2, generated from the reaction of Pd(PCy3)2 with C6F6 in the presence of lithium iodide, was not involved in the catalytic cycle. Instead, a transient three‐coordinate, monophosphine‐ligated species, Pd(C6F5)I(PCy3), emerged as a potential intermediate in the catalytic cycle. Therefore, we isolated a novel PdII complex, Pd(C6F5)I(PCy3)(py), in which pyridine (py) acted as a labile ligand to generate the transient species. In fact, in the presence of lithium iodide, this PdII complex was found to react smoothly with diphenylzinc to give the desired pentafluorophenyl benzene, whereas the same reaction conducted in the absence of lithium iodide resulted in a decreased yield of pentafluorophenyl benzene, which indicated that the other role of lithium iodide was to enhance the reactivity of the organozinc species during the transmetalation step.
Transforming CF into CC: Pd0/PCy3‐catalyzed cross‐coupling of C6F6 with a variety of diarylzinc compounds proceeds in the presence of lithium iodide to give pentafluorobiaryl compounds in good‐to‐excellent yields (see scheme). The key intermediate in this catalytic reaction is a transient, three‐coordinated, monophosphine‐ligated species, Pd(C6F5)I(PCy3), which was generated by oxidative addition of the CF bond of C6F6 to Pd(PCy3)2, followed by dissociation of a PCy3 ligand.
A highly enantioselective synthesis of 3-aryl-, vinyl-, and alkynyl-2,1-benzoxasiloles (up to 99.9% ee and 99% yield) was achieved via the sequential activation of an aldehyde and a silane by ...nickel(0). This strategy was applied to a simultaneous generation of carbon- and silicon-stereogenic centers with excellent selectivity (dr = 99:1) via diastereotopic aryl transfer. Initial mechanistic studies revealed the complete switching of an aryl-transfer process from an intermolecular (racemic synthesis in the presence of IPr) to an intramolecular (enantioselective synthesis using chiral NHC, L5) fashion. A plausible rationale for the switching of the aryl-transfer process is given by a preliminary DFT calculation, which suggests that the coordination of 1 to the nickel(0)/L5 fragment in an η2-arene:η2-aldehyde fashion would be a key to the intramolecular process, while the formation of the corresponding intermediate is not possible in the presence of IPr. Owing to the chemically labile nature of its C–Si and O–Si bonds, enantioenriched benzoxasiloles are utilized for the synthesis of chiral building blocks and antihistaminic and anticholinergic drug molecules such as (R)-orphenadrine and (S)-neobenodine with no erosion of the enantiomeric excess.
A new strategy for C–C bond formation with organoboronates through C–F activation of fluorinated alkenes and arenes was developed. In this Pd‐catalyzed Suzuki–Miyaura‐type cross‐coupling reaction, ...neither a base for enhancing the reactivity of the organoboron reagents nor a Lewis acid for promoting C–F bond activation was required. A fluoropalladium intermediate played an essential role in this reaction. In addition, a Ni(NHC) catalyst was efficient for C–C coupling through C–F bond activation of fluoroarenes.
Pd0/PR3 complexes promote C–C bond formation with organoboronates through C–F bond activation of fluorinated alkenes. Mechanistic studies show that a PdII fluoride intermediate plays an essential role in this base‐free cross‐coupling reaction. Moreover, a Ni(NHC) catalyst is efficient for C–C coupling through C–F bond cleavage of fluoroarenes.
In the presence of a catalytic amount of Ni(cod)2 (cod = 1,5-cyclooctadiene) and PCy3 (Cy = cyclohexyl), the cross-tetramerization of tetrafluoroethylene (TFE), alkynes, and ethylene occurred in a ...highly selective manner to afford a variety of 1,3-dienes with a 3,3,4,4-tetrafluorobutyl chain. In addition, a Ni(0)-catalyzed cross-tetramerization of TFE, alkynes, ethylene, and styrenes was developed. These catalytic reactions might proceed via partially fluorinated five- and seven-membered nickelacycle key intermediates.
In the presence of a catalytic amount of Ni(cod)2 and IPr (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), a cross-trimerization reaction of tetrafluoroethylene (TFE), ethylene, and ...aldehydes proceeded in a selective manner to afford a variety of 4,4,5,5-tetrafluoro-1-pentanone derivatives in good to excellent yields. The present system involves a five-membered nickelacycle key intermediate generated via the oxidative cyclization of TFE and ethylene.
Abstract
Cheminformatics-based machine learning (ML) has been employed to determine optimal reaction conditions, including catalyst structures, in the field of synthetic chemistry. However, such ...ML-focused strategies have remained largely unexplored in the context of catalytic molecular transformations using Lewis-acidic main-group elements, probably due to the absence of a candidate library and effective guidelines (parameters) for the prediction of the activity of main-group elements. Here, the construction of a triarylborane library and its application to an ML-assisted approach for the catalytic reductive alkylation of aniline-derived amino acids and C-terminal-protected peptides with aldehydes and H
2
is reported. A combined theoretical and experimental approach identified the optimal borane, i.e., B(2,3,5,6-Cl
4
-C
6
H)(2,6-F
2
-3,5-(CF
3
)
2
-C
6
H)
2
, which exhibits remarkable functional-group compatibility toward aniline derivatives in the presence of 4-methyltetrahydropyran. The present catalytic system generates H
2
O as the sole byproduct.
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