Stereocontrolled Hydrogenation of Conjugated Enones to Alcohols via Dual Iridium-Catalysis.

The concept of dual catalysis is an emerging area holding high potential in terms of preparative efficiency, yet faces severe challenges in compatibility of reaction conditions and interference of catalysts. The transition-metal catalyzed stereoselective hydrogenation of olefins and ketones typically proceeds under different reaction conditions and/or uses a different reductant. As a result, these two types of hydrogenations can normally not be performed in the same pot.

Asymmetric Synthesis and Applications of Chiral Organoselenium Compounds: A Review.

The synthesis and application of organoselenium compounds have developed rapidly, and chiral organoselenium compounds have become an important intermediate in the field of medicine, materials, organic synthesis. The strategy of developing a green economy is still a challenge in the synthesis of chiral organoselenium compounds with enantioselective properties. This review covers in detail the synthesis of chiral organoselenium compounds from 1979 to 2024 and their application in the fields of asymmetric synthesis and catalysis.

Asymmetric and Chemoselective Iridium Catalyzed Hydrogenation of Conjugated Unsaturated Oxime Ethers.

Research on the chemoselective metal-catalyzed hydrogenation of conjugated π-systems has mostly been focussed on enones. Herein, we communicate the understudied asymmetric hydrogenation of enimines catalyzed by N,P-iridium complexes and chemoselective toward the alkene. A number of enoxime ethers underwent hydrogenation smoothly to yield the desired products in high yield and stereopurity (up to 99 % yield, up to 99 % ee).

The Effect of Conformational Freedom vs Restriction on the Rate in Asymmetric Hydrogenation: Iridium-Catalyzed Regio- and Enantioselective Monohydrogenation of Dienones.

Transition metal-catalyzed asymmetric hydrogenation constitutes an efficient strategy for the preparation of chiral molecules. When dienes are subjected to hydrogenation, control over regioselectivity still presents a large challenge and the fully saturated alkane is often yielded. A few successful monohydrogenations of dienes have been reported, but hitherto these are only efficient for dienes comprised of two distinctly different olefins.

Iridium-Catalyzed Double Convergent 1,3-Rearrangement/Hydrogenation of Allylic Alcohols.

Enantioconvergent catalysis has the potential to convert different isomers of a starting material to a single highly enantioenriched product. Here we report a novel enantioselective double convergent 1,3-rearrangement/hydrogenation of allylic alcohols using an Ir-N,P catalyst. A variety of allylic alcohols, each consisting of a 1:1:1:1 mixture of four isomers, were converted to the corresponding tertiary alcohols with two contiguous stereogenic centers, in up to 99% and 99:1 .

The Implications of the Brønsted Acidic Properties of Crabtree-Type Catalysts in the Asymmetric Hydrogenation of Olefins.

Chiral iridium complexes derived from Crabtree's catalyst are highly useful in modern hydrogenations of olefins attributed to high reactivity, stereoselectivity, and stability. Despite that these precatalysts are pH neutral, the reaction mixtures turn acidic under hydrogenation conditions. This Perspective is devoted to the implications of the intrinsic Brønsted acidity of catalytic intermediates in asymmetric hydrogenation of olefins.

Catalytic enantioselective synthesis of fluoromethylated stereocenters by asymmetric hydrogenation.

Fluoromethyl groups possess specific steric and electronic properties and serve as a bioisostere of alcohol, thiol, nitro, and other functional groups, which are important in an assortment of molecular recognition processes. Herein we report a catalytic method for the asymmetric synthesis of a variety of enantioenriched products bearing fluoromethylated stereocenters with excellent yields and enantioselectivities. Various N,P-ligands were designed and applied in the hydrogenation of fluoromethylated olefins and vinyl fluorides.

Stereoselective Iridium-N,P-Catalyzed Double Hydrogenation of Conjugated Enones to Saturated Alcohols.

Asymmetric hydrogenation of prochiral substrates such as ketones and olefins constitutes an important instrument for the construction of stereogenic centers, and a multitude of catalytic systems have been developed for this purpose. However, due to the different nature of the π-system, the hydrogenation of olefins and ketones is normally catalyzed by different metal complexes. Herein, a study on the effect of additives on the Ir-N,P-catalyzed hydrogenation of enones is described.

Synthesis of Chiral Tetrahydro-3-benzazepine Motifs by Iridium-Catalyzed Asymmetric Hydrogenation of Cyclic Ene-carbamates.

A highly efficient N,P-ligated iridium complex is presented for the simple preparation of chiral tetrahydro-3-benzazepine motifs by catalytic asymmetric hydrogenation. Substrates bearing both 1-aryl and 1-alkyl substituents were smoothly converted to the corresponding hydrogenated product with excellent enantioselectivity (91-99% ) and in isolated yield (92-99%). The synthetic value of this transformation was demonstrated by a gram-scale hydrogenation and application in the syntheses of trepipam and fenoldopam.

Iridium-catalyzed enantioconvergent hydrogenation of trisubstituted olefins.

Asymmetric hydrogenation of olefins constitutes a practical and efficient method to introduce chirality into prochiral substrates. However, the absolute majority of the developed methodologies is enantiodivergent and thus require isomerically pure olefins which is a considerable drawback since most olefination strategies produce (E/Z)-mixtures. Although some advances have been reported, a general enantioconvergent hydrogenation featuring a broad functional group tolerance remains elusive.

Combined Theoretical and Experimental Studies Unravel Multiple Pathways to Convergent Asymmetric Hydrogenation of Enamides.

We present a highly efficient convergent asymmetric hydrogenation of / mixtures of enamides catalyzed by N,P-iridium complexes supported by mechanistic studies. It was found that reduction of the olefinic isomers ( and geometries) produces chiral amides with the same absolute configuration (enantioconvergent hydrogenation). This allowed the hydrogenation of a wide range of / mixtures of trisubstituted enamides with excellent enantioselectivity (up to 99% ).

Asymmetric Full Saturation of Vinylarenes with Cooperative Homogeneous and Heterogeneous Rhodium Catalysis.

Homogeneous and heterogeneous catalyzed reactions can seldom operate synergistically under the same conditions. Here we communicate the use of a single rhodium precursor that acts in both the homogeneous and heterogeneous phases for the asymmetric full saturation of vinylarenes that, to date, constitute an unmet bottleneck in the field. A simple asymmetric hydrogenation of a styrenic olefin, enabled by a ligand accelerated effect, accounted for the facial selectivity in the consecutive arene hydrogenation.

Kinetic resolution of racemic allylic alcohols iridium-catalyzed asymmetric hydrogenation: scope, synthetic applications and insight into the origin of selectivity.

Asymmetric hydrogenation is one of the most commonly used tools in organic synthesis, whereas, kinetic resolution asymmetric hydrogenation is less developed. Herein, we describe the first iridium catalyzed kinetic resolution of a wide range of trisubstituted secondary and tertiary allylic alcohols. Large selectivity factors were observed in most cases ( up to 211), providing the unreacted starting materials in good yield with high levels of enantiopurity (ee up to >99%).

Site- and Enantioselective Iridium-Catalyzed Desymmetric Mono-Hydrogenation of 1,4-Dienes.

The control of site selectivity in asymmetric mono-hydrogenation of dienes or polyenes remains largely underdeveloped. Herein, we present a highly efficient desymmetrization of 1,4-dienes via iridium-catalyzed site- and enantioselective hydrogenation. This methodology demonstrates the first iridium-catalyzed hydrogenative desymmetriation of meso dienes and provides a concise approach to the installation of two vicinal stereogenic centers adjacent to an alkene.

Asymmetric synthesis of 1,2-fluorohydrin: iridium catalyzed hydrogenation of fluorinated allylic alcohol.

We have developed a simple protocol for the preparation of 1,2-fluorohydrin by asymmetric hydrogenation of fluorinated allylic alcohols using an efficient azabicyclo thiazole-phosphine iridium complex. The iridium-catalyzed asymmetric synthesis of chiral 1,2-fluorohydrin molecules was carried out at ambient temperature with operational simplicity, and scalability. This method was compatible with various aromatic, aliphatic, and heterocyclic fluorinated compounds as well as a variety of polyfluorinated compounds, providing the corresponding products in excellent yields and enantioselectivities.

Highly Enantioselective Iridium-Catalyzed Hydrogenation of Conjugated Trisubstituted Enones.

Asymmetric hydrogenation of conjugated enones is one of the most efficient and straightforward methods to prepare optically active ketones. In this study, chiral bidentate Ir-N,P complexes were utilized to access these scaffolds for ketones bearing the stereogenic center at both the α- and β-positions. Excellent enantiomeric excesses, of up to 99%, were obtained, accompanied with good to high isolated yields.

Cationic NHC-Phosphine Iridium Complexes: Highly Active Catalysts for Base-Free Hydrogenation of Ketones.

Novel bidentate N-heterocyclic carbene-phosphine iridium complexes have been synthesized and evaluated in the hydrogenation of ketones. Reported catalytic systems require base additives and, if excluded, need elevated temperature or high pressure of hydrogen gas to achieve satisfactory reactivity. The developed catalysts showed extremely high reactivity and good enantioselectivity under base-free and mild conditions.

Enantioconvergent and enantiodivergent catalytic hydrogenation of isomeric olefins.

The asymmetric catalytic hydrogenation of olefins is one of the most widely studied and utilised transformations in asymmetric synthesis. This straightforward and atom-economical strategy can provide excellent enantioselectivity for a broad variety of substrates and is widely relevant for both industrial applications and academic research. In many instances the hydrogenation is stereospecific in the regard that the E-Z-geometry of the olefin governs the stereochemistry of the hydrogenation, producing an enantiodivergent outcome.

Stereodivergent Synthesis of Trisubstituted Enamides: Direct Access to Both Pure Geometrical Isomers.

A stereodivergent strategy has been developed to access either ()- or ()-isomers of trisubstituted enamides. Starting from an extensive range of ketones, it was possible to synthesize and isolate the desired pure isomer by switching the reaction conditions. Lewis acid activation enables the formation of the ()-isomers in high stereoselectivity (>90:10) and good yields.

Tandem Peterson olefination and chemoselective asymmetric hydrogenation of β-hydroxy silanes.

Here, we report the first Ir-N,P complex catalyzed tandem Peterson olefination and asymmetric hydrogenation of β-hydroxy silanes. This reaction resulted in the formation of chiral alkanes in high isolated yields (up to 99%) and excellent enantioselectivity (up to 99% ee) under mild conditions. Modification of the reaction conditions provides a choice to transform either an olefin or the β-hydroxy silane in a chemoselective manner.

Asymmetric Synthesis of Alkyl Fluorides: Hydrogenation of Fluorinated Olefins.

The development of new general methods for the synthesis of chiral fluorine-containing molecules is important for several scientific disciplines. We herein disclose a straightforward method for the preparation of chiral organofluorine molecules that is based on the iridium-catalyzed asymmetric hydrogenation of trisubstituted alkenyl fluorides. This catalytic asymmetric process enables the synthesis of chiral fluorine molecules with or without carbonyl substitution.

Diastereo- and Enantioselective Synthesis of Fluorine Motifs with Two Contiguous Stereogenic Centers.

The synthesis of chiral fluorine containing motifs, in particular, chiral fluorine molecules with two contiguous stereogenic centers, has attracted much interest in research due to the limited number of methods available for their preparation. Herein, we report an atom-economical and highly stereoselective synthesis of chiral fluorine molecules with two contiguous stereogenic centers via azabicyclo iridium-oxazoline-phosphine-catalyzed hydrogenation of readily available vinyl fluorides. Various aromatic, aliphatic, and heterocyclic systems with a variety of functional groups were found to be compatible with the reaction and provide the highly desirable product as single diastereomers with excellent enantioselectivities.

Asymmetric Total Synthesis of (-)-Juvabione via Sequential Ir-Catalyzed Hydrogenations.

(-)-Juvabione, a natural sesquiterpene exhibiting juvenile insect hormone activity, was synthesized constructing the two adjacent stereogenic centers via sequential Ir-catalyzed hydrogenations. The first center is generated by hydrogenation of a styrene-type double bond (99% ee). The successive monohydrogenation of a diene intermediate constitutes the key step, granting high levels of regio- and stereocontrol (94:6 dr).

Transition-Metal-Catalyzed Regioselective Asymmetric Mono-Hydrogenation of Dienes and Polyenes.

Organic compounds containing multiple C=C bonds are attractive substrates for catalytic asymmetric hydrogenation. The full saturation of prochiral double bonds, controlling the creation of two or more stereocenters in one step, is obviously a remarkable goal. However, another fascinating and useful option is to selectively introduce a new defined stereogenic center while leaving other double bonds untouched.

Ir-Catalyzed Asymmetric and Regioselective Hydrogenation of Cyclic Allylsilanes and Generation of Quaternary Stereocenters via the Hosomi-Sakurai Allylation.

A number of cyclic dienes containing the allylsilane moiety were prepared by a Birch reduction and subjected to iridium-catalyzed regioselective and asymmetric hydrogenation, which provided chiral allylsilanes in high conversion and enantiomeric excess (up to 99 % ee). The compounds were successively used in the Hosomi-Sakurai allylation with various aldehydes employing TiCl as Lewis acid, providing adducts with two additional stereogenic centers in excellent diastereoselectivity.