Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Acyclic quaternary centers from asymmetric conjugate addition of alkylzirconium reagents to linear trisubstituted enones.

ABSTRACT: Synthetic methods for the selective formation of all carbon quaternary centres in non-cyclic systems are rare. Here we report highly enantioselective Cu-catalytic asymmetric conjugate addition of alkylzirconium species to twelve different acyclic trisubstituted enones. A variety of sp³-hybridized nucleophiles generated by in situ hydrozirconation of alkenes with the Schwartz reagent can be introduced, giving linear products bearing quaternary centres with up to 98% ee. The method is tolerant of several important functional groups and 27 total examples are reported. The method uses a new chiral nonracemic phosphoramidite ligand in a complex with copper triflate as the catalyst. This work allows the straightforward stereocontrolled formation of a valuable structural motif using only a catalytic amount of chiral reagent.

SUBMITTER: Gao Z

PROVIDER: S-EPMC5358539 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Acyclic quaternary centers from asymmetric conjugate addition of alkylzirconium reagents to linear trisubstituted enones.

Gao Zhenbo Z Fletcher Stephen P SP

Chemical science 20160902 1

Synthetic methods for the selective formation of all carbon quaternary centres in non-cyclic systems are rare. Here we report highly enantioselective Cu-catalytic asymmetric conjugate addition of alkylzirconium species to twelve different acyclic trisubstituted enones. A variety of sp<sup>3</sup>-hybridized nucleophiles generated by <i>in situ</i> hydrozirconation of alkenes with the Schwartz reagent can be introduced, giving linear products bearing quaternary centres with up to 98% ee. The meth ...[more]

PMID: 28451211

Similar Datasets

Synthesis of Quaternary Carbon Stereogenic Centers by Diastereoselective Conjugate Addition of Boron-Stabilized Allylic Nucleophiles to Enones.

Project description:A method for the site-selective and diastereoselective conjugate addition of boron-stabilized allylic nucleophiles to α,β-unsaturated ketones is disclosed. Transformations involve easily prepared γ,γ-disubstituted allyldiboron reagents and proceed in the presence of a fluoride activator at 80 °C. Reactions proceed with a wide variety of enones and allyldiboron reagents efficiently to deliver ketone products that contain otherwise difficult-to-access vicinal β-tertiary and γ-quaternary carbon stereogenic centers and an alkenylboron moiety. The utility of the method is highlighted by several transformations, including cross-coupling and carbocyclizations.

| S-EPMC7289652 | biostudies-literature

Synthesis of diverse ?-quaternary ketones via palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enones.

Project description:The development and optimization of a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enone conjugate acceptors is described. These reactions employ air-stable and readily-available reagents in an operationally simple and robust transformation that yields ?-quaternary ketones in high yields and enantioselectivities. Notably, the reaction itself is highly tolerant of atmospheric oxygen and moisture and therefore does not require the use of dry or deoxygenated solvents, specially purified reagents, or an inert atmosphere. The ring size and ?-substituent of the enone are highly variable, and a wide variety of ?-quaternary ketones can be synthesized. More recently, the use of NH4PF6 has further expanded the substrate scope to include heteroatom-containing arylboronic acids and ?-acyl enone substrates.

| S-EPMC4598955 | biostudies-literature

Palladium-catalyzed asymmetric conjugate addition of arylboronic acids to five-, six-, and seven-membered ?-substituted cyclic enones: enantioselective construction of all-carbon quaternary stereocenters.

Project description:The first enantioselective Pd-catalyzed construction of all-carbon quaternary stereocenters via 1,4-addition of arylboronic acids to ?-substituted cyclic enones is reported. Reaction of a wide range of arylboronic acids and cyclic enones using a catalyst prepared from Pd(OCOCF(3))(2) and a chiral pyridinooxazoline ligand yields enantioenriched products bearing benzylic stereocenters. Notably, this transformation is tolerant to air and moisture, providing a practical and operationally simple method of synthesizing enantioenriched all-carbon quaternary stereocenters.

| S-EPMC3087848 | biostudies-literature

Conjugate addition of lithiated methyl pyridines to enones.

Project description:Preparatively useful conjugate addition of lithiated methyl pyridines to cyclic and acyclic enones is reported. Addition of 2-picoline to 3-penten-2-one led to a concise synthesis of the alkaloids (+/-)-senepodine G and (+/-)-cermizine C.

| S-EPMC2921646 | biostudies-literature

Asymmetric Ni-catalyzed conjugate allylation of activated enones.

Project description:The nickel-catalyzed enantioselective addition of allylboronic acid pinacol ester, allylB(pin), is described. This reaction is highly effective with dialkylidene ketones and favors the allylation of the benzylidene site in nonsymmetric substrates. The reaction appears to proceed by conversion of the dialkylidene ketone substrate to an unsaturated pi-allyl complex (I), followed by reductive elimination. Enantioselectivities range from 91 to 94% ee for a range of substrates when chiral ligand 14 is employed.

| S-EPMC3065355 | biostudies-literature

Mechanistic analysis of an asymmetric palladium-catalyzed conjugate addition of arylboronic acids to β-substituted cyclic enones.

Project description:An asymmetric palladium-catalyzed conjugate addition reaction of arylboronic acids to enone substrates was investigated mechanistically. Desorption electrospray ionization coupled to mass spectrometry was used to identify intermediates of the catalytic cycle and delineate differences in substrate reactivity. Our findings provide evidence for the catalytic cycle proceeding through formation of an arylpalladium(II) cation, subsequent formation of an arylpalladium-enone complex, and, ultimately, formation of the new C-C bond. Reaction monitoring in both positive and negative ion modes revealed that 4-iodophenylboronic acid formed a relatively stable trimeric species under the reaction conditions.

| S-EPMC4338963 | biostudies-literature

Enantioselective synthesis of boron-substituted quaternary carbon stereogenic centers through NHC-catalyzed conjugate additions of (pinacolato)boron units to enones.

Project description:The first examples of Lewis base catalyzed enantioselective boryl conjugate additions (BCAs) that generate products containing boron-substituted quaternary carbon stereogenic centers are disclosed. Reactions are performed in the presence of 1.0-5.0?mol% of a readily accessible chiral accessible N-heterocyclic carbene (NHC) and commercially available bis(pinacolato)diboron; cyclic or linear ?,?-unsaturated ketones can be used and rigorous exclusion of air or moisture is not necessary. The desired products are obtained in 63-95% yield and 91:9 to >99:1 enantiomeric ratio (e.r.). The special utility of the NHC-catalyzed approach is demonstrated in the context of an enantioselective synthesis of natural product antifungal (-)-crassinervic acid.

| S-EPMC4094110 | biostudies-literature

Efficient Synthesis of Chiral Trisubstituted 1,2-Allenyl Ketones by Catalytic Asymmetric Conjugate Addition of Malonic Esters to Enynes.

Project description:An N,N'-dioxide/scandium(III) complex catalyzed, highly efficient conjugate addition of malonic esters to enynes is described. A range of trisubstituted 1,2-allenyl ketones were obtained in high yields (up to 99?%) with good d.r. (up to 95/5) and excellent ee values (97?%-99?%). Moreover, the products could be easily transformed into chiral furan and 5-hydroxypyrazoline derivatives, both of which are important skeletons of many biologically active compounds and pharmacologicals.

| S-EPMC4738401 | biostudies-literature

Nickel-catalyzed reductive conjugate addition to enones via allylnickel intermediates.

Project description:An alternative method to copper-catalyzed conjugate addition followed by enolate silylation for the synthesis of ?-disubstituted silyl enol ether products (R(1)(R(2))HCCH?C(OSiR(4)(3))R(3)) is presented. This method uses haloarenes instead of nucleophilic aryl reagents. Nickel ligated to either neocuproine or bipyridine couples an ?,?-unsaturated ketone or aldehyde (R(2)HC?CHC(O)R(3)) with an organic halide (R(1)-X) in the presence of a trialkylchlorosilane reagent (Cl-SiR(4)(3)). Reactions are assembled on the benchtop and tolerate a variety of functional groups (aldehyde, ketone, nitrile, sulfone, pentafluorosulfur, and N-aryltrifluoroacetamide), electron-rich iodoarenes, and electron-poor haloarenes. Mechanistic studies have confirmed the first example of a catalytic reductive conjugate addition of organic halides that proceeds via an allylnickel intermediate. Selectivity is attributed to (1) rapid, selective reaction of LNi(0) with chlorotriethylsilane and enone in the presence of other organic electrophiles, and (2) minimization of enone dimerization by ligand steric effects.

| S-EPMC3547151 | biostudies-literature

Enantioselective Palladium-Catalyzed Alkenylation of Trisubstituted Alkenols To Form Allylic Quaternary Centers.

Project description:In this report, we describe the generation of remote allylic quaternary stereocenters ?, ?, and ? relative to a carbonyl in high enantioselectivity. We utilize a redox-relay Heck reaction between alkenyl triflates and acyclic trisubstituted alkenols of varying chain-lengths. A wide array of terminal (E)-alkenyl triflates are suitable for this process. The utility of this functionalization is validated further by conversion of the products, via simple organic processes to access remotely functionalized chiral tertiary acid, amine, and alcohol products.

| S-EPMC5152571 | 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