We present an efficient asymmetric hydrogenation of in situ generated unsaturated lactams catalyzed by N,P-iridium complexes. This strategy offers great advantages in terms of time, atom economy, and reduction of wastes. Moreover, this methodology would enable a one-pot synthesis of enantioenriched pyrrolidones and isoindolinones, which are common motifs in several natural and biologically active compounds. Mechanistic studies revealed the critical and cooperative roles of the acid, anhydride additive, and solvent in governing both reactivity and enantioselectivity. Hydrogenation of the isolated enamide and deuterium-labeling studies support the involvement of competing pathways and highlight the mechanistic advantages of the tandem protocol.

Carbocation rearrangement is a powerful tool for converting a simple precursor into a complex molecular scaffold. However, controlling the stereoselectivity of a reaction that involves carbocation rearrangement is challenging and remains elusive. In this study, we demonstrate a novel iridium-catalyzed Wagner–Meerwein rearrangement and asymmetric hydrogenation of carbocation precursors (1-(aryl)-1-(1-methylcyclobutyl/cyclopentyl) ethan-1-ol) for the synthesis of various optically active gem-dimethyl cycloalkanes. Hence, enantiopure gem-dimethyl-containing compounds are important motifs found in many natural products, and some are FDA-approved drugs. Our methodology starts with an iridium-catalyzed formal deoxygenation of tertiary alcohols to generate a tertiary carbocation that triggers the Wagner–Meerwein rearrangement via the ring expansion and alkyl migration cascade to furnish a stable tertiary-benzyl carbocation. Sequential olefination and in situ asymmetric hydrogenation provide access to various gem-dimethyl chiral cycloalkanes in excellent yield (> 99%) and enantioselectivity (ee up to > 99%). Otherwise, establishing a high yield and enantioselectivity in a saturated cyclic hydrocarbon next to a sterically hindered gem-dimethyl group would not be possible by conventional methods.

A divergent N,P-iridium-catalyzed asymmetric hydrogenation of cyclic dienones into chiral cyclohexenones, cyclohexanones, or cyclohexanols is described. The π-bonds in cyclic dienones underwent hydrogenation in a sequential manner, favoring the (s)-cis conformed alkene followed by the olefin in the (s)-trans conformation and at last the ketone, to install up to three stereocenters in a single step. The simple choice of the proper catalyst allowed the formation of each respective product in high yield and stereopurity (up to 99% ee, up to 99/1 d.r.). This protocol provides an interesting opportunity to access multiple and stereopure carbocycles starting from the same precursor that otherwise require multistep syntheses.

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. Herein, the stereocontrolled hydrogenation of enones to saturated alcohols is described, enabled by orthogonal dual iridium catalysis, using molecular hydrogen for both reductions. In this one-pot procedure, N,P-iridium catalysts (hydrogenation active towards olefins) and NHC,P-iridium catalysts (hydrogenation active towards ketones) operated independently of one another allowing the construction of two contiguous stereogenic centers up to 99 % ee, 99/1 d.r. Ultimately, by simple selection of the chirality of either ligands, the enone could be efficiently reduced to all four stereoisomers of the saturated alcohol in equally high stereopurity. This degree of stereocontrol for the synthesis of different stereoisomers by dual transition-metal catalyzed hydrogenation was previously not attained. The generality in substituted enones (alkyl, aryl, heteroaryl) demonstrate the wide applicability of this concept.

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). No hydrogenation of the C=N π-bond was observed under the applied reaction conditions (20 bar H2, rt, DCM). It was demonstrated that the chiral oxime ether could be hydrolyzed into the ketone with complete preservation of the installed stereogenity at the α-carbon. At last, a binding mode of the substrate to the active iridium catalyst and the consequence for the stereoselective outcome was proposed.

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.

The transition metal-catalyzed asymmetric hydrogenation of carbon–carbon double bonds is recognized as one of the most straightforward methods for the preparation of stereopure compounds. Chiral cyclic motifs have widespread applications in organic synthesis and can also be prepared via this strategy. This review summarizes the recent advances (2016–2023) in the stereoselective metal-catalyzed hydrogenation of cyclic α,β-unsaturated ketones, lactams and lactones since considerable developments in this regard were made. The applications of these methodologies in synthesis are also outlined where relevant.

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. Herein, the reactivity of a conjugated carbonyl compound as a function of their conformational freedom is studied, based on a combined experimental and theoretical approach. It was found that alkenes in the (s)-cis conformation experience a large rate acceleration while (s)-trans restrained alkenes undergo hydrogenation slowly. Ultimately, this reactivity aspect was exploited in a novel method for the monohydrogenation of dienes based on conformational restriction ((s)-cis vs (s)-trans). This mode of discrimination conceptually differs from existing monohydrogenations and dienones constructed of two olefins similar in nature could efficiently be hydrogenated to the chiral alkene (up to 99 % ee). The extent of regioselection is even powerful enough to overcome the conventional reactivity order of substituted olefins (di>tri>tetra). This high yielding and atom-economical protocol provides an interesting opportunity to instal a stereogenic center on a carbocycle, while leaving a synthetically useful alkene untouched.

α-Chiral amines represent a frequently observed functional group in pharmaceuticals. Here, the synthesis of such motifs (up to 91% ee) is described by asymmetric hydrogenation of imines catalyzed by NHC,P-iridium complexes. The hydrogenation proceeded smoothly, even under balloon pressure of hydrogen atmosphere. Mechanistic experiments indicated that the reduction most likely advances by a combination of direct hydrogenation and a hydrogen transfer process using either H₂ or iPrOH as the reductant, respectively. 

The catalytic asymmetric hydrogenation of olefins constitutes a powerful method for the preparation of chiral compounds. A series of prochiral unsaturated amides were efficiently reduced with high enantioselectivities by means of an iridium N,P-complex-catalyzed hydrogenation. Its application in the synthesis of fenpropidin and the possibility of using isomeric mixtures of starting materials are attractive features of the method.