Advertisement

Palladium-catalyzed regio- and stereoselective alkoxycarbonylation of unsymmetrical internal alkynes toward α, β-unsaturated succinates

  • Chang-Sheng Kuai
    Affiliations
    Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China

    University of Chinese Academy of Sciences, Beijing, 100049, China
    Search for articles by this author
  • Bing-Hong Teng
    Affiliations
    Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China

    School of Chemistry and Chemical Engineering, Liaoning Normal University, 850 Huanghe Road, Dalian, 116029, China
    Search for articles by this author
  • Yingying Zhao
    Affiliations
    School of Chemistry and Chemical Engineering, Liaoning Normal University, 850 Huanghe Road, Dalian, 116029, China
    Search for articles by this author
  • Xiao-Feng Wu
    Correspondence
    Corresponding author. Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
    Affiliations
    Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China

    University of Chinese Academy of Sciences, Beijing, 100049, China

    Leibniz-Institut für Katalyse e. V., Albert-Einstein-Straβe 29a, Rostock, 18059, Germany
    Search for articles by this author
Open AccessPublished:September 20, 2022DOI:https://doi.org/10.1016/j.tchem.2022.100029

      Abstract

      Succinates play a vital role in industry, pharmaceutics, beverage, and cosmetics. A regio- and stereoselective alkoxycarbonylation of unsymmetrical internal alkynes with alcohols or phenols toward α, β-unsaturated succinates enabled by palladium catalysis has been accomplished under mild conditions. A series of α, β-unsaturated succinates with a broad range of functional groups were obtained in exclusive (E)-stereoselectivity and good yields. Furthermore, (Z)-stereoselectivity α, β-unsaturated can be obtained by a simple photocatalytic isomerization reaction.

      Graphical abstract

      Keywords

      1. 1. Introduction

      Transition-metal-catalyzed carbonylation is a powerful strategy for the synthesis of carbonylated compounds [
      • Quintero-Duque S.
      • Dyballa K.M.
      • Fleischer I.
      Metal-catalyzed carbonylation of alkynes: key aspects and recent development.
      ,
      • Wu X.-F.
      Palladium-catalyzed carbonylative transformation of aryl chlorides and aryl tosylates.
      ,
      • Peng J.-B.
      • Geng H.-Q.
      • Wu X.-F.
      The Chemistry of CO: Carbonylation.
      ,
      • Peng J.-B.
      • Wu F.-P.
      • Wu X.-F.
      First-row transition-metal-catalyzed carbonylative transformations of carbon electrophiles.
      ,
      • Yin Z.
      • Xu J.-X.
      • Wu X.-F.
      No making without breaking: nitrogen-centered carbonylation reactions.
      ,
      • Liu Y.
      • Chen Y.-H.
      • Yi H.
      • Lei A.
      An update on oxidative C–H carbonylation with CO.
      ], which represents a straightforward route for converting carbon monoxide or its surrogate as the C1 building block into value-added carbonyl compounds in an atom-economical manner. Among all types of carbonylative transformations, hydroesterification of alkynes is an important part of catalytic carbonylation, and it is also an important method to synthesize α, β-unsaturated esters with great application [
      • Zhang S.
      • Neumann H.
      • Beller M.
      Synthesis of α,β-unsaturated carbonyl compounds by carbonylation reactions.
      ,
      • Sang R.
      • Hu Y.
      • Razzaq R.
      • Jackstell R.
      • Franke R.
      • Beller M.
      State-of-the-art palladium-catalyzed alkoxycarbonylations.
      ]. Alkoxycarbonylation of alkynes [
      • Kiss G.
      Palladium-catalyzed reppe carbonylation.
      ,
      • Brennführer A.
      • Neumann H.
      • Beller M.
      Palladium-catalyzed carbonylation reactions of alkenes and alkynes.
      ,
      • Boddien A.
      • Gärtner F.
      • Federsel C.
      • Piras I.
      • Junge H.
      • Jackstell R.
      • Beller M.
      • Laurenczy G.
      • Shi M.
      ,
      • Wu X.-F.
      • Fang X.
      • Wu L.
      • Jackstell R.
      • Neumann H.
      • Beller M.
      Transition-metal-catalyzed carbonylation reactions of olefins and alkynes: a personal account.
      ] is more attractive due to its 100% atomic economy and safety compared to the presence of (over)stoichiometric amounts of oxidants with the oxidative alkoxycarbonylation of olefins [
      • James D.E.
      • Hines L.F.
      • Stille J.K.
      The palladium(II) catalyzed olefin carbonylation reaction. The stereochemistry of methoxypalladation.
      ,
      • Pennequin P.
      • Fontaine M.
      • Castanet Y.
      • Mortreux A.
      • Petit F.
      Palladium catalyzed oxidative carbonylation of alkenes by methyl formate.
      ]. However, the regio- and stereoselectivity is a challenge due to the diversity of reaction sites (Scheme 1A). To the best of our knowledge, almost all the protocols that able to properly regulate regio- and stereoselectivity so far are restricted to terminal alkynes. For instance, a series of branched [
      • Drent E.
      • Arnoldy P.
      • Budzelaar P.H.M.
      Efficient palladium catalysts for the carbonylation of alkynes.
      ,
      • Oberhauser W.
      • Ienco A.
      • Vizza F.
      • Trettenbrein B.
      • Oberhuber D.
      • Strabler C.
      • Ortner T.
      • Brüggeller P.
      Regioselective hydromethoxycarbonylation of terminal alkynes catalyzed by palladium(II)–Tetraphos complexes.
      ,
      • Crawford L.E.
      • Cole-Hamilton D.J.
      • Drent E.
      • Bühl M.
      Mechanism of alkyne alkoxycarbonylation at a Pd catalyst with P,N hemilabile ligands: a density functional study.
      ,
      • Queirolo M.
      • Vezzani A.
      • Mancuso R.
      • Gabriele B.
      • Costa M.
      • Della Ca’ N.
      Neutral vs anionic palladium iodide-catalyzed carbonylation of terminal arylacetylenes.
      ,
      • Chen X.
      • Zhu H.
      • Wang W.
      • Du H.
      • Wang T.
      • Yan L.
      • Hu X.
      • Ding Y.
      Multifunctional single-site catalysts for alkoxycarbonylation of terminal alkynes.
      ,
      • Qi H.
      • Huang Z.
      • Wang M.
      • Yang P.
      • Du C.-X.
      • Chen S.-W.
      • Li Y.
      Bifunctional ligands for Pd-catalyzed selective alkoxycarbonylation of alkynes.
      ,
      • Yang D.
      • Liu L.
      • Wang D.-L.
      • Lu Y.
      • Zhao X.-L.
      • Liu Y.
      Novel multi-dentate phosphines for Pd-catalyzed alkoxycarbonylation of alkynes promoted by H2O additive.
      ,
      • Liu D.
      • Ke M.
      • Ru T.
      • Ning Y.
      • Chen F.-E.
      Room-temperature Pd-catalyzed methoxycarbonylation of terminal alkynes with high branched selectivity enabled by bisphosphine-picolinamide ligand.
      ,
      • Zhao K.-C.
      • Liu L.
      • Chen X.-C.
      • Yao Y.-Q.
      • Guo L.
      • Lu Y.
      • Zhao X.-L.
      • Liu Y.
      Multiple-functional diphosphines: synthesis, characterization, and application to Pd-catalyzed alkoxycarbonylation of alkynes.
      ] and linear [
      • Knifton J.F.
      α,β-unsaturated carboxylic esters from alkynes catalyzed by homogeneous palladium complexes.
      ,
      • El Ali B.
      • Alper H.
      Synthesis of unsaturated esters, including t-alkyl esters, by the palladium-catalyzed carbonylation of alkynes in the presence of alcohols and 1,4-bis(diphenylphosphino)butane.
      ,
      • Akao M.
      • Sugawara S.
      • Amino K.
      • Inoue Y.
      Regioselective hydroesterification of 1-alkynes catalyzed by palladium–phosphine complexes.
      ,
      • Núñez Magro A.A.
      • Robb L.-M.
      • Pogorzelec P.J.
      • Slawin A.M.Z.
      • Eastham G.R.
      • Cole-Hamilton D.J.
      Highly selective formation of unsaturated esters or cascade reactions to α,ω-diesters by the methoxycarbonylation of alkynes catalysed by palladium complexes of 1,2-bis(ditertbutylphosphinomethyl)benzene.
      ,
      • Chen X.
      • Zhu H.
      • Wang T.
      • Li C.
      • Yan L.
      • Jiang M.
      • Liu J.
      • Sun X.
      • Jiang Z.
      • Ding Y.
      The 2V-P,N polymer supported palladium catalyst for methoxycarbonylation of acetylene.
      • Yang J.
      • Kong D.
      • Wu H.
      • Shen Z.
      • Zou H.
      • Zhao W.
      • Huang G.
      Palladium-catalyzed regio- and chemoselective double-alkoxycarbonylation of 1,3-diynes: a computational study.
      ] selective α, β-unsaturated esters (the selectivity up to 99:1) can be obtained by designing and modifying the steric hindrance, electronic properties, and proton transfer capacity of ligands applied to enhance the catalyst reactivity and reaction selectivity for the alkoxycarbonylation of alkynes (Scheme 1A, middle).
      Scheme 1
      Scheme 1Catalytic regioselective alkoxycarbonylation of alkynes.
      However, for unsymmetric internal alkynes [
      • Liu J.
      • Yang J.
      • Baumann W.
      • Jackstell R.
      • Beller M.
      Stereoselective synthesis of highly substituted conjugated dienes via Pd-catalyzed carbonylation of 1,3-diynes.
      ,
      • Kuai C.-S.
      • Xu J.-X.
      • Chen B.
      • Wu X.-F.
      Palladium-catalyzed regio- and stereoselective hydroaminocarbonylation of unsymmetrical internal alkynes toward α,β-unsaturated amides.
      ,
      • Kuniyasu H.
      • Yoshizawa T.
      • Kambe N.
      Palladium-catalyzed hydrophenoxycarbonylation of internal alkynes by phenol and CO: the use of Zn for the formation of active catalyst.
      ], less studied and poor regioselectivity is presented, probably due to the difficulty on regio- and stereoselectivity tuning and its low reactivity compared with terminal alkynes (Scheme 1A, right). One exceptional example was reported by the research group of Kuniyasu and Kambe [
      • Kuniyasu H.
      • Yoshizawa T.
      • Kambe N.
      Palladium-catalyzed hydrophenoxycarbonylation of internal alkynes by phenol and CO: the use of Zn for the formation of active catalyst.
      ]. With Pd(OAc)2/dppp catalyst system in the presence of Zn dust as reductant, hydrophenoxycarbonylation of internal alkynes with phenols were realized. Therefore, it is still highly desirable to develop new methodologies for alkoxycarbonylation of unsymmetrical internal alkynes that display high regio- and stereoselectivity.
      Furthermore, the structural motifs of succinate are widely occurring in a variety of pharmaceuticals and biologically active molecules. In addition, it also has a wide range of applications in industry (such as beverages, cosmetics) [
      • Yamaguchi T.
      • Yanagi T.
      • Hokari H.
      • Mukaiyama Y.
      • Kamijo T.
      • Yamamoto I.
      Preparation of optically active succinic acid derivatives. I. Optical resolution of 2-Benzyl-3-(cis-hexahydroisoindolin-2-ylcarbonyl)-propionic acid.
      ,
      • Whittaker M.
      • Floyd C.D.
      • Brown P.
      • Gearing A.J.H.
      Design and therapeutic application of matrix metalloproteinase inhibitors.
      ,
      • Marcq V.
      • Mirand C.
      • Decarme M.
      • Emonard H.
      • Hornebeck W.
      MMPs inhibitors: new succinylhydroxamates with selective inhibition of MMP-2 over MMP-3, Bioorg.
      ,
      • Liu J.
      • Yang Y.
      • Ji R.
      An effective and convenient method for the preparation of KAD-1229.
      ,
      • Carnahan M.A.
      • Grinstaff M.W.
      Synthesis of generational polyester dendrimers derived from glycerol and succinic or adipic acid.
      ,
      Global biosuccinic acid market to reach market volume of 710 kilotonnes by 2020: allied Market Research.
      ]. Accordingly, much effort has been devoted to developing new synthetic methods to establish such a structure (Scheme 1B) [
      • James D.E.
      • Stille J.K.
      The palladium(II) catalyzed olefin carbonylation reaction. Mechanisms and synthetic utility.
      ,
      • Gabriele B.
      • Salerno G.
      • Costa M.
      • Chiusoli G.P.
      Combined oxidative and reductive carbonylation of terminal alkynes with palladium iodide-thiourea catalysts.
      ,
      • Inoue S.
      • Yokota K.
      • Tatamidani H.
      • Fukumoto Y.
      • Chatani N.
      Chelation-assisted transformation: synthesis of 1,4-dicarboxylate esters by the Rh-catalyzed carbonylation of internal alkynes with pyridin-2-ylmethanol.
      ,
      • Huang Q.
      • Hua R.
      An efficient rhodium-catalyzed double hydroaminocarbonylation of alkynes with carbon monoxide and amines affording 1,4-diamide derivatives.
      ,
      • Driller K.M.
      • Klein H.
      • Jackstell R.
      • Beller M.
      Iron-catalyzed carbonylation: selective and efficient synthesis of succinimides.
      ,
      • Gao Y.-X.
      • Chang L.
      • Shi H.
      • Liang B.
      • Wongkhan K.
      • Chaiyaveij D.
      • Batsanov A.S.
      • Marder T.B.
      • Li C.-C.
      • Yang Z.
      • Huang Y.
      A thiourea-oxazoline library with axial chirality: ligand synthesis and studies of the palladium-catalyzed enantioselective bis(methoxycarbonylation) of terminal olefins.
      ,
      • Liu H.
      • Lau G.P.S.
      • Dyson P.J.
      Palladium-catalyzed aminocarbonylation of alkynes to succinimides.
      ,
      • Liu J.
      • Dong K.
      • Franke R.
      • Neumann H.
      • Jackstell R.
      • Beller M.
      Selective palladium-catalyzed carbonylation of alkynes: an atom-economic synthesis of 1,4-dicarboxylic acid diesters.
      ,
      • Yang D.
      • Liu H.
      • Wang D.-L.
      • Luo Z.
      • Lu Y.
      • Xia F.
      • Liu Y.
      Co-catalysis over a bi-functional ligand-based Pd-catalyst for tandem bis-alkoxycarbonylation of terminal alkynes.
      ,
      • Guo W.-D.
      • Liu L.
      • Yang S.-Q.
      • Chen X.-C.
      • Lu Y.
      • Vo-Thanh G.
      • Liu Y.
      Synergetic catalysis for one-pot bis-alkoxycarbonylation of terminal alkynes over Pd/Xantphos−Al(OTf)3 Bi-functional catalytic system.
      ,
      • Zhu L.
      • Liu L.-J.
      • Jiang Y.-Y.
      • Liu P.
      • Fan X.
      • Zhang Q.
      • Zhao Y.
      • Bi S.
      Mechanism and origin of ligand-controlled chemo- and regioselectivities in palladium-catalyzed methoxycarbonylation of alkynes.
      ,
      • Li X.
      • Feng S.
      • Hemberger P.
      • Bodi A.
      • Song X.
      • Yuan Q.
      • Mu J.
      • Li B.
      • Jiang Z.
      • Ding Y.
      Iodide-coordinated single-site Pd catalysts for alkyne dialkoxycarbonylation.
      ,
      • Ji X.
      • Shen C.
      • Tian X.
      • Zhang H.
      • Ren X.
      • Dong K.
      Asymmetric double hydroxycarbonylation of alkynes to chiral succinic acids enabled by palladium relay catalysis.
      ]. For example, Chatani and co-workers accomplished a Rh-catalyzed alkoxycarbonylation of internal alkynes to construct saturated succinates by using special alcohol, pyridine-2-ylmethanol [
      • Inoue S.
      • Yokota K.
      • Tatamidani H.
      • Fukumoto Y.
      • Chatani N.
      Chelation-assisted transformation: synthesis of 1,4-dicarboxylate esters by the Rh-catalyzed carbonylation of internal alkynes with pyridin-2-ylmethanol.
      ]. In 2018, an elegant work was reported by Beller's group [
      • Liu J.
      • Dong K.
      • Franke R.
      • Neumann H.
      • Jackstell R.
      • Beller M.
      Selective palladium-catalyzed carbonylation of alkynes: an atom-economic synthesis of 1,4-dicarboxylic acid diesters.
      ], which successfully achieved a one-pot highly reactive and selective dialkoxycarbonylation of terminal alkynes to synthesize saturated succinates by developing a novel ligand structure. Recently, Dong's group successfully realized the asymmetric dialkoxycarbonylation of terminal alkyne through palladium relay catalysis to construct chiral saturated succinates [
      • Ji X.
      • Shen C.
      • Tian X.
      • Zhang H.
      • Ren X.
      • Dong K.
      Asymmetric double hydroxycarbonylation of alkynes to chiral succinic acids enabled by palladium relay catalysis.
      ]. Compared with the saturated succinates, the α, β-unsaturated succinates are even more attractive for their potential functionalization reactions due to the retention of their unsaturated bonds. Based on our continual interests in catalytic carbonylation, herein, we present a regio- and stereoselective alkoxycarbonylation of unsymmetrical internal alkynes with alcohols or phenols toward α, β-unsaturated succinates enabled by palladium catalysis under mild conditions. A series of α, β-unsaturated succinates with a broad range of functional groups were obtained in exclusive (E)-stereoselectivity and good yields. Furthermore, (Z)-stereoselectivity α, β-unsaturated can be obtained by a simple photocatalytic isomerization reaction (Scheme 1C).

      2. 2. Results and discussion

      At the outset of our work, we employed ethanol and phenylpropiolate as the model substrates, Pd(PPh3)4 and PTSA as the catalytic system under CO pressure (10 ​bar) in THF at 100 ​°C. First, a variety of ligands were evaluated (Table 1, entries 1–7). Monodentate ligands, such as PPh3, PCy3 and nBuPAd2, delivered 3aa and 4aa in moderate to low yields and poor regioselectivities (Table 1, entries 1–3). Then we switched to examine a range of bisphosphine ligands, we found that the bite angle of the ligand exhibited a significant influence on the reactivity and selectivity of this alkoxycarbonylation of alkynes (Table 1, entries 4–7), Xantphos shows excellent selectivity compared with the other bisphosphine ligands giving exclusive 3aa in 74% yield. To test the temperature and the pressure of CO tolerance limit of the reaction, we tried to reduce the temperature from 100 to 30 ​°C and the pressure of CO (10–1 ​bar) (Table 1, entries 8–11), and found that the reaction activity would be decreased if the reaction temperature was lower than 40 ​°C. To our delight, the yield of 3aa increased after reducing the CO pressure to 1 ​bar. Finally, we further examined the catalyst loading, even with 1 ​mol % of the catalyst loading still showed good catalytic efficiency in this transformation (Table 1, entry 11–13).
      Table 1Optimization of reaction conditions
      Reaction conditions: 1a (0.3 ​mmol), 2a (0.2 ​mmol), carbon monoxide (1–10 ​bar), Pd(PPh3)4 (5 ​mol%), ligand (5 ​mol% of bisphosphine and 10 ​mol% of monophosphine), PTSA (10 ​mol%), THF (1.0 ​mL), 40–100 ​°C, 12 ​h.
      ,
      Yield was determined by GC using n-hexadecane as the internal standard.
      .
      EntryLigandT (oC)CO (bar)Yield 3aa (4aa) (%)
      Yield was determined by GC using n-hexadecane as the internal standard.
      1PPh31001062 (10)
      2PCy31001056 (17)
      3nBuPAd21001013 (22)
      4DPPE1001059(12)
      5DPPF1001066 (15)
      6DPEphos1001073 (15)
      7Xantphos1001074 (0)
      8Xantphos501076 (0)
      9Xantphos401075 (0)
      10Xantphos301070 (0)
      11Xantphos40185 (0)
      12Xantphos40182 (0)
      Pd(PPh3)4 (2.5 ​mol%), Xantphos (2.5 ​mol%).
      13Xantphos40184 (0)
      Pd(PPh3)4 (1 ​mol%), Xantphos (1 ​mol%).
      a Reaction conditions: 1a (0.3 ​mmol), 2a (0.2 ​mmol), carbon monoxide (1–10 ​bar), Pd(PPh3)4 (5 ​mol%), ligand (5 ​mol% of bisphosphine and 10 ​mol% of monophosphine), PTSA (10 ​mol%), THF (1.0 ​mL), 40–100 ​°C, 12 ​h.
      b Yield was determined by GC using n-hexadecane as the internal standard.
      c Pd(PPh3)4 (2.5 ​mol%), Xantphos (2.5 ​mol%).
      d Pd(PPh3)4 (1 ​mol%), Xantphos (1 ​mol%).
      With the optimized conditions in hand, a wide range of readily available alcohols and phenols were evaluated. As depicted in Scheme 2, various primary alcohols bearing either electron-withdrawing or electron-donating substituents all successfully afforded the desired α, β-unsaturated succinates with moderate to good yields (3aa-3ga). Furthermore, alcohols possessing functional groups such as chloro (3ha), and even highly reactive iodo, alkenyl and alkynyl moieties (3ia-3ka) behaved well in this reaction. A series of benzyl alcohols are also suitable for this catalytic system, delivering the desired products. For instance, halogenated benzyl alcohol (4-Chloro, 3-bromo), anthracen-9-ylmethanol (3na) and heterocyclic benzyl (3oa, 3pa) all reacted smoothly in good yields under the current conditions. However, the corresponding product of pyridin-3-ylmethanol was not obtained (3qa), which may be due to the coordination effect of pyridine on the reaction. Notably, upon employing ethane-1,2-diol and 1,3-phenylenedimethanol as the reaction partner, only the mono alkoxycarbonylaed products (3ra, 3as) were obtained in 75% and 67% yield, respectively. Moreover, 1-hydroxybenzotriazole was also tolerated and delivered the corresponding α, β-unsaturated succinate products under the standard conditions (3ta). In addition to primary alcohols, secondary and tertiary alcohols with high steric hindrance were also tolerated and delivered the corresponding products in moderate to good yields (3ua-3ya). Finally, several phenols substituted with electron-donating group (-OMe), electron-withdrawing group (-CF3) and functional group (o-alkynyl) were also tolerated and delivered the desired products in 60–81% yields (3za-3ada).
      Scheme 2
      Scheme 2Scope of alcohols and phenolsa. aReaction conditions: 1 (0.3 ​mmol), 2a (0.2 ​mmol), carbon monoxide (1 ​bar), d(PPh3)4 (1 ​mol%), Xantphos (1 ​mol%), PTSA (10 ​mol%), THF (1.0 ​mL), 40 ​°C, 12 ​h, isolated yields.
      Subsequently, the scope of alkynes was then explored under the current conditions, depicted in Scheme 3. The desired α-β-unsaturated succinates 3 ​ab-3aj can be successfully produced with good yields (79%–93%) regardless of the presence of electron-withdrawing, or electron-donating groups at the para, ortho or meta position of the benzene ring. The steric hindered substrates of naphthalene-substituted phenylpropiolate could also be successfully applied in this transformation and given 80% yield of the corresponding product. When thiophene substituted phenylpropionate was applied, the stereoselectivity decreased (78%, E:Z ​= ​8:1). However, pyridine substituted phenylpropionate substrate was not compatible with this reaction system. Different phenylpropionate of alkyl substitutions and phenyl in ester part can be carried out smoothly, and the corresponding α-β-unsaturated succinates product 3an-3aq were obtained with 72–91% yields. However, low yield of the desired product was obtained when ethyl 2-butynoate was tested. Finally, acetylenone and phenylpropanamide were tested without further optimization, and giving the corresponding products (3ar, 3as) in 80%, 69%, respectively.
      Scheme 3
      Scheme 3Scope of alkynesa. aReaction conditions: 1 (0.3 ​mmol), 2a (0.2 ​mmol), carbon monoxide (1 ​bar), Pd(PPh3)4 (1 ​mol%), Xantphos (1 ​mol%), PTSA (10 ​mol%), THF (1.0 ​mL), 40 ​°C, 12 ​h, isolated yields.
      To demonstrate the practical utility of this strategy, several experiments were conducted depicted in Scheme 4. First, the alkoxycarbonylation of 2a was carried out on a 2 ​mmol scale and the desired α, β-unsaturated succinates product was produced in 85% yield (Scheme 4A). Next, two synthesis transformations were carried out with α-β-unsaturated succinate 3aa as the start material. Based on the previous literature about alkenes isomerization [
      • Singh A.
      • Fennell C.J.
      • Weaver J.D.
      Photocatalyst size controls electron and energy transfer: selectable E/Z isomer synthesis via C–F alkenylation.
      ,
      • An X.-D.
      • Zhang H.
      • Xu Q.
      • Yu L.
      • Yu S.
      Stereodivergent synthesis of α-aminomethyl cinnamyl ethers via photoredox-catalyzed radical relay reaction.
      ,
      • Zhang H.
      • Yu S.
      Visible light-promoted isomerization of alkenes.
      ,
      • Wang M.
      • He Y.-Q.
      • Zhu Y.
      • Song Z.-B.
      • Wang X.-Y.
      • Huang H.-Y.
      • Cao B.-P.
      • Tian W.-F.
      • Xiao Q.
      The wavelength-regulated stereodivergent synthesis of (Z)- and (E)-1,4-enediones from phosphonium ylides.
      ], we found that when employed Eosin Y as the catalyst under blue light in acetonitrile, the E-succinate 3aa can successfully convert into less thermodynamically stable Z-isomer 4aa in 89% (Z:E ​= ​10:1). In addition, α, β-unsaturated succinate 3aa can be further hydrolyzed into acid 5aa under simple conditions which provided more options for further transformations (Scheme 4B). Finally, several natural products and bioactive molecule modified alcohols were investigated to verify the practicability of this method. Gratifyingly, biologically active alcohols, such as Nerol (3aea), Testosterone (3afa), Cholesterol (3aga), Pregnenolone (3 ​aha) were all successfully converted into the corresponding α, β-unsaturated succinate products in 72%–82% yields (Scheme 4C). Those results indicate the potential application of this process in the late-stage alkoxycarbonylation of various complex alcohols.
      Scheme 4
      Scheme 4Scale-up reaction, transformations and late-stage modification of bioactive molecules.
      Based on the previous literature on carbonylative reactions and our observations, a plausible catalytic cycle for this alkoxycarbonylation reaction is proposed in Scheme 5. Initially, the active palladium hydride species should be formed in situ from the reaction of Pd(PPh3)4, Xantphos, and PTSA. Next, alkynes 2a coordinate to the metal center from Int 1, which is followed by regioselective insertion into alkyne 2a, and affords the alkenylpalladium intermediate (E)-Int 2, which can be converted into (Z)-Int 2’ though isomerization in the catalytic system of Pd–H. however, the formation of (E)-Int 2 is more inclined with bulky steric hindered ligand (Xantphos). Then the coordination and insertion of CO leads to acylpalladium complex Int 3 as the key intermediate. Finally, alcoholysis of acylpalladium complex Int 3 leads to the desired α, β-unsaturated succinate 3aa and regenerate the active L-Pd-H specie for the next catalytic cycle.

      3. Conclusion

      In summary, a high regio- and stereoselective alkoxycarbonylation of unsymmetrical internal alkynes with alcohols or phenols enabled by palladium catalysis has been developed. A series of α, β-unsaturated succinates with a broad range of functional groups tolerance were obtained in exclusive (E)-stereoselectivity and mild reaction conditions (40 ​°C, 1 ​bar of CO). Furthermore, (Z)-stereoselectivity α, β-unsaturated can be obtained by a simple photocatalytic isomerization reaction.

      Data availability

      Data will be made available on request.

      Declaration of competing interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      Acknowledgments

      We thank the financial supports from DICP and K. C. Wong Education Foundation (GJTD-2020-08).

      Appendix A. Supplementary data

      The following is the Supplementary data to this article:

      References

        • Quintero-Duque S.
        • Dyballa K.M.
        • Fleischer I.
        Metal-catalyzed carbonylation of alkynes: key aspects and recent development.
        Tetrahedron Lett. 2015; 56: 2634-2650
        • Wu X.-F.
        Palladium-catalyzed carbonylative transformation of aryl chlorides and aryl tosylates.
        RSC Adv. 2016; 6: 83831-83837
        • Peng J.-B.
        • Geng H.-Q.
        • Wu X.-F.
        The Chemistry of CO: Carbonylation.
        Chem. 2019; 5: 526-552
        • Peng J.-B.
        • Wu F.-P.
        • Wu X.-F.
        First-row transition-metal-catalyzed carbonylative transformations of carbon electrophiles.
        Chem. Rev. 2019; 119: 2090-2127
        • Yin Z.
        • Xu J.-X.
        • Wu X.-F.
        No making without breaking: nitrogen-centered carbonylation reactions.
        ACS Catal. 2020; 10: 6510-6653
        • Liu Y.
        • Chen Y.-H.
        • Yi H.
        • Lei A.
        An update on oxidative C–H carbonylation with CO.
        ACS Catal. 2022; 12: 7470-7485
        • Zhang S.
        • Neumann H.
        • Beller M.
        Synthesis of α,β-unsaturated carbonyl compounds by carbonylation reactions.
        Chem. Soc. Rev. 2020; 49: 3187-3210
        • Sang R.
        • Hu Y.
        • Razzaq R.
        • Jackstell R.
        • Franke R.
        • Beller M.
        State-of-the-art palladium-catalyzed alkoxycarbonylations.
        Org. Chem. Front. 2021; 8: 799-811
        • Kiss G.
        Palladium-catalyzed reppe carbonylation.
        Chem. Rev. 2001; 101: 3435-3456
        • Brennführer A.
        • Neumann H.
        • Beller M.
        Palladium-catalyzed carbonylation reactions of alkenes and alkynes.
        ChemCatChem. 2009; 1: 28-41
        • Boddien A.
        • Gärtner F.
        • Federsel C.
        • Piras I.
        • Junge H.
        • Jackstell R.
        • Beller M.
        • Laurenczy G.
        • Shi M.
        J. 2012; : 658-722
        • Wu X.-F.
        • Fang X.
        • Wu L.
        • Jackstell R.
        • Neumann H.
        • Beller M.
        Transition-metal-catalyzed carbonylation reactions of olefins and alkynes: a personal account.
        Acc. Chem. Res. 2014; 47: 1041-1053
        • James D.E.
        • Hines L.F.
        • Stille J.K.
        The palladium(II) catalyzed olefin carbonylation reaction. The stereochemistry of methoxypalladation.
        J. Am. Chem. Soc. 1976; 98: 1806-1809
        • Pennequin P.
        • Fontaine M.
        • Castanet Y.
        • Mortreux A.
        • Petit F.
        Palladium catalyzed oxidative carbonylation of alkenes by methyl formate.
        Appl. Catal. A-Gen. 1996; 135: 329-339
        • Drent E.
        • Arnoldy P.
        • Budzelaar P.H.M.
        Efficient palladium catalysts for the carbonylation of alkynes.
        J. Organomet. Chem. 1993; 455: 247-253
        • Oberhauser W.
        • Ienco A.
        • Vizza F.
        • Trettenbrein B.
        • Oberhuber D.
        • Strabler C.
        • Ortner T.
        • Brüggeller P.
        Regioselective hydromethoxycarbonylation of terminal alkynes catalyzed by palladium(II)–Tetraphos complexes.
        Organometallics. 2012; 31: 4832-4837
        • Crawford L.E.
        • Cole-Hamilton D.J.
        • Drent E.
        • Bühl M.
        Mechanism of alkyne alkoxycarbonylation at a Pd catalyst with P,N hemilabile ligands: a density functional study.
        Chem. Eur J. 2014; 20: 13923-13926
        • Queirolo M.
        • Vezzani A.
        • Mancuso R.
        • Gabriele B.
        • Costa M.
        • Della Ca’ N.
        Neutral vs anionic palladium iodide-catalyzed carbonylation of terminal arylacetylenes.
        J. Mol. Catal. Chem. 2015; 398: 115-126
        • Chen X.
        • Zhu H.
        • Wang W.
        • Du H.
        • Wang T.
        • Yan L.
        • Hu X.
        • Ding Y.
        Multifunctional single-site catalysts for alkoxycarbonylation of terminal alkynes.
        ChemSusChem. 2016; 9: 2451-2459
        • Qi H.
        • Huang Z.
        • Wang M.
        • Yang P.
        • Du C.-X.
        • Chen S.-W.
        • Li Y.
        Bifunctional ligands for Pd-catalyzed selective alkoxycarbonylation of alkynes.
        J. Catal. 2018; 363: 63-68
        • Yang D.
        • Liu L.
        • Wang D.-L.
        • Lu Y.
        • Zhao X.-L.
        • Liu Y.
        Novel multi-dentate phosphines for Pd-catalyzed alkoxycarbonylation of alkynes promoted by H2O additive.
        J. Catal. 2019; 371: 236-244
        • Liu D.
        • Ke M.
        • Ru T.
        • Ning Y.
        • Chen F.-E.
        Room-temperature Pd-catalyzed methoxycarbonylation of terminal alkynes with high branched selectivity enabled by bisphosphine-picolinamide ligand.
        Chem. Commun. 2022; 58: 1041-1044
        • Zhao K.-C.
        • Liu L.
        • Chen X.-C.
        • Yao Y.-Q.
        • Guo L.
        • Lu Y.
        • Zhao X.-L.
        • Liu Y.
        Multiple-functional diphosphines: synthesis, characterization, and application to Pd-catalyzed alkoxycarbonylation of alkynes.
        Organometallics. 2022; 41: 750-760
        • Knifton J.F.
        α,β-unsaturated carboxylic esters from alkynes catalyzed by homogeneous palladium complexes.
        J. Mol. Catal. 1977; 2: 293-299
        • El Ali B.
        • Alper H.
        Synthesis of unsaturated esters, including t-alkyl esters, by the palladium-catalyzed carbonylation of alkynes in the presence of alcohols and 1,4-bis(diphenylphosphino)butane.
        J. Mol. Catal. 1991; 67: 29-33
        • Akao M.
        • Sugawara S.
        • Amino K.
        • Inoue Y.
        Regioselective hydroesterification of 1-alkynes catalyzed by palladium–phosphine complexes.
        J. Mol. Catal. Chem. 2000; 157: 117-122
        • Núñez Magro A.A.
        • Robb L.-M.
        • Pogorzelec P.J.
        • Slawin A.M.Z.
        • Eastham G.R.
        • Cole-Hamilton D.J.
        Highly selective formation of unsaturated esters or cascade reactions to α,ω-diesters by the methoxycarbonylation of alkynes catalysed by palladium complexes of 1,2-bis(ditertbutylphosphinomethyl)benzene.
        Chem. Sci. 2010; 1: 723-730
      1. (a)
        • Chen X.
        • Zhu H.
        • Wang T.
        • Li C.
        • Yan L.
        • Jiang M.
        • Liu J.
        • Sun X.
        • Jiang Z.
        • Ding Y.
        The 2V-P,N polymer supported palladium catalyst for methoxycarbonylation of acetylene.
        J. Mol. Catal. Chem. 2016; 414: 37-46
      2. (b)
        • Yang J.
        • Kong D.
        • Wu H.
        • Shen Z.
        • Zou H.
        • Zhao W.
        • Huang G.
        Palladium-catalyzed regio- and chemoselective double-alkoxycarbonylation of 1,3-diynes: a computational study.
        Org. Chem. Front. 2022; 9: 2697-2707
        • Liu J.
        • Yang J.
        • Baumann W.
        • Jackstell R.
        • Beller M.
        Stereoselective synthesis of highly substituted conjugated dienes via Pd-catalyzed carbonylation of 1,3-diynes.
        Angew. Chem. Int. Ed. 2019; 58: 10683-10687
        • Kuai C.-S.
        • Xu J.-X.
        • Chen B.
        • Wu X.-F.
        Palladium-catalyzed regio- and stereoselective hydroaminocarbonylation of unsymmetrical internal alkynes toward α,β-unsaturated amides.
        Org. Lett. 2022; 24: 4464-4469
        • Kuniyasu H.
        • Yoshizawa T.
        • Kambe N.
        Palladium-catalyzed hydrophenoxycarbonylation of internal alkynes by phenol and CO: the use of Zn for the formation of active catalyst.
        Tetrahedron Lett. 2010; 51: 6818-6821
        • Yamaguchi T.
        • Yanagi T.
        • Hokari H.
        • Mukaiyama Y.
        • Kamijo T.
        • Yamamoto I.
        Preparation of optically active succinic acid derivatives. I. Optical resolution of 2-Benzyl-3-(cis-hexahydroisoindolin-2-ylcarbonyl)-propionic acid.
        Chem. Pharm. Bull. 1997; 45: 1518-1520
        • Whittaker M.
        • Floyd C.D.
        • Brown P.
        • Gearing A.J.H.
        Design and therapeutic application of matrix metalloproteinase inhibitors.
        Chem. Rev. 1999; 99: 2735-2776
        • Marcq V.
        • Mirand C.
        • Decarme M.
        • Emonard H.
        • Hornebeck W.
        MMPs inhibitors: new succinylhydroxamates with selective inhibition of MMP-2 over MMP-3, Bioorg.
        Med. Chem. Lett. 2003; 13: 2843-2846
        • Liu J.
        • Yang Y.
        • Ji R.
        An effective and convenient method for the preparation of KAD-1229.
        Helv. Chim. Acta. 2004; 87: 1935-1939
        • Carnahan M.A.
        • Grinstaff M.W.
        Synthesis of generational polyester dendrimers derived from glycerol and succinic or adipic acid.
        Macromolecules. 2006; 39: 609-616
      3. Global biosuccinic acid market to reach market volume of 710 kilotonnes by 2020: allied Market Research.
        Focus Powder Coating. 2014; (2014): 8
        • James D.E.
        • Stille J.K.
        The palladium(II) catalyzed olefin carbonylation reaction. Mechanisms and synthetic utility.
        J. Am. Chem. Soc. 1976; 98: 1810-1823
        • Gabriele B.
        • Salerno G.
        • Costa M.
        • Chiusoli G.P.
        Combined oxidative and reductive carbonylation of terminal alkynes with palladium iodide-thiourea catalysts.
        J. Organomet. Chem. 1995; 503: 21-28
        • Inoue S.
        • Yokota K.
        • Tatamidani H.
        • Fukumoto Y.
        • Chatani N.
        Chelation-assisted transformation: synthesis of 1,4-dicarboxylate esters by the Rh-catalyzed carbonylation of internal alkynes with pyridin-2-ylmethanol.
        Org. Lett. 2006; 8: 2519-2522
        • Huang Q.
        • Hua R.
        An efficient rhodium-catalyzed double hydroaminocarbonylation of alkynes with carbon monoxide and amines affording 1,4-diamide derivatives.
        Adv. Synth. Catal. 2007; 349: 849-852
        • Driller K.M.
        • Klein H.
        • Jackstell R.
        • Beller M.
        Iron-catalyzed carbonylation: selective and efficient synthesis of succinimides.
        Angew. Chem. Int. Ed. 2009; 48: 6041-6044
        • Gao Y.-X.
        • Chang L.
        • Shi H.
        • Liang B.
        • Wongkhan K.
        • Chaiyaveij D.
        • Batsanov A.S.
        • Marder T.B.
        • Li C.-C.
        • Yang Z.
        • Huang Y.
        A thiourea-oxazoline library with axial chirality: ligand synthesis and studies of the palladium-catalyzed enantioselective bis(methoxycarbonylation) of terminal olefins.
        Adv. Synth. Catal. 2010; 352: 1955-1966
        • Liu H.
        • Lau G.P.S.
        • Dyson P.J.
        Palladium-catalyzed aminocarbonylation of alkynes to succinimides.
        J. Org. Chem. 2015; 80: 386-391
        • Liu J.
        • Dong K.
        • Franke R.
        • Neumann H.
        • Jackstell R.
        • Beller M.
        Selective palladium-catalyzed carbonylation of alkynes: an atom-economic synthesis of 1,4-dicarboxylic acid diesters.
        J. Am. Chem. Soc. 2018; 140: 10282-10288
        • Yang D.
        • Liu H.
        • Wang D.-L.
        • Luo Z.
        • Lu Y.
        • Xia F.
        • Liu Y.
        Co-catalysis over a bi-functional ligand-based Pd-catalyst for tandem bis-alkoxycarbonylation of terminal alkynes.
        Green Chem. 2018; 20: 2588-2595
        • Guo W.-D.
        • Liu L.
        • Yang S.-Q.
        • Chen X.-C.
        • Lu Y.
        • Vo-Thanh G.
        • Liu Y.
        Synergetic catalysis for one-pot bis-alkoxycarbonylation of terminal alkynes over Pd/Xantphos−Al(OTf)3 Bi-functional catalytic system.
        ChemCatChem. 2020; 12: 1376-1384
        • Zhu L.
        • Liu L.-J.
        • Jiang Y.-Y.
        • Liu P.
        • Fan X.
        • Zhang Q.
        • Zhao Y.
        • Bi S.
        Mechanism and origin of ligand-controlled chemo- and regioselectivities in palladium-catalyzed methoxycarbonylation of alkynes.
        J. Org. Chem. 2020; 85: 7136-7151
        • Li X.
        • Feng S.
        • Hemberger P.
        • Bodi A.
        • Song X.
        • Yuan Q.
        • Mu J.
        • Li B.
        • Jiang Z.
        • Ding Y.
        Iodide-coordinated single-site Pd catalysts for alkyne dialkoxycarbonylation.
        ACS Catal. 2021; 11: 9242-9251
        • Ji X.
        • Shen C.
        • Tian X.
        • Zhang H.
        • Ren X.
        • Dong K.
        Asymmetric double hydroxycarbonylation of alkynes to chiral succinic acids enabled by palladium relay catalysis.
        Angew. Chem. Int. Ed. 2022; 61e202204156
        • Singh A.
        • Fennell C.J.
        • Weaver J.D.
        Photocatalyst size controls electron and energy transfer: selectable E/Z isomer synthesis via C–F alkenylation.
        Chem. Sci. 2016; 7: 6796-6802
        • An X.-D.
        • Zhang H.
        • Xu Q.
        • Yu L.
        • Yu S.
        Stereodivergent synthesis of α-aminomethyl cinnamyl ethers via photoredox-catalyzed radical relay reaction.
        Chin. J. Chem. 2018; 36: 1147-1150
        • Zhang H.
        • Yu S.
        Visible light-promoted isomerization of alkenes.
        Chin. J. Org. Chem. 2019; 39: 95-108
        • Wang M.
        • He Y.-Q.
        • Zhu Y.
        • Song Z.-B.
        • Wang X.-Y.
        • Huang H.-Y.
        • Cao B.-P.
        • Tian W.-F.
        • Xiao Q.
        The wavelength-regulated stereodivergent synthesis of (Z)- and (E)-1,4-enediones from phosphonium ylides.
        Org. Chem. Front. 2021; 8: 5934-5940