Olefins are among the most useful chemicals in industry, serving as feedstocks in the large-scale production of high-value-added polymers, fibers, food, pharmaceuticals, and agrochemicals1. An important challenge in the construction of olefins is the creation of the carbon–carbon double bonds in a defined manner of selectivity and stereochemistry, i.e., the E- versus Z-isomer2,3. This is particularly important because of the close relationship between geometry and function, as well as reducing the effort required to separate these isomers (a difficult task)4. Although several strategies to access olefins have been established, e.g., the classic Wittig, Peterson, and Takai olefinations, control of the E/Z selectivity in olefin formation has long been challenging5. Transition-metal catalysis has the ability to afford high selectivity, as evident in transformations of H2-semihydrogenation, in the creation of olefinic C–C bonds6. Pd-based Lindlar catalyst has been commonly used in industry for alkyne semihydrogenation in the selective production of Z-olefins7. Recently, the notable H2-semihydrogenation of alkynes with homogeneous metal catalysts reported by Elsevier8, Arnold9, and Toste10 allows for selectively accessing Z-olefins11,12,13,14. When ruthenium, iron, and cobalt complexes are used, the E-isomers can be predominantly formed with high selectivity (Fig. 1a)15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37. Compared with the achievement of either E- or Z-selectivity, control of both the E- and Z-selectivity by two different ligands with the same metal catalysis has proved to be difficult. There are a few systems that depend on transfer hydrogenation with borrowing a hydride38; however, because hydride sources generate large amounts of waste, in light of increasing demands for sustainability, the hydride-borrowing strategies are impractical for the preparation of olefins on a large scale.

Fig. 1: Controlling the stereochemistry in alkyne hydrogenation for highly selective formation of E- and Z-olefins.
figure 1

a Commonly used strategy in the control of the E- and Z-selectivity by two different metal catalysis. b Controlling the E- and Z-selectivity in the hydrogenation of alkynes by two CAAC ligands. CAAC cyclic (alkyl)(amino)carbene, CAAC-P–Cr CAAC-phosphino-ligated Cr complex 1a, CAAC-N–Cr CAAC-imino-ligated Cr complex 1b.

In this work, we describe progress made in addressing the key stereochemical challenges in using two ligands in control of the selectivity in E- and Z-olefin formation by the hydrogenation of alkynes with molecular hydrogen (Fig. 1b). We develop a bidentate metal catalyst with earth-abundant chromium by chelation with a cyclic (alkyl)(amino)carbene (CAAC) ligand that contains a phosphino anchor, and accomplishes the trans-hydrogenation of alkynes in selectively giving E-olefins39,40,41. Building on this foundation, we establish that tuning the stereoselectivity achieves a bulky imino-incorporated CAAC ligand, resulting in the predominant formation of Z-olefins by Cr catalysis.


Reaction development

Metal-catalyzed hydrogenation of alkynes with H2 provides a clean and sustainable strategy for the formation of olefins, featuring 100% atom efficiency42,43,44,45,46,47. Controlling both the E- and Z-selectivity in alkyne hydrogenation by two different ligands is of great interest, which allows us to access on demand both E- and Z-olefins in high efficiency with the same metal catalysis. We anticipated that the hydrogenation of alkynes by low-cost chromium catalysts could occur by the cis-addition of hydrogen to C–C triple bonds, to form Z-olefins, which can be potentially attacked by a Cr–H species, to afford the alkylated chromate intermediates II (Fig. 2a)48. Subsequent transformations would involve at least three possible pathways, specifically, the reversible β-hydride elimination, rotation of C–C bonds and following β-hydride elimination, and straightforward reductive elimination, thus resulting in the formation of Z-olefins, E-isomers, and over-hydrogenated alkanes, respectively. However, controlling the stereochemistry of hydrogenation by two ligands for forming both Z- and E-olefins in high efficiency has been a long-standing challenge with the same metal catalysis. It may be due to the lack of effective ligands by the same metal catalysis to address the two critical mechanistic issues: (a) inhibiting rotation of the C–C bond of alkylated metal complexes II for selectively accessing a Z-olefin, and (b) facilitating the C–C bond rotation in the main formation of an E-olefin. In addition, the inhibition of reductive elimination of metal hydride II is indispensable for avoiding over-hydrogenation during the processes.

Fig. 2: Hypothesis for controlling both the E- and Z-selectivity by two ligands with Cr catalysis and CAAC-controlled stereoselective hydrogenation of alkynes.
figure 2

a Working hypothesis. b Preparing complex 1a. c Exploring the ligand effect on controlling the E/Z selectivity. The stereoselectivity of E-olefin relative to Z-stereomer was determined by GC analysis.

Catalyst development

Cyclic (alkyl)(amino)carbenes (CAACs) are more nucleophilic and electrophilic than more commonly used N-heterocyclic carbenes (NHCs)39,49. The use of CAACs as ligands in promoting the Rh-catalyzed stereoselective hydrogenation of arenes has been reported50,51,52,53, as well as in assisting the Cr-catalyzed deoxygenative hydroboration of nitro motifs54. Given the different electronic properties and steric circumstances between phosphino and imino substituents, the installation of diphenylphosphino motif within the side chain of CAAC ligand led to bidentate complex 1a with Cr (Fig. 2b)55. Its structure was confirmed by X-ray diffraction analysis, showing an octahedral geometry at Cr in coordination with the phosphino CAAC ligand, three chloride ligands, and an additional acetonitrile ligand.

Exploring the effect of ligands on hydrogenation of alkynes

We explored the effect of CAAC ligands of Cr complexes on the E/Z selectivity in catalytic hydrogenation of diphenylethyne, with magnesium as a reductant, for forming reactive Cr in situ56,57,58,59,60,61,62. The phosphino-containing complex 1a has the ability to promote the addition of hydrogen to a triple bond in a trans-selective manner, affording E-stilbene (E-3a) with up to 99:1 E/Z selectivity (Fig. 2c). By contrast, complex 1b that contains an imino anchor in a CAAC ligand allows for controlling the stereoselectivity of hydrogen addition to affording 99:1 Z/E selectivity. The replacement of the 2,6-di-isopropylphenyl substituent of the imino in 1b by a phenyl (1c) led to low conversion and Z-selectivity (see Supplementary Information). Performing the hydrogenation with complex 1b at ambient temperature and high pressure did not lead to hexaphenylbenzene, giving high conversion and selectivity of Z-stilbene. In these cases, only trace amounts of over-reduced 1,2-diphenylethane were detected.

Scope of CAAC-P ligand-enabled trans-hydrogenation

Using complex 1a, diarylacetylenes containing alkyl substituents undergo the trans-hydrogenation smoothly, affording access to E-olefins (E-3cf) in good yields and with high selectivity (Fig. 3). As expected, the alkenyl substituent in the alkyne substrate is retained in the hydrogenation and then provides a strategy to construct alkenyl-substituted E-stilbene (E-3g). The incorporation of OH and NH2 groups into precursors does not inhibit the hydrogenation of alkynes (E-3h and i). Common functionalities of methoxy, trimethylsilyl, pinacol boronate ester and amino are compatible with the hydrogenation system (E-3jm). Hydrogenation with furanyl-, thiophenyl-, and pyridyl-containing alkynes enables stereoselectively accessing E-alkenyl-substituted heteroarene products (E-3nq). Through hydrogenation, functionalized E-olefins of styrylthiochromane, styryl-dihydrobenzo[b][1,4]dioxine, and styryl-9H-fluorene are stereoselectively accessible (E-3rt). The strategy was extended to hydrogenate alkyl aryl alkynes, affording alkylarylated olefins with 99:1 E/Z selectivity (E-3ux). The CAAC-P–Cr-catalyzed trans-hydrogenation of dialkylalkynes occurs smoothly, providing access to E-dialkylalkene compounds E-3y and 3z in good selectivity. Alkynes that a silicon or boron functional group is directly connected with the reactive triple bonds and have rarely been hydrogenated in the stereoselective formation of olefins. Interestingly, silyls that are directly connected to the alkynes are tolerated in the system, offering a strategy to access a range of E-silylated alkenes E-3aaag in up to >99:1 E/Z selectivity. Boronate ester-substituted alkyne undergoes hydrogenation in a trans-selective manner, resulting in the formation of E-borylated alkene E-3ah. The incorporation of a silyloxy into the alkyl substituent does not affect the stereoselectivity to afford E-alkene (E-3ai).

Fig. 3: CAAC-P ligand-enabled E-selectivity of hydrogenation of alkynes with chromium catalysis.
figure 3

Substrate scope for E-selective hydrogenation of alkynes.

Scope of CAAC-imino ligand-enabled cis-hydrogenation

By control of the stereochemistry with complex 1b, Z-stilbenes that contain a variety of functionalities such as chloride, fluoride, ester, amide, hydroxyl, and naphthyl (Z-3ajao) can be formed in good yields and with high selectivity (Fig. 4). The hydrogenation strategy was successfully used in the construction of Z-styrylanilines Z-3i and Z-3aq containing medicinally interesting amino functionality. Aryl- and alkyl-substituted alkynes undergo hydrogenation smoothly without influencing the Z-selectivity (Z-3x and -3ar). Compared with hydrogenating alkynes without ortho-substituents in the aryls (Z-3as and -3u), excellent Z-selectivity was obtained when ortho-isopropyl- or phenyl-substituted aryl alkynes were used (Z-3at and -3au). This indicates that sterically congested alkynes may facilitate the delivery of high Z-selectivity in the hydrogenation. Alkynes containing two aliphatic substituents of butyl and pentyl readily undergo hydrogenation, leading to the formation of Z-olefins with 99:1 Z/E selectivity (Z-3ax and -3ay). Hydrogenation of the alkyne with a biologically active androsta-5,16-dien-3-ol scaffold enables the synthesis of a Z-olefin derivative in excellent yield and excellent selectivity (Z-3az). Using the CAAC-imino–Cr complex, alkynes that a silyl or phosphino substituent is directly connected with the triple bonds are hydrogenated effectively, giving high Z-selectivity in the formation of compounds of Z-3babc.

Fig. 4: Z-selective hydrogenation of alkynes enabled by CAAC-imino ligand.
figure 4

Substrate scope for Z-selective hydrogenation of alkynes.

Gram-scale hydrogenation and application in accessing E- and Z-olefin-bearing derivatives

Applying the E/Z selectivity controllable hydrogenation strategy, we then hydrogenated alkyne precursors related to the industrially produced E- and Z-stereoselective anetholes (5) and isoeugenol (7) on a one-gram scale with 0.5 mol% of CAAC–Cr precatalysts (Fig. 5). Polyphenolic phytoalexins of E- and Z-resveratrol derivatives (9) were readily accessible by the hydrogenation of alkynes. Hydrogenation afforded pharmaceutically interesting estradiol-derived E- and Z-olefin derivatives in high efficiency (11). In the presence of CAAC-P–Cr complex 1a, the two alkynyl in diethylstilbestrol-containing alkyne (12) are hydrogenated in the formation of the olefin derivative, with extraordinary E/Z selectivity (>99:1). By contrast, CAAC-imino-ligated Cr complex 1b selectively hydrogenates one of the triple bonds, while another alkynyl functionality remains intact, thus affording the alkynyl- and alkenyl-containing derivative Z-13 with 99:1 Z/E selectivity.

Fig. 5: Gram-scale hydrogenation and application in the efficient synthesis of both E- and Z-selective olefin derivatives.
figure 5

a Gram-scale hydrogenation in forming food additives. b Gram-scale hydrogenation in forming fragrance-relevant molecules. c Application in the synthesis of resveratrol derivatives. d The synthesis of estradiol derivatives. e The synthesis of diethylstilbestrol derivatives.


Kinetic studies

The reaction time course with CAAC-P-ligated Cr complex 1a suggested that Z-stilbene was mainly formed at the early stage of hydrogenation, whereas it was sluggishly consumed after 6 h, probably by a cis-to-trans geometrical isomerization (Fig. 6a). This is in line with an increased rate for the formation of E-stilbene, giving yields from 11% to 57%, with complete consumption of alkyne within 2 h. In contrast, the hydrogenation using CAAC-imino-ligated complex 1b mainly gives Z-olefins, which almost do not convert into the related E-stereomer during the process.

Fig. 6: Mechanistic studies of controlling the E/Z selectivity by CAAC ligands.
figure 6

a Reaction profile for the E/Z selective hydrogenation with complexes 1a and 1b. b Studying the cis-to-trans isomerization with complex 1b. c Hydrogenation catalyzed by the resting species IV. d Steric maps of CAAC–Cr(0). e Comparison of electronic parameters of two bidentate CAAC ligands.

Mechanistic studies

To gain insight into achieving high Z-selectivity with 1b, the possibility of the stereoisomerization of Z-3a was examined. The almost twofold formation of E-stilbene relative to CAAC-imino–Cr was observed when <8 mol% of 1b was used (Fig. 6b). Analysis of the resulting complex by 1H nuclear magnetic resonance spectroscopy and high-resolution mass spectroscopy indicates that the formation of a resting species IV by chelation of E-stereomer with CAAC-imino–Cr in a 2:1 ratio may be considered, in which Cr adopts the zero-valent state, based on analysis by X-ray photoelectron spectroscopy (see Supplementary Information). The use of a large amount of CAAC-imino–Cr complex in reactions (e.g., 10 mol%) mainly gives an over-hydrogenated alkane, probably because of the high concentration of catalyst resulting in direct olefin hydrogenation. Although the resting species is inefficient in the catalytic stereoisomerization of Z-olefins, it could promote the catalytic hydrogenation of alkyne, which is in agreement with its good performance in the achievement of high Z-selectivity (Fig. 6c).

The effect of steric circumstances around the Cr centers in complexes 1a and 1b was investigated by calculation of the percentage buried volume (%Vbur) and topographic steric map of their optimized structure of CAAC–Cr(0) (Fig. 6d). Compared with CAAC-phosphino-bearing Cr(0) derived from 1a, the steric map for CAAC-imino-ligated Cr(0) shows a higher percentage buried volume by occupying a different portion of the space around the Cr with the ligand (73.7% vs. 70.9%), causing greater steric congestion in the reactive pocket. We next studied the electronic parameter of these bidentate CAAC ligands, by preparing their coordinated Cr carbonyl complexes by literature methods and measuring the IR spectra (Fig. 6e)63. Comparing the values of the ν(C = O) vibration indicate that a strong electron-donating character of CAAC-phosphino ligand relative to CAAC-imino in the Cr complexes is considered64,65. The alkyne hydrogenation using CAAC–Cr complexes may initially lead to the formation of Z-olefins, which can be stereo-isomerized with sterically less bulky and more electron-rich CAAC-phosphino–Cr 1a in giving E-stereomers. Theoretical studies by density functional theory (DFT) calculations suggest that the stereoisomerization of Z-3a with reactive CAAC-phosphino–Cr–H species occurs by a pathway involving hydrometalation and β-hydride elimination, by overcoming low reaction energies in forming E-3a (Supplementary Data 1 contains the cartesian coordinates of the structures). In contrast, the use of CAAC-imino–Cr–H in the stereoisomerization is unfavorable in energy because of relatively higher activation barriers. The structure of related transition state (TS-9N) for the difficult β-hydride elimination step shows a congested circumstance in the reactive pocket, wherein the steric repulsion was mainly caused by the proximity of two diisopropyl phenyl groups of CAAC-imino and phenyl substituents of olefins. Analysis of the charge population of TS-9N suggested that the charge distributions on the chromated Colefin moiety have limited change compared with that of the related transition state (TS-10P) with CAAC-phosphino (see Supplementary Information), unlike their relatively large difference in Cr–Colefin bond distance, indicating a minor contribution of the electronic features of the ligand on the stereoisomerization. The major role of the steric effect of these CAAC ligands on such unique selectivity may be considered. We hypothesize that the crowded circumstances in the reactive pocket with 1b are unfavorable to the stereoisomerization of cis-olefins, but presumably, allow hydrogenation of alkynes because of the relatively strong coordination between alkynes and metals. This may account for the inefficiency of the CAAC-imino–Cr complex in the stereoisomerization of olefins, and therefore high Z-selectivity is attained in the hydrogenation.

In conclusion, we have devised strategies that allow for alkyne hydrogenation to proceed in an E- and Z-selectivity-controllable manner with two distinct bidentate CAAC ligands by Cr catalysis. The feasibility of using two CAAC ligands by modifying anchors to control both the E- and Z-selectivity of hydrogenation enhances the potential effect of this strategy. With the environmental and cost benefits that catalytic hydrogenation brings to chemical synthesis, these ligand-controllable and stereo-complementary approaches enable the large-scale, sustainable, and selective H2-hydrogenation of simple alkynes to produce on-demand valuable sets of E- and Z-olefins in high efficiency. This is particularly relevant to cases where there are electronic and steric differences between the two CAAC ligand anchors66,67,68,69. The methods described above are expected to lead to the design of robust metal catalysts for developing ligand-controlled selective reactions in the efficient construction of industrially important chemicals.


General procedure of CAAC-phosphino–Cr-catalyzed trans-selective hydrogenation of alkynes for the synthesis of E-olefins

In a Schlenk tube were placed alkyne 2 (0.2 mmol), 1a (1–9 mol%), Mg (10 mg), TMSCl (13 μL), and THF (2 mL) under an atmosphere of nitrogen. The tube was quickly moved to a high-pressure autoclave and stirred under an atmosphere of H2 (6–15 atm) at 90–100 °C for 24 h. After quenching with HClaq (2 mL, 1 M), the crude product was extracted with ethyl acetate (3 × 4 mL). The combined organic phases were dried over anhydrous Na2SO4 and concentrated under a vacuum. The stereoselectivity of E-olefin relative to Z-stereomer was determined by GC analysis or 1H NMR prior to purification. The crude product was purified by silica gel chromatography to afford the related olefin compound.

General procedure of CAAC-Imino–Cr-catalyzed Cis-selective hydrogenation of alkynes for the synthesis of Z-olefins

In a Schlenk tube were placed 1b (1–10 mol%), alkyne 2 (0.2 mmol), Mg (10 mg), 4 Å MS (25 mg), TMSCl (25 μL), and THF (2 mL) under an atmosphere of nitrogen. The tube was quickly moved to a high–pressure autoclave and stirred under an atmosphere of H2 (40–50 atm) at 40–50 oC for 24 h. After quenching with HClaq (2 mL, 1 M), the crude product was extracted with ethyl acetate (3 × 4 mL). The combined organic phases were dried over anhydrous Na2SO4 and concentrated under a vacuum. The stereoselectivity of the Z-olefin relative to E-stereomer was determined by GC analysis or 1H NMR prior to purification. The crude product was purified by silica gel chromatography to afford the desired olefin product.

Spectroscopic methods

1H and 13C NMR spectra were recorded on a Bruker DRX-400 (operating at 400 MHz for 1H and 100 MHz for 13C). GC–MS spectra were recorded on an Agilent Technologies 7890B GC-system with an Agilent 5977B MSD and an HP-5MS column (0.25 mm × 30 m × 0.25 μm). High-resolution mass spectra (HRMS) were recorded on the Exactive Mass Spectrometer (Thermo Scientific, USA) equipped with ESI ionization source. X-ray photoelectron spectroscopy (XPS) data were collected with a Thermo Fisher ESCALAB Xi+ spectrometer equipped with monochromatic Al Kα radiation. IR spectra were recorded on a PerkinElmer spectrum two spectrometers using the transmittance method. Electron paramagnetic resonance (EPR) spectroscopic measurements were performed on the Bruker A300 spectrometer. Elemental analysis (EA) spectroscopic measurements were recorded on the Elemantar Vario EL cube.

Single-crystal X-ray structure determinations

The crystal data of 1a were collected on a Bruker SMART CCD diffractometer with MoKα radiation (λ = 0.71073 Å). The structures were solved by direct methods and refined on F2 using SHELXTL. All nonhydrogen atoms were refined anisotropically.