Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nickel/bis(oxazoline)-catalyzed asymmetric Negishi arylations of racemic secondary benzylic electrophiles to generate enantioenriched 1,1-diarylalkanes.

ABSTRACT: A tertiary stereogenic center that bears two different aryl substituents is found in a variety of bioactive compounds, including medicines such as Zoloft and Detrol. We have developed an efficient method for the synthesis of enantioenriched 1,1-diarylalkanes from readily available racemic benzylic alcohols. Formation of a benzylic mesylate (which is not isolated), followed by treatment with an arylzinc reagent, LiI, and a chiral nickel/bis(oxazoline) catalyst, furnishes the Negishi cross-coupling product in high ee and good yield. A wide array of functional groups (e.g., an aryl iodide, a thiophene, and an N-Boc-indole) are compatible with the mild reaction conditions. This method has been applied to a gram-scale synthesis of a precursor to Zoloft.

SUBMITTER: Do HQ

PROVIDER: S-EPMC3869004 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Nickel/bis(oxazoline)-catalyzed asymmetric Negishi arylations of racemic secondary benzylic electrophiles to generate enantioenriched 1,1-diarylalkanes.

Do Hien-Quang HQ Chandrashekar E R R ER Fu Gregory C GC

Journal of the American Chemical Society 20131028 44

A tertiary stereogenic center that bears two different aryl substituents is found in a variety of bioactive compounds, including medicines such as Zoloft and Detrol. We have developed an efficient method for the synthesis of enantioenriched 1,1-diarylalkanes from readily available racemic benzylic alcohols. Formation of a benzylic mesylate (which is not isolated), followed by treatment with an arylzinc reagent, LiI, and a chiral nickel/bis(oxazoline) catalyst, furnishes the Negishi cross-couplin ...[more]

PMID: 24164502

Similar Datasets

Stereoconvergent Negishi Arylations of Racemic Secondary Alkyl Electrophiles: Differentiating between a CF3 and an Alkyl Group.

Project description:In this report, we establish that a readily available nickel/bis(oxazoline) catalyst accomplishes a wide array of enantioconvergent cross-couplings of arylzinc reagents with CF3-substituted racemic secondary alkyl halides, a process that necessitates that the chiral catalyst be able to effectively distinguish between a CF3 and an alkyl group in order to provide good ee. We further demonstrate that this method can be applied without modification to the catalytic asymmetric synthesis of other families of fluorinated organic compounds.

| S-EPMC4610818 | biostudies-other

Nickel-Catalyzed Enantioconvergent Borylation of Racemic Secondary Benzylic Electrophiles.

Project description:Nickel-catalyzed cross-coupling has emerged as the most versatile approach to date for achieving enantioconvergent carbon-carbon bond formation using racemic alkyl halides as electrophiles. In contrast, there have not yet been reports of the application of chiral nickel catalysts to the corresponding reactions with heteroatom nucleophiles to produce carbon-heteroatom bonds with good enantioselectivity. Herein, we establish that a chiral nickel/pybox catalyst can borylate racemic secondary benzylic chlorides to provide enantioenriched benzylic boronic esters, a highly useful family of compounds in organic synthesis. The method displays good functional group compatibility (e.g., being unimpeded by the presence of an indole, a ketone, a tertiary amine, or an unactivated alkyl bromide), and both of the catalyst components (NiCl2 ?glyme and the pybox ligand) are commercially available.

| S-EPMC6200647 | biostudies-literature

Catalytic enantioselective cross-couplings of secondary alkyl electrophiles with secondary alkylmetal nucleophiles: Negishi reactions of racemic benzylic bromides with achiral alkylzinc reagents.

Project description:We have developed a nickel-catalyzed method for the asymmetric cross-coupling of secondary electrophiles with secondary nucleophiles, specifically, stereoconvergent Negishi reactions of racemic benzylic bromides with achiral cycloalkylzinc reagents. In contrast to most previous studies of enantioselective Negishi cross-couplings, tridentate pybox ligands are ineffective in this process; however, a new, readily available bidentate isoquinoline-oxazoline ligand furnishes excellent ee's and good yields. The use of acyclic alkylzinc reagents as coupling partners led to the discovery of a highly unusual isomerization that generates a significant quantity of a branched cross-coupling product from an unbranched nucleophile.

| S-EPMC3474870 | biostudies-literature

Catalytic asymmetric synthesis of secondary nitriles via stereoconvergent Negishi arylations and alkenylations of racemic ?-bromonitriles.

Project description:The first method for the stereoconvergent cross-coupling of racemic ?-halonitriles is described, specifically, nickel-catalyzed Negishi arylations and alkenylations that furnish an array of enantioenriched ?-arylnitriles and allylic nitriles, respectively. Noteworthy features of this investigation include: the highly enantioselective synthesis of ?-alkyl-?-aryl nitriles that bear secondary ?-alkyl substituents; the first examples of the use of alkenylzinc reagents in stereoconvergent Negishi reactions of alkyl electrophiles; demonstration of the utility of a new family of ligands for asymmetric Negishi cross-couplings (a bidentate bis(oxazoline), rather than a tridentate pybox); in the case of arylzinc reagents, carbon-carbon bond formation at a remarkably low temperature (-78 °C), the lowest reported to date for an enantioselective cross-coupling of an alkyl electrophile; a mechanistic dichotomy between Negishi reactions of an unactivated versus an activated secondary alkyl bromide.

| S-EPMC3415582 | biostudies-literature

Asymmetric Suzuki cross-couplings of activated secondary alkyl electrophiles: arylations of racemic alpha-chloroamides.

Project description:A nickel-catalyzed stereoconvergent method for the enantioselective Suzuki arylation of racemic alpha-chloroamides has been developed. This process provides a unique example of an asymmetric arylation of an alpha-haloamide, an enantioselective arylation of an alpha-chlorocarbonyl compound, and an asymmetric Suzuki reaction with an activated alkyl electrophile or an arylboron reagent. The method is also applicable to the corresponding enantioselective cross-coupling of alpha-bromoamides. The coupling products can be transformed without racemization into enantioenriched alpha-arylcarboxylic acids and primary alcohols. A modest kinetic resolution of the alpha-chloroamide was observed; a mechanistic study indicated that the selectivity may reflect discrimination by the chiral catalyst of the two enantiomeric alpha-chloroamides in an irreversible oxidative-addition process.

| S-EPMC2924160 | biostudies-literature

Nickel/bis(oxazoline)-catalyzed asymmetric Kumada reactions of alkyl electrophiles: cross-couplings of racemic alpha-bromoketones.

Project description:The first asymmetric Kumada reactions of alkyl electrophiles are described, specifically, cross-couplings of racemic alpha-bromoketones with aryl Grignard reagents. Several features of this investigation are of interest. First, the couplings proceed at remarkably low temperature (-40 or -60 degrees C), which enables the asymmetric synthesis of racemization-prone alpha-arylketones. Second, dialkyl ketones undergo enantioselective coupling in good ee and yield. Third, readily available bis(oxazolines) are shown for the first time to be effective ligands for cross-couplings of alkyl electrophiles, thereby opening the door to new opportunities in asymmetric catalysis.

| S-EPMC2814537 | biostudies-literature

Enantioconvergent cross-couplings of racemic alkylmetal reagents with unactivated secondary alkyl electrophiles: catalytic asymmetric Negishi ?-alkylations of N-Boc-pyrrolidine.

Project description:Although enantioconvergent alkyl-alkyl couplings of racemic electrophiles have been developed, there have been no reports of the corresponding reactions of racemic nucleophiles. Herein we describe Negishi cross-couplings of racemic ?-zincated N-Boc-pyrrolidine with unactivated secondary halides, thus providing a one-pot, catalytic asymmetric method for the synthesis of a range of 2-alkylpyrrolidines (an important family of target molecules) from N-Boc-pyrrolidine, a commercially available precursor. Preliminary mechanistic studies indicated that two of the most straightforward mechanisms for enantioconvergence (dynamic kinetic resolution of the organometallic coupling partner and a simple ?-hydride elimination/?-migratory insertion pathway) are unlikely to be operative.

| S-EPMC3803154 | biostudies-literature

Nickel-catalyzed Negishi arylations of propargylic bromides: a mechanistic investigation.

Project description:Although nickel-catalyzed stereoconvergent couplings of racemic alkyl electrophiles are emerging as a powerful tool in organic chemistry, to date there have been no systematic mechanistic studies of such processes. Herein, we examine the pathway for enantioselective Negishi arylations of secondary propargylic bromides, and we provide evidence for an unanticipated radical chain pathway wherein oxidative addition of the C-Br bond occurs through a bimetallic mechanism. In particular, we have crystallographically characterized a diamagnetic arylnickel(II) complex, [(i-Pr-pybox)Ni(II)Ph]BAr(F)4, and furnished support for [(i-Pr-pybox)Ni(II)Ph](+) being the predominant nickel-containing species formed under the catalyzed conditions as well as a key player in the cross-coupling mechanism. On the other hand, our observations do not require a role for an organonickel(I) intermediate (e.g., (i-Pr-pybox)Ni(I)Ph), which has previously been suggested to be an intermediate in nickel-catalyzed cross-couplings, oxidatively adding alkyl electrophiles through a monometallic pathway.

| S-EPMC4277758 | biostudies-literature

Nickel-Catalyzed Borylation of Benzylic Ammonium Salts: Stereospecific Synthesis of Enantioenriched Benzylic Boronates.

Project description:We have developed a stereospecific, nickel-catalyzed cross-coupling of secondary benzylic ammonium salts and diboronate esters to deliver highly enantioenriched benzylic boronates. This reaction utilizes amine-derived electrophiles, which are readily available in high enantiopurity, and simple, inexpensive nickel catalysts. This reaction has broad scope, enabling synthesis of a variety of secondary benzylic boronates in good yields and excellent ee's.

| S-EPMC4809423 | biostudies-literature

Nickel-Catalyzed Asymmetric Reductive Cross-Coupling To Access 1,1-Diarylalkanes.

Project description:An asymmetric Ni-catalyzed reductive cross-coupling of (hetero)aryl iodides and benzylic chlorides has been developed to prepare enantioenriched 1,1-diarylalkanes. As part of these studies, a new chiral bioxazoline ligand, 4-heptyl-BiOX (L1), was developed in order to obtain products in synthetically useful yield and enantioselectivity. The reaction tolerates a variety of heterocyclic coupling partners, including pyridines, pyrimidines, indoles, and piperidines.

| S-EPMC5851002 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data