Iridium-Catalyzed Enantioselective Research Articles

Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism.

Despite half a century's advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, the enantioselective hydrogenation of purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe a chiral PCNOx-pincer iridium complex for asymmetric transfer hydrogenation of this alkene class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to the redox isomerization of disubstituted alkenols, producing a tertiary stereocenter remote to the resulting carbonyl group. Mechanistic studies reveal a dihydride species, (PCNOx)Ir(H)2, as the catalytically active intermediate, which can decay to a dimeric species (κ3-PCNOx)IrH(μ-H)2IrH(κ2-PCNOx) via a ligand-remetalation pathway. The catalyst deactivation under the hydrogenation conditions with H2 is much faster than that under the transfer hydrogenation conditions with EtOH, which explains why the (PCNOx)Ir catalyst is effective for the transfer hydrogenation but ineffective for the hydrogenation. The suppression of di-to-trisubstituted alkene isomerization by regioselective 1,2-insertion is partly responsible for the success of this system, underscoring the critical role played by the pincer ligand in enantioselective transfer hydrogenation of 1,1-dialkylethenes. Moreover, computational studies elucidate the significant influence of the London dispersion interaction between the ligand and the substrate on enantioselectivity control, as illustrated by the complete reversal of stereochemistry through cyclohexyl-to-cyclopropyl group substitution in the alkene substrates.

Iridium-Catalyzed Enantioselective Cascade Allylic Etherification/[2+2] Photocycloaddition

Iridium-Catalyzed Enantioselective Cascade Allylic Etherification/[2+2] Photocycloaddition

Iridium-Catalyzed Enantioselective Alkene Hydroalkylation via a Heteroaryl-Directed Enolization-Decarboxylation Sequence.

Upon exposure to a cationic Ir(I)-complex modified with the chiral diphosphine DuanPhos, hydroalkylations of styrenes and α-olefins with diverse heteroaryl tert-butyl acetates occur with complete branched selectivity and very high enantioselectivity. The initial adducts undergo acid promoted decarboxylation in situ to provide alkylated heteroarenes possessing defined β-stereocenters. The processes are postulated to proceed via a stereodefined chiral Ir-enolate, which arises upon heteroarene directed enolization of the heteroaryl acetate precursor. The method can be classified as an enantioselective decarboxylative C(sp3)-C(sp3) cross-coupling.

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.

Iridium-Catalyzed Enantioselective and Diastereodivergent Propargylic C(sp3)–H Allylation

Key words alkynes - allylation - allylic ethers - 1,5-enynes - iridium catalysis - propargylic C−H functionalization

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 Allylic Alkylation

Iridium-Catalyzed Enantioselective Allylic Alkylation

Iridium-Catalyzed Enantioselective Borylation Reaction

Iridium-Catalyzed Enantioselective Borylation Reaction

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 Decarboxylative Allylic Etherification

Iridium-Catalyzed Enantioselective Decarboxylative Allylic Etherification

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.

Iridium-Catalyzed Enantioselective Polyene Cyclization

A highly enantioselective polycyclization method has been developed using the combination of Lewis acid activation with iridium-catalyzed allylic substitution. This strategy relies on direct use of branched, racemic allylic alcohols and furnishes a diverse and unique set of carbo- and heteropolycyclic ring systems in good yields and ≥99% ee.

ChemInform Abstract: Iridium Catalyzed Enantioselective Hydrogenation of α‐Alkoxy and β‐Alkoxy Vinyl Ethers.

AbstractA variety of functionalized acid‐sensitive vinyl ethers is successfully hydrogenated in the presence of a chiral Ir—N‐carbene—oxazoline complex (ICOC).

Application of Phosphine-Phosphite Ligands in the Iridium Catalyzed Enantioselective Hydrogenation of 2-Methylquinoline

The hydrogenation of 2-methylquinoline with Ir catalysts based on chiral phosphine-phosphites has been investigated. It has been observed that the reaction is very sensitive to the nature of the ligand. Optimization of the catalyst, allowed by the highly modular structure of these phosphine-phosphites, has improved the enantioselectivity of the reaction up to 73% ee. The influence of additives in this reaction has also been investigated. Contrary to the beneficial influence observed in related catalytic systems, iodine has a deleterious effect in the present case. Otherwise, aryl phosphoric acids produce a positive impact on catalyst activity without a decrease on enantioselectivity.

Iridium Catalyzed Enantioselective Hydrogenation of N-Iminopyridinium Ylides: Mechanistic Insights

Mechanistic insights of the efficient iridium catalyzed asymmetric hydrogenation of N-iminopyridinium ylides are reported. Using NMR and mass spectrometry, the nature of the pre-catalyst and role of iodine was studied. The effect of solvent as well as an extensive ligand screening is presented. Deuteration experiments also show that C-H(D) insertion pathways occur in competition with the hydrogenation process.

Phosphinomethyloxazolines as Efficient Ligands for the Iridium-Catalyzed Enantioselective Hydrogenation of Unfunctionalized Tetrasubstituted Olefins

- Iridium-catalyzed enantioselective hydrogenation has become the method of choice for the enantioselective reduction of unfunctionalized olefins. In particular, tetrasubstituted olefins are interesting substrates, which allow the generation of two adjacent stereocenters in a single hydrogenation step. For this class of substrates, chiral phosphinomethyl-oxazolines have proved to be very efficient ligands. Herein we report a short and practical synthesis of differently substituted phosphinomethyl-oxazolines and the corresponding iridium(COD) complexes. The scope of these catalysts is demonstrated by hydrogenation studies of four tetrasubstituted olefins.

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.