Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enantioselective synthesis of dialkylated N-heterocycles by palladium-catalyzed allylic alkylation.

ABSTRACT: The enantioselective synthesis of ?-disubstituted N-heterocyclic carbonyl compounds has been accomplished using palladium-catalyzed allylic alkylation. These catalytic conditions enable access to various heterocycles, such as morpholinone, thiomorpholinone, oxazolidin-4-one, 1,2-oxazepan-3-one, 1,3-oxazinan-4-one, and structurally related lactams, all bearing fully substituted ?-positions. Broad functional group tolerance was explored at the ?-position in the morpholinone series. We demonstrate the utility of this method by performing various transformations on our useful products to readily access a number of enantioenriched compounds.

SUBMITTER: Numajiri Y

PROVIDER: S-EPMC6410707 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Enantioselective synthesis of dialkylated N-heterocycles by palladium-catalyzed allylic alkylation.

Numajiri Yoshitaka Y Jiménez-Osés Gonzalo G Wang Bo B Houk K N KN Stoltz Brian M BM

Organic letters 20150225 5

The enantioselective synthesis of α-disubstituted N-heterocyclic carbonyl compounds has been accomplished using palladium-catalyzed allylic alkylation. These catalytic conditions enable access to various heterocycles, such as morpholinone, thiomorpholinone, oxazolidin-4-one, 1,2-oxazepan-3-one, 1,3-oxazinan-4-one, and structurally related lactams, all bearing fully substituted α-positions. Broad functional group tolerance was explored at the α-position in the morpholinone series. We demonstrate ...[more]

PMID: 25714704

Similar Datasets

Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones.

Project description:The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF3)3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee's up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee.

| S-EPMC4640231 | biostudies-literature

Enantioselective synthesis of α-quaternary Mannich adducts by palladium-catalyzed allylic alkylation: total synthesis of (+)-sibirinine.

Project description:A catalytic enantioselective method for the synthesis of α-quaternary Mannich-type products is reported. The two-step sequence of (1) Mannich reaction followed by (2) decarboxylative enantioselective allylic alkylation serves as a novel strategy to in effect access asymmetric Mannich-type products of "thermodynamic" enolates of substrates possessing additional enolizable positions and acidic protons. Palladium-catalyzed decarboxylative allylic alkylation enables the enantioselective synthesis of five-, six-, and seven-membered ketone, lactam, and other heterocyclic systems. The mild reaction conditions are notable given the acidic free N-H groups and high functional group tolerance in each of the substrates. The utility of this method is highlighted in the first total synthesis of (+)-sibirinine.

| S-EPMC4311947 | biostudies-literature

Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams.

Project description:The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures.

| S-EPMC3266627 | biostudies-literature

Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Protected Benzoin-Derived Enol Carbonates.

Project description:The enantioselective palladium-catalyzed decarboxylative allylic alkylation of fully substituted α-hydroxy acyclic enol carbonates providing tetrasubstituted benzoin derivatives is reported. Investigation into the transformation revealed that preparation of the starting material as a single enolate isomer is crucial for optimal enantioselectivity. The obtained alkylation products contain multiple reactive sites that can be utilized toward the synthesis of stereochemically rich derivatives. COMMUNICATION.

| S-EPMC7942817 | biostudies-literature

Palladium(II)-catalyzed enantioselective synthesis of 2-vinyl oxygen heterocycles.

Project description:2-Vinylchromanes (1), 2-vinyl-1,4-benzodioxanes (2), and 2,3-dihydro-2-vinyl-2H-1,4-benzoxazines (3) can be prepared in high yields (90-98%) and excellent enantiomeric purities (87-98% ee) by [COP-OAc](2)-catalyzed cyclization of phenolic (E)-allylic trichloroacetimidate precursors. Deuterium-labeling and computational experiments are consistent with these cyclization reactions taking place by an anti-oxypalladation/syn-deoxypalladation mechanism. 2-Vinylchromanes can also be prepared in good yields and high enantiomeric purities from analogous (E)-allylic acetate precursors, which constitutes the first report that acetate is a competent leaving group in COP-catalyzed enantioselective S(N)2' substitution reactions.

| S-EPMC3296363 | biostudies-literature

Catalytic Enantioselective Synthesis of Acyclic Quaternary Centers: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully Substituted Acyclic Enol Carbonates.

Project description:The first enantioselective palladium-catalyzed decarboxylative allylic alkylation of fully substituted acyclic enol carbonates providing linear α-quaternary ketones is reported. Investigation into the reaction revealed that the use of an electron-deficient phosphinooxazoline ligand renders the enolate geometry of the starting material inconsequential, with the same enantiomer of product obtained in the same level of selectivity regardless of the starting ratio of enolates. As a result, a general method toward acyclic all-carbon quaternary stereocenters has been developed.

| S-EPMC6103296 | biostudies-literature

Ligand controlled highly regio- and enantioselective synthesis of alpha-acyloxyketones by palladium-catalyzed allylic alkylation of 1,2-enediol carbonates.

Project description:The palladium catalyzed decarboxylative asymmetric allylic alkylation of allyl 1,2-enediol carbonates 1 can decompose to either alpha-hydroxyketones 3 or alpha-hydroxyaldehydes 4. The product distribution is largely controlled by the ligand. Using Lnaph in DME we exclusively obtained the ketone product in good to excellent yields and high enantiomeric excesses. The reaction proceeds under extremely mild conditions, so we can have a broad range of choices of OR. Besides the commonly used protection groups such as OAc and OPiv, a more functionalized group such as methyl but-2-enoyl group can also be used, downstream process of which can afford other synthetically interesting structures.

| S-EPMC2711528 | biostudies-literature

Effective synthesis of bicyclodienes via palladium-catalyzed asymmetric allylic alkylation and ruthenium-catalyzed cycloisomerization.

Project description:[n.3.0]Bicycles (n = 3-6) can be synthesized using palladium-catalyzed asymmetric allylic alkylation followed by ruthenium-catalyzed cycloisomerization. New types of triarylphosphino-1,2-diaminooxazoline ligands show the same high levels of enantioselectivity observed with Trost ligand when employed in Pd-catalyzed allylic alkylation reactions. The enyne products of these allylic alkylation reactions were further elaborated using a Ru-catalyzed redox isomerization process, for which a mechanism is proposed.

| S-EPMC7772093 | biostudies-literature

Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Acyclic α-<i>N</i>-Pyrrolyl/Indolyl Ketones.

Project description:The synthesis of fully substituted α-N-pyrrolyl and indolyl ketones via enantioselective palladium-catalyzed allylic alkylation is described. The acyclic ketones are alkylated in high yields with high enantioselectivities through the use of an electron-deficient phosphinooxazoline ligand, furnishing a highly congested and synthetically challenging stereocenter. The obtained alkylation products contain multiple reactive sites poised for additional functionalizations and diversification.

| S-EPMC7608871 | biostudies-literature

Enantioselective Synthesis of Acyclic ?-Quaternary Carboxylic Acid Derivatives through Iridium-Catalyzed Allylic Alkylation.

Project description:The first highly enantioselective iridium-catalyzed allylic alkylation that provides access to products bearing an allylic all-carbon quaternary stereogenic center has been developed. The reaction utilizes a masked acyl cyanide (MAC) reagent, which enables the one-pot preparation of ?-quaternary carboxylic acids, esters, and amides with a high degree of enantioselectivity. The utility of these products is further explored through a series of diverse product transformations.

| S-EPMC5674796 | 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