Browse
Submit Data
Databases
API
Help

Dataset Information

35 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Highly diastereoselective chelation-controlled additions to ?-silyloxy ketones.

ABSTRACT: The polar Felkin-Anh, Cornforth-Evans, and Cram-chelation models predict that the addition of organometallic reagents to silyl-protected ?-hydroxy ketones proceeds via a nonchelation pathway to give anti-diol addition products. This prediction has held true for the vast majority of additions reported in the literature, and few methods for chelation-controlled additions of organometallic reagents to silyl-protected ?-hydroxy ketones have been introduced. Herein, we present a general and highly diastereoselective method for the addition of dialkylzincs and (E)-di-, (E)-tri-, and (Z)-disubstituted vinylzinc reagents to ?-silyloxy ketones using alkyl zinc halide Lewis acids, RZnX, to give chelation-controlled products (dr ?18:1). The compatibility of organozinc reagents with other functional groups makes this method potentially very useful in complex molecule synthesis.

SUBMITTER: Stanton GR

PROVIDER: S-EPMC3112462 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Highly diastereoselective chelation-controlled additions to α-silyloxy ketones.

Stanton Gretchen R GR Koz Gamze G Walsh Patrick J PJ

Journal of the American Chemical Society 20110502 20

The polar Felkin-Anh, Cornforth-Evans, and Cram-chelation models predict that the addition of organometallic reagents to silyl-protected α-hydroxy ketones proceeds via a nonchelation pathway to give anti-diol addition products. This prediction has held true for the vast majority of additions reported in the literature, and few methods for chelation-controlled additions of organometallic reagents to silyl-protected α-hydroxy ketones have been introduced. Herein, we present a general and highly di ...[more]

PMID: 21534530

Similar Datasets

Diastereoselective chelation-controlled additions to ?-silyloxy aldehydes.

Project description:A general diastereoselective method for the addition of dialkylzincs and (E)-di- and (E)-trisubstituted vinylzinc reagents to ?-silyloxy aldehydes is presented. This method employs alkyl zinc triflate and nonaflate Lewis acids and affords chelation-controlled products (6:1 to > 20:1 dr).

| S-EPMC3401491 | biostudies-literature

Overriding Felkin control: a general method for highly diastereoselective chelation-controlled additions to alpha-silyloxy aldehydes.

Project description:According to the Felkin-Anh and Cram-chelation models, nucleophilic additions to alpha-silyloxy aldehydes proceed through a nonchelation pathway due to the steric and electronic properties of the silyl group, giving rise to Felkin addition products. Herein we describe a general method to promote chelation-control in additions to alpha-silyloxy aldehydes. Dialkylzincs, functionalized dialkylzincs, and (E)-disubstituted, (E)-trisubstituted, and (Z)-disubstituted vinylzinc reagents add to silyl-protected alpha-hydroxy aldehydes with high selectivity for chelation-controlled products (dr of 10:1 to >20:1) in the presence of alkylzinc halides or triflates, RZnX. With the high functional group tolerance of organozinc reagents, the mild Lewis acidity of RZnX, and the excellent diastereoselectivities favoring the chelation-controlled products, this method will be useful in the synthesis of natural products. A mechanism involving chelation is supported by (1) NMR studies of a model substrate, (2) a dramatic increase in reaction rate in the presence of an alkylzinc halide, and (3) higher diastereoselectivity with larger alkyl substituents on the alpha-carbon of the aldehyde. This method provides access to chelation-controlled addition products with high diastereoselectivity previously unavailable using achiral organometallic reagents.

| S-EPMC2850917 | biostudies-literature

Diastereoselective Additions of Allylmagnesium Reagents to α-Substituted Ketones When Stereochemical Models Cannot Be Used.

Project description:The stereoselectivities of reactions of allylmagnesium reagents with chiral ketones cannot be easily explained by stereochemical models. Competition experiments indicate that the complexation step is not reversible, so nucleophiles cannot access the widest range of possible encounter complexes and therefore cannot be analyzed easily using available models. Nevertheless, additions of allylmagnesium reagents to a ketone can still be stereoselective provided that the carbonyl group adopts a conformation that leads to one face being completely blocked from the approach of the allylmagnesium reagent.

| S-EPMC9022487 | biostudies-literature

Alkenes as Chelating Groups in Diastereoselective Additions of Organometallics to Ketones.

Project description:Alkenes have been discovered to be chelating groups to Zn(II), enforcing highly stereoselective additions of organozincs to ?,?-unsaturated ketones. 1H NMR studies and DFT calculations provide support for this surprising chelation mode. The results expand the range of coordinating groups for chelation-controlled carbonyl additions from heteroatom Lewis bases to simple C-C double bonds, broadening the 60 year old paradigm.

| S-EPMC4195513 | biostudies-literature

Hypervalent Iodine-Mediated Diastereoselective α-Acetoxylation of Cyclic Ketones.

Project description:A binary hybrid system comprising a hypervalent iodine(III) reagent and BF3•OEt2 Lewis acid was found to be effective for the diastereoselective α-acetoxylation of cyclic ketones. In this hybrid system, BF3•OEt2 Lewis acid allowed the activation of the hypervalent iodine(III) reagent and cyclic ketones for smooth α-acetoxylation reaction, achieving high diastereoselectivity. This hypervalent iodine-mediated α-acetoxylation of the cyclic ketone reaction plausibly undergoes an SN2 substitution mechanism via an α-C-bound hypervalent iodine intermediate. The diastereoselectivity of the reaction mainly originates from thermodynamic control.

| S-EPMC7365914 | biostudies-literature

Highly efficient diastereoselective reduction of alpha-fluoroimines.

Project description:A highly selective reduction of alpha-fluoroimines to the corresponding beta-fluoroamines has been developed utilizing trichlorosilane as the reductant. The key aspect of this reaction is the ability of fluorine and nitrogen to activate organosilanes leading to high diastereoselectivity (>100:1) in the product distribution. This new method provides a new avenue for the diastereoselective synthesis of beta-fluorinated amines in good yields and selectivity.

| S-EPMC2929650 | biostudies-literature

Iridium-Catalyzed Diastereoselective and Enantioselective Allylic Substitutions with Acyclic α-Alkoxy Ketones.

Project description:The asymmetric alkylation of acyclic ketones is a longstanding challenge in organic synthesis. Reported herein are diastereoselective and enantioselective allylic substitutions with acyclic α-alkoxy ketones catalyzed by a metallacyclic iridium complex to form products with contiguous stereogenic centers derived from the nucleophile and electrophile. These reactions occur between allyl methyl carbonates and unstabilized copper(I) enolates generated in situ from acyclic α-alkoxy ketones. The resulting products can be readily converted into enantioenriched tertiary alcohols and tetrahydrofuran derivatives without erosion of enantiomeric purity.

| S-EPMC4969080 | biostudies-literature

Enantio- and Diastereoselective 1,2-Additions to α-Ketoesters with Diborylmethane and Substituted 1,1-Diborylalkanes.

Project description:The catalytic enantioselective synthesis of boronate-substituted tertiary alcohols through additions of diborylmethane and substituted 1,1-diborylalkanes to α-ketoesters is reported. The reactions are catalyzed by readily available chiral phosphine/copper(I) complexes and produce β-hydroxyboronates containing up to two contiguous stereogenic centers in up to 99:1 e.r. and greater than 20:1 d.r. The utility of the organoboron products is demonstrated through several chemoselective functionalizations. Evidence indicates the reactions occur via an enantioenriched α-boryl-copper-alkyl intermediate.

| S-EPMC5000392 | biostudies-literature

Generating Stereodiversity: Diastereoselective Fluorination and Highly Diastereoselective Epimerization of α-Amino Acid Building Blocks.

Project description:Diastereoselective fluorination of N-Boc ( R)- and ( S)-2,2-dimethyl-4-((arylsulfonyl)methyl)oxazolidines and a previously unknown diastereoselective epimerization at the fluorine-bearing carbon atom α to the sulfone was realized. Diastereoselectivities of both reactions were excellent for benzothiazolyl sulfones, allowing access to two enantiomerically pure diastereomers from one chiral precursor. To demonstrate synthetic utility, the benzothiazolyl sulfones were converted to diastereomerically pure ( S, S)- and ( R, S)-benzyl sulfones via sulfinate salts and to amino acids. To understand the diastereoselectivities, DFT analysis was performed.

| S-EPMC8117975 | biostudies-literature

Asymmetric construction of acyclic quaternary stereocenters via direct enantioselective additions of α-alkynyl ketones to allenamides.

Project description:Acyclic quaternary stereocenters are widely present in a series of biologically active natural products and pharmaceuticals. However, development of highly efficient asymmetric catalytic methods for the construction of these privileged motifs represents a longstanding challenge in organic synthesis. Herein, an efficient chiral phosphoric acid catalyzed direct asymmetric addition of α-alkynyl acyclic ketones with allenamides has been developed, furnishing the acyclic all-carbon quaternary stereocenters with excellent regioselectivities and high enantioselectivities. Extensive and detailed experimental mechanistic studies were performed to investigate the mechanism of this reaction. Despite a novel covalent allyl phosphate intermediate was found in these reactions, further studies indicated that a SN2-type mechanism with the ketone nucleophiles is not very possible. Instead, a more plausible mechanism involving the elimination of the allyl phosphate to give the α,β-unsaturated iminium intermediate, which underwent the asymmetric conjugate addition with the enol form of ketone nucleophiles under chiral anion catalysis, was proposed. In virtue of the fruitful functional groups bearing in the chiral products, the diverse derivatizations of the chiral products provided access to a wide array of chiral scaffolds with quaternary stereocenters.

| S-EPMC8602376 | 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