Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Investigating the nature of palladium chain-walking in the enantioselective redox-relay Heck reaction of alkenyl alcohols.

ABSTRACT: The mechanism of the redox-relay Heck reaction was investigated using deuterium-labeled substrates. Results support a pathway through a low energy palladium-alkyl intermediate that immediately precedes product formation, ruling out a tautomerization mechanism. DFT calculations of the relevant transition structures at the M06/LAN2DZ+f/6-31+G* level of theory show that the former pathway is favored by 5.8 kcal/mol. Palladium chain-walking toward the alcohol, following successive ?-hydride eliminations and migratory insertions, is also supported in this study. The stereochemistry of deuterium labels is determined, lending support that the catalyst remains bound to the substrate during the relay process and that both cis- and trans-alkenes form from ?-hydride elimination.

SUBMITTER: Hilton MJ

PROVIDER: S-EPMC4275159 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Investigating the nature of palladium chain-walking in the enantioselective redox-relay Heck reaction of alkenyl alcohols.

Hilton Margaret J MJ Xu Li-Ping LP Norrby Per-Ola PO Wu Yun-Dong YD Wiest Olaf O Sigman Matthew S MS

The Journal of organic chemistry 20140910 24

The mechanism of the redox-relay Heck reaction was investigated using deuterium-labeled substrates. Results support a pathway through a low energy palladium-alkyl intermediate that immediately precedes product formation, ruling out a tautomerization mechanism. DFT calculations of the relevant transition structures at the M06/LAN2DZ+f/6-31+G* level of theory show that the former pathway is favored by 5.8 kcal/mol. Palladium chain-walking toward the alcohol, following successive β-hydride eliminat ...[more]

PMID: 25186804

Similar Datasets

Enantioselective Heck arylations of acyclic alkenyl alcohols using a redox-relay strategy.

Project description:Progress in the development of asymmetric Heck couplings of arenes and acyclic olefins has been limited by a tenuous understanding of the factors that dictate selectivity in migratory insertion and ?-hydride elimination. On the basis of key mechanistic insight recently garnered in the exploration of selective Heck reactions, we report here an enantioselective variant that delivers ?-, ?-, or ?-aryl carbonyl products from acyclic alkenol substrates. The catalyst system imparts notable regioselectivity during migratory insertion and promotes the migration of the alkene's unsaturation toward the alcohol to ultimately form the ketone product. The reaction uses aryldiazonium salts as the arene source, yields enantiomeric products from opposite starting alkene configurations, and uses a readily accessible ligand. The racemic nature of the alkenol substrate does not bias the enantioselection.

| S-EPMC3583361 | biostudies-literature

Relative reactivity of alkenyl alcohols in the palladium-catalyzed redox-relay Heck reaction.

Project description:The relative rates of alkenyl alcohols in the Pd-catalyzed redox-relay Heck reaction were measured in order to examine the effect of their steric and electronic properties on the rate-determining step. Competition experiments between an allylic alkenyl alcohol and two substrates with differing chain lengths revealed that the allylic alcohol reacts 3-4 times faster in either case. Competition between di- and trisubstituted alkenyl alcohols provided an interesting scenario, in which the disubstituted alkene was consumed first followed by reaction of the trisubstituted alkene. Consistent with this observation, the transition structures for the migratory insertion of the aryl group into the di- and trisubstituted alkenes were calculated with a lower barrier for the former. An internal competition between a substrate containing two alcohols with differing chain lengths demonstrated the catalyst's preference for migrating towards the closest alcohol. Additionally, it was observed that increasing the electron density in the arene boronic acid promotes a faster reaction, which correlates with Hammett ?p values to give a ? of -0.87.

| S-EPMC4573459 | biostudies-literature

Enantioselective redox-relay oxidative heck arylations of acyclic alkenyl alcohols using boronic acids.

Project description:A general, highly selective asymmetric redox-relay oxidative Heck reaction using achiral or racemic acyclic alkenols and boronic acid derivatives is reported. This reaction delivers remotely functionalized arylated carbonyl products from acyclic alkenol substrates, with excellent enantioselectivity under mild conditions, bearing a range of useful functionality. A preliminary mechanistic investigation suggests that the regioselectivity of the initial migratory insertion is highly dependent on the electronic nature of the boronic acid and more subtle electronic effects of the alkenyl alcohol.

| S-EPMC3698857 | biostudies-literature

Palladium-Catalyzed Enantioselective Redox-Relay Heck Arylation of 1,1-Disubstituted Homoallylic Alcohols.

Project description:An enantioselective redox-relay oxidative Heck arylation of 1,1-disubstituted alkenes to construct β-stereocenters was developed using a new pyridyl-oxazoline ligand. Various 1,2-diaryl carbonyl compounds were readily obtained in moderate yield and good to excellent enantioselectivity. Additionally, analysis of the reaction outcomes using multidimensional correlations revealed that enantioselectivity is tied to specific electronic features of the 1,1-disubstituted alkenol and the extent of polarizability of the ligand.

| S-EPMC5039009 | biostudies-literature

Mechanism, reactivity, and selectivity in palladium-catalyzed redox-relay Heck arylations of alkenyl alcohols.

Project description:The enantioselective Pd-catalyzed redox-relay Heck arylation of acyclic alkenyl alcohols allows access to various useful chiral building blocks from simple olefinic substrates. Mechanistically, after the initial migratory insertion, a succession of ?-hydride elimination and migratory insertion steps yields a saturated carbonyl product instead of the more general Heck product, an unsaturated alcohol. Here, we investigate the reaction mechanism, including the relay function, yielding the final carbonyl group transformation. M06 calculations predict a ??G(‡) of 1 kcal/mol for the site selectivity and 2.5 kcal/mol for the enantioselectivity, in quantitative agreement with experimental results. The site selectivity is controlled by a remote electronic effect, where the developing polarization of the alkene in the migratory insertion transition state is stabilized by the C-O dipole of the alcohol moiety. The enantioselectivity is controlled by steric repulsion between the oxazoline substituent and the alcohol-bearing alkene substituent. The relay efficiency is due to an unusually smooth potential energy surface without high barriers, where the hydroxyalkyl-palladium species acts as a thermodynamic sink, driving the reaction toward the carbonyl product. Computational predictions of the relative reactivity and selectivity of the double bond isomers are validated experimentally.

| S-EPMC3985895 | biostudies-literature

Alkenyl carbonyl derivatives in enantioselective redox relay Heck reactions: accessing ?,?-unsaturated systems.

Project description:A highly enantioselective and site-selective Pd-catalyzed arylation of alkenes linked to carbonyl derivatives to yield ?,?-unsaturated systems is reported. The high site selectivity is attributed to both a solvent effect and the polarized nature of the carbonyl group, both of which have been analyzed through multidimensional analysis tools. The reaction can be performed in an iterative fashion allowing for a diastereoselective installation of two aryl groups along an alkyl chain.

| S-EPMC4785797 | biostudies-literature

Palladium-catalyzed enantioselective Heck alkenylation of acyclic alkenols using a redox-relay strategy.

Project description:We report a highly enantioselective intermolecular Heck reaction of alkenyl triflates and acyclic primary or racemic secondary alkenols. The mild reaction conditions permit installation of a wide range of alkenyl groups at positions ?, ?, or ? to a carbonyl group in high enantioselectivity. The success of this reaction is attributed to the use of electron-withdrawing alkenyl triflates, which offer selective ?-hydride elimination followed by migration of the catalyst through the alkyl chain to give the alkenylated carbonyl products. The synthetic utility of the process is demonstrated by a two-step modification of a reaction product to yield a tricyclic core structure, present in various natural products.

| S-EPMC4785804 | biostudies-literature

Palladium-Catalyzed Enantioselective Redox-Relay Heck Alkynylation of Alkenols To Access Propargylic Stereocenters.

Project description:An enantioselective redox-relay Heck alkynylation of di- and trisubstituted alkenols to construct propargylic stereocenters is disclosed using a new pyridine oxazoline ligand. This strategy allows direct access to chiral ?-alkynyl carbonyl compounds employing allylic alcohol substrates in contrast to more traditional conjugate addition methods.

| S-EPMC5528850 | biostudies-literature

Palladium-Catalyzed Enantioselective Relay Heck Arylation of Enelactams: Accessing ?,?-Unsaturated ?-Lactams.

Project description:In this Communication, we describe the construction of chiral ?,?-unsaturated ?-lactams, widely used as pharmacophores, in high yields and excellent enantioselectivities using an oxidative relay Heck arylation reaction. This strategy also allows facile access to 7-substituted ?,?-unsaturated ?-lactam products and ?-lactams containing a tetrasubstituted nitrogen-bearing stereocenter.

| S-EPMC5993423 | biostudies-other

Palladium-Catalyzed Enantioselective Heck Alkenylation of Trisubstituted Allylic Alkenols: A Redox-Relay Strategy to Construct Vicinal Stereocenters.

Project description:An enantioselective, redox-relay Heck alkenylation of trisubstituted allylic alkenol substrates has been developed. This process enables the construction of vicinal stereocenters in high diastereo- and enantioselectivity and allows the formation of enolizable α-carbonyl methyl-substituted stereocenters with no observed epimerization under the reported reaction conditions.

| S-EPMC5395252 | 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