Nickel-catalyzed reductive cross-coupling of polyfluoroarenes with alkyl electrophiles by site-selective C–F bond activation

A nickel-catalyzed reductive cross-coupling reactions between polyfluoroarenes and alkyl electrophiles is reported to access substituted fluoroarenes through chelation-assisted C–F activation. Diverse primary and secondary alkyl (pseudo)halides can be employed to couple with polyfluoroarenes, showing excellent regioselectivity. Furthermore, the nickel-catalyzed asymmetric cross-coupling of polyfluoroarenes with racemic alkyl halides is preliminarily explored. In addition, the practicability of the title transformation is also demonstrated by total synthesis of losmapimod and an analog as key steps. The developed method exhibits many advantages, including economic catalytic systems, commercially available alkyl electrophiles, and lack of sensitive organometallic reagents.     

Catalytic borylation of o-xylene and heteroarenes via C–H activation

Iridium and rhodium complexes catalyze the borylation of xylene and different heteroarenes using pinacolborane via C–H activation. Various five-membered heterocycles such as thiophene, pyrrole, thionaphthene, and indole derivatives yield the borylated products in moderate to good yields. In general, the reactions proceed with high selectivity to give borylation ortho to the heteroatom.     

A greener catalyst for hydroboration of imines—external electric field modify the reaction mechanism

Usually, an extra catalyst (for example, the transition metal complexes) need to be used in catalyzing hydroboration, which involved the cost, environment, and so forth. Here, a greener and controllable catalyst—external electric field (EEF) was used to study its effect on hydroboration of N-(4-methylbenzyl)aniline (PhN═CHPhMe) with pinacolboane (HBPin). The results demonstrated that EEF could affect the barrier heights of both two pathways of this reaction. More significantly, flipping the direction of EEF could modify the reaction mechanism to induce a dominant inverse hydroboration at some field strength. That is to say, oriented EEF is a controlling switch for the anti- or Markovnikov hydroboration reaction of imines. This investigation is meaningful for the exploration of greener catalyst for chemistry reaction and guide a new method for the Markovnikov hydroboration addition. © 2019 Wiley Periodicals, Inc.     

Electrochemical oxidation of allylic CH bond for α, β-unsaturated ketones without peroxide

α,β-Unsaturated ketone is one of the important building blocks of the plenty of alkaloids, spices and pharmaceutical agents. Herein, we describe a peroxide-free electrochemical strategy to realize site-selective allylic C − H oxidation for the synthesis of α,β-unsaturated ketones. This electrochemically driven oxidation exhibits a broad substrate scope. Mechanistic investigations of this reaction uncovered HOAc and H₂O as the oxygen source to achieve peroxide-free electrochemical allylic C − H oxidation.     

Manganese-catalyzed bicyclic annulations of imines and α,β-unsaturated esters via C-H activation

A manganese-catalyzed bicyclic annulation of imines with α,β-unsaturated esters via C–H activation is described, which provides an expedient access to fused β-lactams in one-step operation with high efficiency and good functional group tolerance. Of note, both ketimines and aldimines are amenable to this transformation. Mechanistic studies have identified a five-membered azamanganacycle as the key reaction intermediate.     

Nickel-catalyzed asymmetric α-arylation and heteroarylation of ketones with chloroarenes: effect of halide on selectivity, oxidation state, and room-temperature reactions

We report the α-arylation of ketones with a range of aryl chlorides with enantioselectivities from 90 to 99% ee catalyzed by the combination of Ni(COD)(2) and (R)-BINAP and the coupling of ketones with a range of heteroaryl chlorides with enantioselectivities up to 99% ee catalyzed by Ni(COD)(2) and (R)-DIFLUORPHOS. The analogous reactions of bromoarenes occur with much lower enantioselectivities. Mechanistic studies showed that the difference in the rates of decomposition of the arylnickel(II) halide intermediates to {[(R)-BINAP]NiX}(2) likely accounts for the difference in the enantioselectivities of the reactions of bromoarenes and chloroarenes. This catalyst decomposition can be overcome by conducting the reactions with [(R)-BINAP]Ni(η(2)-NC-Ph) (4), which undergoes oxidative addition to haloarenes at room temperature.     

Rational design of iron catalysts for C–X bond activation

We have quantum chemically studied the iron-mediated C X bond activation (X = H, Cl, CH₃) by d⁸-FeL₄ complexes using relativistic density functional theory at ZORA-OPBE/TZ2P. We find that by either modulating the electronic effects of a generic iron-catalyst by a set of ligands, that is, CO, BF, PH₃, BN(CH₃)₂, or by manipulating structural effects through the introduction of bidentate ligands, that is, PH₂(CH₂)_nPH₂ with n = 6–1, one can significantly decrease the reaction barrier for the C X bond activation. The combination of both tuning handles causes a decrease of the C H activation barrier from 10.4 to 4.6 kcal mol⁻¹. Our activation strain and Kohn-Sham molecular orbital analyses reveal that the electronic tuning works via optimizing the catalyst–substrate interaction by introducing a strong second backdonation interaction (i.e., “ligand-assisted” interaction), while the mechanism for structural tuning is mainly caused by the reduction of the required activation strain because of the pre-distortion of the catalyst. In all, we present design principles for iron-based catalysts that mimic the favorable behavior of their well-known palladium analogs in the bond-activation step of cross-coupling reactions.     

New electrophilic addition of α-diazoesters with ketones for enantioselective C-N bond formation

α-Diazoesters were discovered to be good electrophiles in a catalytic asymmetric α-functionalization of ketones for the first time. This reaction also provided a direct and efficient method for C-N bond formation with excellent yields (up to 98%) and enantioselectivities (up to 99% ee) under mild conditions. The application of the electrophilicity of α-diazoesters opens up a novel way to access the diversity of diazo chemistry.     

N,N-Dimethylphosphoramidic dichloride: a convenient reagent for the preparation of β-lactams from acetic acids and imines

A convenient reagent for the preparation of β-lactams from acetic acids and imines is described. A new route to α-keto-β-lactams from 3-bis(ethylthio)β-lactams is also reported. Reaction of 4-acethyl-β-lactams with diazomethane is also made.     

Transition-metal-free site-selective C–F bond activation for synthesis of 8-aminoquinolines

An efficient and general selective method for the synthesis of 8-aminoquinoline derivatives has been disclosed through transition metal direct C–N coupling from fluoroquinolines and arylamines. Significantly, good chemo- and regio-selectivity was observed for polyfluoroquinolines in which only C–F bond on 8-substituted position was broken. Thus, this methodology proves its value as an inexpensive and efficient synthetic way to access quinolin-8amine derivatives in moderate to good yields.     

TFA-catalyzed C–N bond activation of enamides with indoles: efficient synthesis of 3,3-bisindolylpropanoates and other bisindolylalkanes

An efficient TFA-catalyzed cleavage of C–N bonds in alkylation of indoles by tertiary enamides was described. A variety of bisindolylalkane derivatives, especially 3,3-bisindolylpropanoates, were expeditiously synthesized in good yields.     

Asymmetric hydroboration and Matteson homologation for the preparation of fluorinated α-phenethanols

The asymmetric catalytic hydroboration-oxidation of ring-fluorinated styrenes (F-PhCHCH₂) was achieved with catecholborane along with a combination of [Rh(COD)₂]⁺BF₄⁻ and (R)-BINAP providing 81-96% enantioselectivities for the product alcohols for ortho-unhindered styrenes. A deleterious effect of a 2,6-disubstitution on the enantioselectivity of the product alcohol was observed. 2-Trifluoromethylstyrene also provides only 53% ee, probably due to the steric bulk of the CF₃ group at the ortho-position of styrene. Asymmetric homologation of fluorophenylmetals (magnesium bromide or lithium) with pinanediol α-chloroethylboronate, followed by oxidation readily furnished the desired 1-(2,6-difluorophenyl)- and 1-(perfluorophenyl)ethanols in 94-95% ee.     

Nickel-catalyzed cross-coupling of phenols and arylboronic acids through an in situ phenol activation mediated by PyBroP

A new method for the Suzuki–Miyaura cross‐coupling of phenols and arylboronic acids through in situ phenol activation mediated by PyBroP is presented. The reaction proceeds efficiently by using cost‐effective, markedly stable [NiCl₂(dppp)] (dppp=1,3‐bis(diphenylphosphino)propane) as the catalyst in only 5 mol % loading, as well as in the absence of extra ligands. The method exhibits broad applicability and high efficiency towards a wide range of both phenols and boronic acids, including activated, nonactivated, deactivated, and heteroaromatic coupling partners. In addition, various functional groups, such as ether, amino, cyano, ester, and ketone groups, are compatible with this transformation. Notably, arylboronic acids containing an unprotected NH₂ group and 2‐heterocyclic boronic acids, which are generally problematic for coupling under conventional conditions, are also viable substrates, although moderate yields were obtained for sterically hindered substrates. Consequently, the in situ cross‐coupling methodology coupled with the use of an inexpensive and stable nickel catalyst provides a rapid and efficient pathway for the assembly of biaryls and heterobiaryls with structural diversity from readily available phenol compounds.     

Base-promoted diastereoselective addition of nitromethane and nitroethane to N-tert-butylsulfinyl imines: synthesis of N-protected α-amino acids and amino ketones

The reaction of N-tert-butylsulfinyl imines with nitromethane or nitroethane in the presence of NaHCO₃ under solvent-free reaction conditions gave β-nitro amine derivatives with reasonable levels of diastereoselectivity. Enantioenriched N-tert-butylsulfinyl protected α-amino acids or α-amino ketones are accessible upon oxidation of the adducts derived from nitromethane or nitroethane, respectively.     

Improved and expanded one-pot,two-component Boulton-Katritzky syntheses of N–N bond containing bicyclic heterocycles

Improved and expanded one-pot, two-component syntheses of bicyclic heterocycles containing a 3-N-acyl-3-amino-1,2-pyrazole motif from N′-hydroxy-carboxyamidines and acylbenzotriazoles have been developed. Importantly, this sequence obviates the need for hydrazine or N-aminating reagents to synthesize the key nitrogen–nitrogen (N–N) bond of these heterocycles, which is formed via Boulton-Katritzky rearrangement. A diverse array of pharmaceutically relevant N–N containing heterocycles has been prepared with this methodology using readily available reagents without the need for special equipment or conditions.     

Intramolecular hydrogen bond energy and cooperative interactions in α-, β-, and γ-cyclodextrin conformers

Accurate estimation of individual intramolecular hydrogen bond (H-bond) energies is an intricate task for multiply H-bonded systems. In such cases, the hydrogen bond strengths could be highly influenced by the cooperative interactions, for example, those between hydroxyl groups in sugars. In this work, we use the recently proposed molecular tailoring approach-based quantification (Deshmukh, Gadre, and Bartolotti, J Phys Chem A 2006, 110, 12519) to the extended systems of cyclodextrins (CDs). Further, the structure and stability of different conformers of α-, β-, and γ-CDs are explained based on the energetics and cooperative contribution to the strength of these H-bonds. The estimated O-H···O H-bond energies in the various CD conformers are found to vary widely from 1.1 to 8.3 kcal mol(-1). The calculated energy contributions to cooperativity toward the H-bond strengths fall in the range of 0.25-2.75 kcal mol(-1).