Iridium-Catalyzed Enantioselective Allylic Research Articles

Iridium-Catalyzed Enantioselective Allylic Substitution of Vinylcyclopropanes by Carboxylic Acids

An efficient method for a highly regio- and enantioselective allylic substitution of vinylcyclopropanes using carboxylic acids as oxygen nucleophile via iridium catalysis has been developed. This represents a highly atom-economic approach for the synthesis of synthetically useful chiral building blocks in high yields. The practical utility of this method is demonstrated by the application of the products in useful transformations.

Mechanistic Basis for the Iridium-Catalyzed Enantioselective Allylation of Alkenyl Boronates.

Iridium(phosphoramidite) complexes catalyze an enantio- and diastereoselective three-component coupling reaction of alkenyl boronic esters, organolithium reagents, and secondary allylic carbonates. The reaction proceeds through an allylation-induced 1,2-metalate shift of the alkenyl boronate to form non-adjacent stereocenters. Mechanistic investigations outline the overall catalytic cycle and reveal trends in reactivity and selectivity. Analysis of relative stereochemistry in products derived from a variety of 1,1-disubtituted alkenyl boronates provides insight into the transition state of the addition and indicates a concerted pathway. Kinetic analysis of the reaction revealed the kinetic order dependence in boronate, the catalyst, and both the slow- and fast-reacting enantiomer of allylic carbonate as well as the turnover-limiting step of the reaction. Determination of nucleophile-specific parameters N and sN for alkenyl boronate complexes enabled comparison to other classes of nucleophiles. DFT calculations indicate the addition of the alkenyl boronate to the cationic Ir(π-allyl) intermediate and the 1,2-metalate shift occur in a concerted mechanism. The stereoselectivity is determined by ligand-substrate steric repulsions and dispersion interactions in the syn addition transition state. Hammett studies supported the computational results with regard to electronic trends observed with both aryl-derived alkenyl boronates and aryl carbonates.

Iridium-Catalyzed Enantioselective Allylic Substitution with Aqueous Solutions of Nucleophiles.

The iridium-catalyzed asymmetric allylic substitution under biphasic conditions is reported. This approach allows the use of various unstable and/or volatile nucleophiles including hydrazines, methylamine, t-butyl hydroperoxide, N-hydroxylamine, α-chloroacetaldehyde and glutaraldehyde. This transformation provides rapid access to a broad range of products from simple starting materials in good yields and up to >99% ee and 20:1 d.r. Additionally, these products can be elaborated efficiently into a diverse set of cyclic and acyclic compounds, bearing up to four stereocenters.

Iridium-Catalyzed Enantioselective Allylation of Aryl Enamides and Enecarbamates.

Aromatic enamide and enecarbamate as a novel type of nucleophile in the asymmetric allylation of branched, racemic allylic alcohols to give homoallylic ketones has been described. Enabled by Carreira's chiral Ir (P, olefin) complex, the reactions proceed in good yields with excellent enantioselectivities.

Iridium-Catalyzed Enantioselective and Diastereoselective Allylation of Dioxindoles: A One-Step Synthesis of 3-Allyl-3-hydroxyoxindoles.

An iridium-catalyzed asymmetric allylation of dioxindoles, 3-hydroxyoxindoles, regulated by prosthetic groups has been accomplished under mild conditions. The methodology is applicable to a diverse array of 3-hydroxyoxindole and cinnamyl acetate substrates. A range of 3-allyl-3-hydroxyoxindoles containing vicinal tetrasubstituted and trisubstituted stereocenters can be efficiently synthesized in one-step with excellent enantioselectivity (up to >99% enaniomeric excess (ee)) and good diastereoselectivity (up to 11:1 diastereomeric ratio (dr)).

Iridium-Catalyzed Enantioselective Allylic Alkylation

Iridium-Catalyzed Enantioselective Allylic Alkylation

Trimethyl Orthoacetate and Ethylene Glycol Mono-Vinyl Ether as Enolate Surrogates in Enantioselective Iridium-Catalyzed Allylation.

Trimethyl orthoacetate and ethylene glycol mono-vinyl ether are employed in iridium-catalyzed enantioselective allylation reactions. The method documented enables their convenient use as surrogates for silyl ketene acetals and silyl enol ethers to prepare γ,δ-unsaturated esters and protected aldehydes with excellent enantioselectivity. The utility of this novel method has been demonstrated by its implementation in a formal enantioselective synthesis of the meroterpenoid (+)-conicol.

Iridium-Catalyzed Enantioselective Allylic Substitution of Aliphatic Esters with Silyl Ketene Acetals as the Ester Enolates.

Enantioselective allylic substitution with enolates derived from aliphatic esters under mild conditions remains challenging. Herein we report iridium-catalyzed enantioselective allylation reactions of silyl ketene acetals, the silicon enolates of esters, to form products containing a quaternary carbon atom at the nucleophile moiety and a tertiary carbon atom at the electrophile moiety. Under relatively neutral conditions, the allylated aliphatic esters were obtained with excellent regioselectivity and enantioselectivity. These products were readily converted into primary alcohols, carboxylic acids, amides, isocyanates, and carbamates, as well as tetrahydrofuran and γ-butyrolactone derivatives, without erosion of enantiomeric purity.

Iridium-Catalyzed Enantioselective Allylic Substitution of Enol Silanes from Vinylogous Esters and Amides.

The enol silanes of vinylogous esters and amides are classic dienes for Diels-Alder reactions. Here, we report their reactivity as nucleophiles in Ir-catalyzed, enantioselective allylic substitution reactions. A variety of allylic carbonates react with these nucleophiles to give allylated products in good yields with high enantioselectivities and excellent branched-to-linear ratios. These reactions occur with KF or alkoxide as the additive, but mechanistic studies suggest that these additives do not activate the enol silanes. Instead, they serve as bases to promote the cyclometalation to generate the active Ir catalyst. The carbonate anion, which was generated from the oxidative addition of the allylic carbonate, likely activates the enol silanes to trigger their activity as nucleophiles for reactions with the allyliridium electrophile. The synthetic utility of this method was illustrated by the synthesis of the anti-muscarinic drug, fesoterodine.

ChemInform Abstract: Iridium‐Catalyzed Enantioselective Allylic Alkylation with Functionalized Organozinc Bromides.

ChemInformVolume 46, Issue 43 Preparative Organic Chemistry ChemInform Abstract: Iridium-Catalyzed Enantioselective Allylic Alkylation with Functionalized Organozinc Bromides. James Y. Hamilton, James Y. Hamilton ETH Zuerich, CH-8093 Zuerich, Switz.Search for more papers by this authorDavid Sarlah, David Sarlah ETH Zuerich, CH-8093 Zuerich, Switz.Search for more papers by this authorErick M. Carreira, Erick M. Carreira ETH Zuerich, CH-8093 Zuerich, Switz.Search for more papers by this author James Y. Hamilton, James Y. Hamilton ETH Zuerich, CH-8093 Zuerich, Switz.Search for more papers by this authorDavid Sarlah, David Sarlah ETH Zuerich, CH-8093 Zuerich, Switz.Search for more papers by this authorErick M. Carreira, Erick M. Carreira ETH Zuerich, CH-8093 Zuerich, Switz.Search for more papers by this author First published: 08 October 2015 https://doi.org/10.1002/chin.201543027Read 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 onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue43October, 2015 RelatedInformation

Iridium-catalyzed enantioselective allylic alkylation with functionalized organozinc bromides.

Iridium-catalyzed enantioselective allylic alkylation of branched racemic carbonates with functionalized alkylzinc bromide reagents is described. Enabled by a chiral Ir/(P,olefin) complex, the method described allows allylic substitution with various primary and secondary alkyl nucleophiles with excellent regio- and enantioselectivities. The developed reaction was showcased in a concise, asymmetric synthesis of (-)-preclamol.

Iridium-catalyzed enantioselective allylation of silyl enol ethers derived from ketones and α,β-unsaturated ketones.

The unified Ir-catalyzed enantioselective allylic substitution reactions of silyl enol ethers derived from ketones and α,β-unsaturated ketones with branched, racemic allylic alcohols are described. This transformation is catalyzed by the Carreira system and proceeds without fluoride, and with high ee and b : l ratio. The synthetic utility of this method was illustrated by the concise enantioselective total synthesis of marine natural products calyxolane A, B and by the assignment of the absolute configuration of calyxolane A.

Iridium-Catalyzed Enantioselective Allylic Vinylation

Iridium-Catalyzed Enantioselective Allylic Vinylation

Iridium-Catalyzed Enantioselective Allylic Vinylation

The first example of Ir-catalyzed asymmetric substitution reaction with vinyl trifluoroborates is described. The direct reaction between branched, racemic allylic alcohols and potassium alkenyltrifluoroborates proceeded with high site selectivity and excellent enantioselectivity (up to 99%) mediated by an Ir-(P,olefin) complex. This method allows rapid access to various 1,4-dienes or trienes including the biologically active natural products (-)-nyasol and (-)-hinokiresinol.

Synthesis of Enantiopure Allyl Phenyl Sulfides

Asymmetric transition-metal-­catalyzed allylic substitutions are powerful synthetic transformations for the preparation of chiral allylic substrates. Herein, an iridium-catalyzed enantioselective allylation protocol using sodium thio­phenoxide 1 as a nucleophile has been developed. The best selectivities could be achieved with the chiral monodentate phosphoramidite ligand L*(S,S,S a )-5 and CsF as an additive in dichloromethane.

Iridium-Catalyzed Enantioselective Allylic Alkylation

Combination of [Ir(cod)Cl]2 and phosphoramidite 1 is shown to be a very effective catalytic system for enantio- and regioselective allylic alkylation. The advantage of the methodology described here is the use of readily available starting material, mild conditions to yield branched products exclusively.

Iridium-Catalyzed Enantioselective Allylic Substitutions with Aliphatic Nitro Compounds as Prenucleophiles

Enantioselective Ir-catalyzed allylic alkylations with nitroalkanes and ethyl nitroacetate as nucleophiles are reported. Up to 99% ee was achieved using catalysts prepared by in situ activation of mixtures of phosphorus amidites and [Ir(COD)Cl]2. The method was applied to a synthesis of the antidepressant (1S,2R)-trans-2-phenylcyclopentanamine.