RESUMEN
A general intermolecular polarity-mismatched carboamination reaction of unactivated alkenes with unactivated alkyl halides has been developed. A series of nonactivated alkyl-substituted aziridines were constructed in exclusive regioselectivity. The dual polarity-mismatched mechanism might be involved.
RESUMEN
Cobalt complexes with chiral quinox ligands effectively promote the enantioselective conjugate addition of enones using aryl, heteroaryl, and alkenyl halides and sulfonates. Additionally, a cobalt complex with a strongly donating diphosphine, BenzP*, successfully catalyzes the asymmetric reductive arylation and alkenylation of α,ß-unsaturated amides. Both catalytic systems show broad scopes and tolerance of sensitive functional groups. Both reactions can be scaled up with low loadings of cobalt catalysts. Experimental results and density functional theory (DFT) calculations suggest a new mechanism of elementary 1,4-addition of aryl cobalt(I) complexes.
RESUMEN
The synthesis of deuterated gem-difluoroalkenes via selective deuterodefluorination of ß-CF3-cinnamates using a nickel catalyst has been reported for the first time. Commercially available deuterated formic acid is a cheap and convenient deuterium source. The nickel-catalyst showed high selectivity for monodefluorination and avoided competitive reactions such as multiple defluorination or hydrogenation.
RESUMEN
A nickel complex of chiral bisoxazolines catalyzed the stereoselective reductive arylation of ketones in high enantioselectivity. A range of common acyclic and cyclic ketones reacted without the aid of directing groups. Mechanistic studies using isolated complex of a chiral bis(oxazoline) (L)Ni(Ar)Br revealed that Mn reduction was not needed, while Lewis acidic titanium alkoxides were critical to ketone insertion.
RESUMEN
Cobalt complexes of chiral pyrox ligands catalyzed enantioselective reductive couplings of nonconjugated iododienes with aryl iodides or alkenyl bromides. The reaction enabled stereoselective syntheses of 5-7-membered azacycles carrying quaternary stereocenters. Mechanistically, cross-electrophile selectivity originated from selective coupling of alkylcobalt(I) complexes generated after cyclization with aryl iodides.
RESUMEN
Pd-catalyzed double Heck reaction allows regioselective 1,1-diarylation of unactivated aliphatic alkenes. When two different aryl bromides are used, the second aryl rings are added trans to aliphatic chains in the main olefinic isomers, consistent with a mechanism of two consecutive Heck arylations at the terminal carbons.
Asunto(s)
Alquenos , Estructura Molecular , Catálisis , Isomerismo , EstereoisomerismoRESUMEN
Nickel catalysts of chiral pyrox ligands promoted enantioselective reductive arylation and heteroarylation of aldimines, using directly (hetero)aryl halides and sulfonates. The catalytic arylation can also be conducted with crude aldimines generated from condensation of aldehydes and azaaryl amines. Mechanistically, density functional theory (DFT) calculations and experiments pointed to an elementary step of 1,4-addition of aryl nickel(I) complexes to N-azaaryl aldimines.
RESUMEN
A cobalt-catalyzed deuteration of amidoacrylates using deuterated methanol afforded α,ß-dideuterio-α-amino esters in excellent enantiomeric ratios (mostly >95 : 5) and almost complete deuteration (99 %). The new protocol was used to prepare dideuterio-α-amino acid fragments in some drugs. Furthermore, the stereoselective deuteration was applied in a concise synthesis of dideuterio l-DOPA.
RESUMEN
Catalytic enantioselective domino alkenylation-heteroarylation of nonconjugated iododienes proceeded with excellent stereoselectivity and broad scope of substrates. The reaction enables stereoselective syntheses of substituted azacycles such as piperidine, pyrrolidine azepine and dihydropyrans carrying new quaternary stereocenters. Mechanistically, C-H bonds of heterocycles were activated by lithium alkoxides via reversible deprotonation, rather than conventional palladium(ii)-assisted metalation processes. Many types of heteroarenes can be used, including not only azoles (such as thiazoles, oxazoles, imidazoles and oxadiazoles), but also nonazoles (thiophene, furan and azine N-oxides).
RESUMEN
A nickel complex of isoquinox promoted enantioselective conjugate arylation and heteroarylation of enones using aryl and heteroaryl halides directly. The reaction was successfully applied to stereoselective syntheses of ar-turmerone, chiral fragments of (+)-tolterodine and AZD5672. Mechanistically, experiments and calculations supported that an arylnickel(I) complex inserted to enones via an elementary 1,4-addition.
Asunto(s)
Níquel , Estereoisomerismo , Catálisis , Estructura MolecularRESUMEN
Pd-catalyzed chemo- and regiocontrollable 1,1-diarylation of unactivated aliphatic alkenes with two aryl halides was developed. Under the cationic reductive-delay Heck pathway, the first aryl insertion is followed by ß-H elimination, while the second aryl insertion is terminated by C-H bond formation.
Asunto(s)
Alquenos , Paladio , Alquenos/química , Catálisis , Estructura Molecular , Paladio/químicaRESUMEN
A nickel-catalyzed intermolecular arylcyanation of 8-aminoquinolinyl ß,γ-unsaturated amides is reported. The three-component reaction directly afforded diverse ß-cyano γ-aryl amides with exclusive chemo- and regioselectivity. The synthetic practicality of this approach is further demonstrated through multigram scale reaction, expanded transformations of the nitrile product, late-stage modification of complex molecules, and direct drug synthesis.
RESUMEN
This review summarizes the state-of-the-art in transition metal-catalyzed asymmetric alkylation of heteroarenes using alkenes (covering literature from 2000 to late 2021). Based on elementary reactions on metals for substrate activation, these reactions are broadly classified in several categories: (A) concerted oxidative addition of heteroaryl C-H bonds on rhodium(I) and iridium(I), (B) ligand-to-ligand hydrogen transfer (LLHT) on low-valent 3d metal complexes of nickel and cobalt, (C) different ways for deprotonation of heteroaryl C-H bonds by late transition metal complexes, especially palladium, including electrophilic aromatic substitution and a related mechanism, base-assisted intramolecular electrophilic substitution, concerted and nonconcerted metalation deprotonation, (D) σ-bond metathesis by d0 early transition metal complexes, (E) electrophilic activation of olefins by Pd(II), Pt(II) and Au(I), and (F) metal hydride insertion of aryl olefins and dienes. The demand to achieve enantiocontrol in the heteroarylation reactions has also driven innovation in chiral ancillary ligands, exemplified by extremely bulky, chiral N-heterocyclic carbenes for nickel catalysts, bulky monodentate oxazolines for Wacker-type reactions and chiral cyclopentadienyl ligands for half-sandwich complexes of scandium.
Asunto(s)
Alquenos , Paladio , Alquenos/química , Catálisis , Ligandos , Estructura Molecular , Paladio/químicaRESUMEN
We report a stereoselective conversion of terminal alkynes to α-chiral carboxylic acids using a nickel-catalyzed domino hydrocarboxylation-transfer hydrogenation reaction. A simple nickel/BenzP* catalyst displayed high activity in both steps of regioselective hydrocarboxylation of alkynes and subsequent asymmetric transfer hydrogenation. The reaction was successfully applied in enantioselective preparation of three nonsteroidal anti-inflammatory profens (>90 % ees) and the chiral fragment of AZD2716.
Asunto(s)
Alquinos/química , Ácidos Carboxílicos/síntesis química , Formiatos/química , Níquel/química , Ácidos Carboxílicos/química , Catálisis , Estructura Molecular , EstereoisomerismoRESUMEN
Nickel complexes ligated by strongly donating diphosphines catalyze enantioselective hydrogenation for the preparation of acyclic and cyclic ß-amido esters. A combination of acetic acid and indium powder provides protons and electrons to form nickel hydrido complexes under umpolung hydrogenation conditions.
RESUMEN
Palladium catalyzes a domino Heck arylation and alkylation of nonconjugated cyclodienes to produce trans isomers of disubstituted cyclohexenes in exceptionally high enantiomeric ratios, reaching 100:1 to 200:1 in many cases. Importantly, the interactions of the two CF bonds of Josiphos and the sodium ion of malonates facilitates stereoselective allylic attack through DFT calculations and experiments. This is a new type of attractive noncovalent interactions found in organometallic catalysis.
RESUMEN
Nickel-catalyzed Heck reaction of cycloalkenes delivers unusual conjugated arylated isomers. Nickel(0) catalysts ligated by chelating dialkylphosphines effectively activate not only aryl triflates as electrophiles, but also less reactive aryl mesylates, tosylates and pivalates. The omission of bases allows nickel hydride species to exist long enough to perform in situ olefin isomerization of initial Heck adducts.
RESUMEN
Asymmetric coupling proceeds efficiently between propargylic acetates, cycloalkenes and electron-rich heteroarenes including indoles, pyrroles, activated furans and thiophenes. 2,3-Disubstituted tetrahydrofurans and pyrrolidines are produced in trans configuration and excellent enantiomeric ratios. The reaction proceeds via Wacker-type attack of nucleophilic heteroarenes on alkenes activated by allenyl PdII species.
RESUMEN
Nickel-catalyzed intermolecular Heck reaction of cycloalkenes proceeds well with aryl triflates, mesylates and tosylates in excellent enantiomeric ratios. The asymmetric reductive Heck reaction also works with a 2-cyclopentenone ketal, which is equivalent to conjugate arylation of the enone itself.
RESUMEN
A simple catalyst of Ni(OAc)2 and P(t-Bu)3 enables selective C-alkylation of thioacetamides and primary acetamides with alcohols for the first time. Monoalkylation of thioamides, amides and t-butyl esters occurs in excellent yields (>95%). Mechanistic studies reveal that the reaction proceeds via a hydrogen autotransfer pathway.