Copper-Catalyzed Asymmetric Allylic Alkylation Research Articles

Desymmetrization of Inert meso-Diethers through Copper-Catalyzed Asymmetric Allylic Alkylation with Grignard Reagents.

We have developed a highly regio-, diastereo-, and enantioselective Cu-catalyzed desymmetrization of inert meso-diethers using Grignard reagents. Moreover, previous inaccessible sterically hindered organometallic reagents are realized in the reaction with broad secondary alkyl Grignard reagents. Finally, detailed control experiments and density functional theory calculations revealed the desymmetrization of meso-diethers exploits a direct anti-SN2' pathway, in the absence of an in situ-generated allyl bromine intermediate. The following oxidative addition is the crucial rate-determining and enantioselectivity-determining step.

Copper-catalyzed asymmetric allylic alkylation of racemic inert cyclic allylic ethers under batch and flow conditions.

Highly enantioselective Cu-catalyzed asymmetric allylic alkylation of racemic inert cyclic allylic ethers is accomplished in this work. The use of Grignard reagents in combination with BF3·OEt2 and CuBr·SMe2/L2 is the key to enable employment of long-challenging low reactive allylic substrates in this AAA reaction. In addition, the approach exhibited a remarkable superiority in the construction of a stereogenic center involving challenging sterically hindered nucleophiles for both primary and secondary alkyl groups. Extension of this method under continuous flow conditions was also performed with excellent enantioselectivity in a short residence time. Mechanistic experiments indicated that the reaction proceeded through an in situ generated allylic bromide intermediate. All these advantages demonstrated that this chiral catalytic system is a valuable complement for existing asymmetric catalytic methods.

Copper-Catalyzed Asymmetric Allylic Alkylation of Homoenolates Derived from Cyclopropanols

Copper-Catalyzed Asymmetric Allylic Alkylation of Homoenolates Derived from Cyclopropanols

Readily Accessible Unsymmetrical Unsaturated 2,6-Diisopropylphenyl N-Heterocyclic Carbene Ligands. Applications in Enantioselective Catalysis.

A new multicomponent procedure was applied to the synthesis of (a)chiral bulky unsymmetrical unsaturated 2,6-diisopropylphenyl N-heterocyclic carbene (NHC) precursors with excellent selectivity (up to 95%) and good yields. This approach offers access to new chiral NHC ligands, which have found successful applications in both copper-catalyzed asymmetric allylic alkylation and copper-catalyzed asymmetric borylation.

Iterative catalyst controlled diastereodivergent synthesis of polypropionates

Polypropionates are synthesized using a combination of a copper-catalyzed asymmetric allylic alkylation, ruthenium-catalyzed cross-metathesis and iridium-catalyzed asymmetric allylic etherification.

Regio- and enantioselective copper-catalyzed allylic alkylation of ortho-substituted cinnamyl bromides with Grignard reagents.

A highly efficient method for the copper-catalyzed asymmetric allylic alkylation of ortho-substituted cinnamyl bromides with Grignard reagents is reported. The use of a catalytic system comprising CuBr·SMe2 and TaniaPhos as chiral ligands gives rise to a range of branched products with excellent regio- and enantioselectivity.

ChemInform Abstract: Synthesis of Optically Active β‐ or γ‐Alkyl‐Substituted Alcohols Through Copper‐Catalyzed Asymmetric Allylic Alkylation with Organolithium Reagents.

ChemInformVolume 45, Issue 5 Preparative Organic Chemistry ChemInform Abstract: Synthesis of Optically Active β- or γ-Alkyl-Substituted Alcohols Through Copper-Catalyzed Asymmetric Allylic Alkylation with Organolithium Reagents. Sureshbabu Guduguntla, Sureshbabu Guduguntla Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorMartin Fananas-Mastral, Martin Fananas-Mastral Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorBen L. Feringa, Ben L. Feringa Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this author Sureshbabu Guduguntla, Sureshbabu Guduguntla Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorMartin Fananas-Mastral, Martin Fananas-Mastral Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorBen L. Feringa, Ben L. Feringa Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this author First published: 16 January 2014 https://doi.org/10.1002/chin.201405041Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume45, Issue5February 4, 2014 RelatedInformation

Synthesis of Optically Active β- or γ-Alkyl-Substituted Alcohols through Copper-Catalyzed Asymmetric Allylic Alkylation with Organolithium Reagents

An efficient one-pot synthesis of optically active β-alkyl-substituted alcohols through a tandem copper-catalyzed asymmetric allylic alkylation (AAA) with organolithium reagents and reductive ozonolysis is presented. Furthermore, hydroboration-oxidation following the Cu-catalyzed AAA leads to the corresponding homochiral γ-alkyl-substituted alcohols.

Mechanistic identification and improvement of a direct enantioconvergent transformation in copper-catalyzed asymmetric allylic alkylation

Recently, our group reported on the development of an unprecedented process in copper-catalyzed Asymmetric Allylic Alkylation. This method allowed for the quantitative transformation of a racemic substrate into an enantioenriched product. While a high level of asymmetric induction (up to 99% ee) was observed, the mechanistic understanding of the reaction remained fuzzy. In the present article, a thorough mechanistic analysis, based on computational investigations, led to the identification of the reaction pathway. Notably, it uncovered that both enantiomers of the starting material converged independently to the same product via two different mechanistic routes. This specific feature established this process as a rare example of Direct Enantioconvergent Transformation. Finally, the modelling results prompted a valuable improvement of the reaction, relying on the use of a more accessible range of substrates.

Progress in Copper-Catalyzed Asymmetric Allylic Alkylation Reaction

Progress in Copper-Catalyzed Asymmetric Allylic Alkylation Reaction

Copper‐catalyzed divergent kinetic resolution of racemic allylic substrates

When a racemic mixture is fully consumed the products may still be enantiomerically enriched. In particular, the regiodivergent kinetic resolution is a process in which a single chiral catalyst or reagent reacts with a racemic substrate to form regioisomers possessing an opposite configuration on the newly-formed stereogenic centers. This review reports the major advances in the field of the copper-catalyzed regiodivergent and stereodivergent kinetic resolution of allylic substrates with organometallic reagents. The chiral recognition matching phenomena found with particular allylic substrates with the absolute configuration of the chiral catalyst allows in some cases an excellent control of the regio- and stereoselectivity, sheding some light on the so-called "black-box" mechanism of a copper-catalyzed asymmetric allylic alkylation.

Stereoselective synthesis of syn and anti 1,2-hydroxyalkyl moieties by Cu-catalyzed asymmetric allylic alkylation

A stereoselective synthesis of 1,2-hydroxyalkyl moieties is described herein. These valuable building blocks are obtained with complete regiocontrol and excellent stereocontrol both for the syn or the anti products, by choosing the appropriate enantiomer of the ligand in a copper-catalyzed asymmetric allylic alkylation of δ-alkoxy-substituted allyl bromides.

Chelating Hydroxyalkyl NHC as Efficient Chiral Ligands for Room-Temperature Copper-Catalyzed Asymmetric Allylic Alkylation

The application of chiral chelating hydroxy NHC in copper-catalyzed asymmetric allylic alkylation (Cu-AAA) involving various dialkylzincs and allylic phosphate substrates is reported here. From a library of 11 chiral chelating hydroxyalkyl NHC, a fine-tuning has been done to identify the best architectural features enabling to produce the expected γ-adducts in total regioselectivity, good isolated yields, and excellent enantioselectivities (ranging from 93% to >98% ee).

Chiral Cycloalkenes by an Asymmetric Allylic Alkylation-RCM Procedure

Copper-catalyzed asymmetric allylic alkylation reactions (AAA) allow the addition of hard nucleophiles (e.g., Grignard reagents) to electrophiles with high enantioselectivity. This method is limited to prochiral substrates and the use of chiral cyclic electrophiles is not possible. The authors present a method to overcome this restriction by using AAA of achiral linear substrates, followed by an RCM to furnish the desired cyclic compounds.