Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2022 Sep 7.
Published in final edited form as: Org Chem Front. 2021 Jun 22;8(17):4805–4813. doi: 10.1039/d1qo00824b

Decarbonylative Sulfide Synthesis from Carboxylic Acids and Thioesters via Cross-Over C–S Activation and Acyl Capture

Chengwei Liu a,*, Michal Szostak a,*
PMCID: PMC8570612  NIHMSID: NIHMS1725032  PMID: 34745635

Abstract

A method for the synthesis of sulfides from carboxylic acids via thioester C–S activation and acyl capture has been accomplished, wherein thioesters serve as dual electrophilic activators to carboxylic acids as well as S-nucleophiles through the merger of decarbonylative palladium catalysis and sulfur coupling. This new concept engages readily available carboxylic acids as coupling partners to directly intercept sulfur reagents via redox-neutral thioester-enabled cross-over thioetherification. The scope of this platform is demonstrated in the highly selective decarbonylative thioetherification of a variety of carboxylic acids and thioesters, including late-stage derivatization of pharmaceuticals and natural products. This method operates under mild, external base-free, operationally-practical conditions, providing a powerful new framework to unlock aryl electrophiles from carboxylic acids and bolster the reactivity by employing common building blocks in organic synthesis.

Introduction

Sulfides represent one of the most fundamental moieties in all areas of chemistry and are of immense importance in pharmaceutical development (Figure 1).1 Thus, new methods for the synthesis of sulfides are receiving increasing attention. Typical methods are centered on the synthesis of sulfides by alkylation of thiols,2a addition of organometallics to disulfides,2b hydrothiolation reactions,2c and Pummerer rearrangements.2d With the advent of transition-metal-catalyzed cross-coupling reactions, a variety of C–S coupling protocols for the synthesis of thioethers from aryl halides or pseudohalides have emerged as an increasingly powerful strategy for the synthesis of thioethers.3 Further recent progress in the synthesis of thioethers involves thioetherification of amides4,5 and esters6 by a decarbonylative pathway. However, thioether synthesis from amides or esters is challenging since reductants, such as magnesium or manganese, are required for these transformations. In this context, intramolecular C(O)–S decarbonylation of thioesters by CO de-insertion represents one of the most direct and useful fragment couplings for the synthesis of thioethers.7

Figure 1.

Figure 1.

Open in a new tab

Commercial pharmaceuticals containing thioethers.

In this framework, thioesters have emerged as highly valuable building blocks in organic synthesis, while acetyl-CoA has long been established as the key acyl transfer reagent in enzymatic pathways.8–10 Considering their high air- and moisture-stability, thioesters are well-tolerant to the chromatographic purification and significantly easier to handle than the corresponding acyl halides, while maintaining high electrophilic character of the C(O)–S group.9 Thus, thioesters have been widely used in chemical synthesis. In this context, transition-metal-catalyzed cross-coupling of thioesters has been well-established, and this manifold typically operates via acyl-type coupling with the –SR moiety serving as a leaving group. Thus, substitution of the sulfur group with various nucleophiles has been widely studied, including Grignard reagents,11 organozinc reagents,12 boronic acids,13 alcohols,14 amines,15 hydrides,16 silanes17 and alkynes.18 In sharp contrast to the use of thioesters as C(O)–S electrophiles, the function of thioesters as nucleophiles to react with electrophiles has been rarely developed (Figure 2A).19

Figure 2.

Figure 2.

Open in a new tab

Acyl capture catalysis for the synthesis of sulfides via decarbonylative cross-over C–S bond activation.

Although transition-metal-catalyzed thiolation of halides and pseudohalides with thiols is a fundamental method for the synthesis of thioethers, these protocols are inherently limited due to the formation of RS–M–H intermediates from free thiols, thus requiring the use of a base and leading to the generation of reduction by-products (Figure 2B). Thus, the development of new “protonless” sulfur reagents is highly desirable.

Simultaneously, we recognized that carboxylic acids are fundamental building blocks in organic synthesis.20,21 Transition-metal-catalyzed cross-coupling of carboxylic acids is highly attractive due to their pervasiveness as crystalline starting materials across various faces of chemical science.22–24 Recently, compelling applications of cross-coupling of carboxylic acids by decarboxylative and decarbonylative mechanisms to form C–C and C–X bonds in a highly selective fashion have appeared.25–31

Our interest in the cross-coupling chemistry of carboxylic acid functional groups led us to take advantage of the dual reactivity of thioesters as cross-over C(O)–S nucleophiles to achieve the synthesis of sulfides via versatile acyl capture catalysis platform (Figure 2C). Further, given the widespread availability and the tremendous potential of carboxylic acids as unconventional cross-coupling electrophiles, we envisioned the simultaneous activation of a carboxylic acid moiety to provide a new general approach to the synthesis of thioesters from carboxylic acids and thioesters by acyl capture.

The proposed mechanism for this general strategy involves reversible carboxylic acid coupling with an acyl activator from thioester to form an active carboxylic acid (i.e. mixed anhydride) in situ by acyl capture exploiting the high reactivity of the C(O)–S carbonyl group, followed by oxidative addition of the C(acyl)–O bond to a transition-metal, decarbonylation, ligand exchange and reductive elimination, which results in engaging of carboxylic acids in a modular decarbonylative cross-coupling platform (Figure 2D). This strategy forges carbon–sulfur bonds via the classical oxidative addition mechanism operating under redox-neutral conditions in the absence of external bases and provides a general solution to the routine application of carboxylic acids for the synthesis of valuable sulfides with high chemoselectivity and excellent functional group tolerance. It should be noted that two pathways are possible in Figure 2D for the cleavage of the C–O bond in a mixed anhydride (path a and b). We hypothesized that given the thermodynamic nature of the process and the transient stability of acyl-metal complexes, one thioether product would be formed predominantly (path a) (vide infra). We further proposed that the mechanism for the formation of the mixed anhydride would involve metal-free acylation.

The following features of our study are noteworthy: (1) the first palladium-catalyzed decarbonylative thioetherification of carboxylic acids and related derivatives; (2) acyl capture catalysis that in principle is broadly applicable to exploiting carboxylic acids in a wide array of transition-metal-catalyzed cross-coupling protocols; (3) the first cross-over S-transfer from thioesters to carboxylic acids; (4) the use of mild “protonless” S-nucleophiles; (5) external-base-free and reductant-free conditions; (6) broad scope and applications to late-stage functionalization exploiting the ubiquity of carboxylic acid functional group.

Results and Discussion

The proposed acyl capture catalysis was first investigated using 2-naphthoic acid (1a) and S-phenyl benzothioate (2a) (1a:2a, 1:1 ratio) as model substrates (see SI). To our delight, after extensive optimization we identified the catalyst system consisting of Pd(OAc)2 (5 mol%) and dppp (10 mol%) (dppp = 1,3-bis(diphenylphosphino)propane) in toluene at 160 °C as the optimum combination to deliver the desired sulfide product (3a) in quantitative yield.

A summary of key optimization results is presented in the SI. Several points are worth noting: (1) other phosphane ligands can be used, such as dppm (81%), dppe (82%), dppb (63%), dpppent (30%), dppf (73%), Xantphos (65%), however, bidentate phosphines are preferred cf. PCy3 (<2%), PPh3 (<2%); (2) the coupling ensues at temperatures as low as 120 °C, consistent with the efficient decarbonylation step (48% yield); (3) monitoring of the reaction indicates 75% conversion after 60 min, consistent with facile coupling. It should be noted that the carboxylic acid is activated in the absence of external-bases and additional external-activators, while the thioester provides an “internal” cross-over activator and offers nucleophilic sulfur to deliver the desired coupling product. Toluene is the preferred solvent for the reaction. Furthermore, dioxane is typically also a preferred solvent for decarbonylative couplings, while lower efficiency is observed in higher boiling solvents.

Considering that thioesters serve as the dual component in this transformation, we first explored the effect of thioester acyl and S-substitution on the reaction (Figure 3A-B). As shown, the acyl part accommodates benzoyl, alkyl-benzoyl, aryl-benzoyl as well as vinyl substitution in good to excellent yields, while modest yield is obtained with methoxy and electron-withdrawing substitution (Figure 3A). Thus, S-phenyl benzothioate (2a) emerges as the most reactive among a range of acyl functionalized thioesters. Furthermore, the scope of the S-substitution was investigated (Figure 3B). As shown, electron-neutral (2a), electron-rich (2h), fluoro-containing (2i), sterically-hindered (2j) and even alkyl (2k) thioesters delivered to desired products in excellent yields. The electron-deficient thioester (2l) gave a promising but lower efficiency due to the electronic mismatch with the acyl capture and ligand exchange steps. We note that only one product was generally observed in the coupling, selectivity >90:10 in all cases examined. We believe that the selectivity in Figure 3A is connected to the acylation/decarbonylation selectivity, which results in the optimum performance of electronically-unbiased substrates, while in general electron-rich S-substituents are preferred over electron-deficient S-substituents (Figure 3B). An alternative mechanism might involve dehydration to symmetrical anhydride. Homo anhydrides have not been observed under the reaction conditions.

Figure 3.

Figure 3.

Open in a new tab

Acyl capture catalysis for the synthesis of sulfides via decarbonylative cross-over C–S bond activation. Conditions: 1 (1.0 equiv), 2 (1.0 equiv), Pd(OAc)2 (5 mol%), dppp (10 mol%), toluene (0.25 M), 160 °C, 15 h. See SI for details.

We next turned our attention to investigate the scope of the carboxylic acid component amenable to this transformation (Figure 3C). As shown, the method is compatible with a remarkably broad range of electronically- and sterically-functionalized carboxylic acids, attesting to its generic format. As shown, various electron-neutral (3a, 3g, 3h, 3s), electron-rich (3k) and electron-deficient (3i) carboxylic acids can be employed to deliver the desired products in good to excellent yields. We believe that in case of 3h the reaction follows the proposed mechanism since decarbonylation of 2 is slower than acylation to form a mixed anhydride. Importantly, medicinally-privileged motifs, such as trifluoromethyl ethers (3j), as well as functional handles, such as tosyl (3l), nitrile (3m), esters (3n, 3t, 3ad), ketones (3o, 3u), aldehydes (3p), halides (3q, 3r) are well compatible. It is noteworthy that steric hinderance (3v-x) can be readily employed. Pleasingly, heterocycles, such as quinoline and pyridine (3y-z) are well-tolerated. Furthermore, cinnamic acids (3aa-ac) are also compatible in this transformation, providing vinyl sulfides. Overall, these results highlight the broad scope of carboxylic acids that can be employed in this redox-neutral decarbonylative coupling.

It is noteworthy that this protocol permits direct late-stage derivatization of pharmaceuticals, such as antihyperuricemics (Probenecid, 3ae), retinoids (Adapalene, 3af), antineoplastic agents (Bexarotene, 3ag) and natural products (Tocopherol, 3ah). This late-stage cross-coupling is feasible due to the innate presence of the carboxylic acid moiety; thus, the cross-coupling approach exploiting carboxylic acids as electrophiles through redox-neutral decarbonylation offers powerful alternative to the traditional cross-coupling of halides or pseudohalides and, as shown, may be readily applied to the late-stage thiolation.

Intrigued by the efficiency of this robust acyl capture catalysis, we sought to gain insight into the reaction mechanism of this process:

  1. To gain insight into the acyl capture step of the activator, we conducted the model reaction in the absence of Pd-catalyst (Figure 4A). The reaction resulted in the exchanged thioester (2p) in 25% yield, recovered thioester (2a) in 72% yield and sulfide (3a) in less than 2% yield. This finding suggests that a mixed anhydride reacts with SPh anion to form 2p, which is the intermediate in this process. Typically, we did not observe homo anhydrides under these conditions.

  2. To investigate different activators, various C–S reagents were prepared and subjected to the standard reaction conditions (Figure 4B). As such, both S-phenyl benzothioate (2a) and S-phenyl ethanethioate (2m) delivered the desired product, albeit the latter was less effective, affording the coupling product in 38% yield. In contrast, less electrophilic S-thiocarbamate (2n) was unreactive under the reaction conditions, consistent with the relative nS→π*C=O delocalization in the C(acyl)-S group.

  3. To evaluate the chemoselectivity of this activation method with respect to the classical electrophiles, we have applied a range of electrophiles to the standard reaction conditions (Figure 4C), such as aryl bromide (1af), aryl sulfonate (1ag) and aryl pivalate (1ah), which resulted in unproductive reactions and recovery of starting materials, highlighting the selectivity and unique complementarity of the method.

  4. To gain insight into the observed selectivity, we performed a range of intermolecular competition experiments (Figure 4D-E). Thus, competition experiments between different carboxylic acids revealed that electron-deficient substrates are inherently more reactive that their electron-rich counterparts (4-CF3:4-MeO = 83:17), while sterically-hindered carboxylic acids showed similar reactivity to ortho-unsubstituted acids (2-Me:2-H = 50:50) and polycyclic aromatic acids showed comparable reactivity to benzoic acid (2-Np:Ph = 69:31) (Figure 4D). Interestingly, electron-deficient substrates are inherently more reactive than electron-rich counterparts, consistent with the ease of acyl capture and decarbonylation. Furthermore, S-aryl electron-deficient thioesters are inherently more reactive than their electron-rich counterparts (4-CF3:4-MeO = 89:11), while sterically-hindered thioesters are more reactive than their ortho-unsubstituted counterparts (2-Me:H = 70:30) and aromatic thioesters are more reactive than alkyl substrates (Ph:n-C10H21 = 56:44) (Figure 4E). At this stage, longer chain S-alky thiol has been used as representative to probe for β-hydride elimination/olefin migration (cf. Me, Et), which has not been detected under the reaction conditions. Overall, the observed effects give insight into the selectivity of the process and are a net result of acylation and decarbonylation steps.

Figure 4.

Figure 4.

Open in a new tab

Acyl capture catalysis for the synthesis of sulfides via decarbonylative cross-over C–S bond activation. See SI for details.

Finally, in order to further demonstrate the selectivity and synthetic utility of this novel reaction manifold, we performed a series of sequential transformations (Figure 4F-G). Thus, “traceless” toluene oxidation merged with acyl capture catalysis delivered a 4-biphenyl-thioether in excellent yield, illustrating the use of hydrocarbons as carboxylic acid precursors (Figure 4F). Furthermore, “classical” Ar–Br cross-coupling merged with “decarbonylative” Ar–CO2H cross-coupling furnished a 2-biphenyl thioether in high yield, emphasizing the synthetic utility of the complementary cross-coupling manifolds (Figure 4G).

Conclusions

In conclusion, we have shown, for the first time, that acyl capture catalysis can be utilized for the direct decarbonylative base-free thioetherification of carboxylic acids using thioesters as thiolating reagents without external activators. Compared with the traditional pathway, thioesters serve as dual electrophilic activators to carboxylic acids as well as S-nucleophiles through the merger of decarbonylative palladium catalysis and sulfur coupling. The protocol exemplifies the utility of cross-over redox-neutral decarbonylative catalysis to accomplish highly selective thioetherification of a variety of carboxylic acids and thioesters, which represent some of the most pervasive building blocks in chemical science. We fully expect that activation of carboxylic acids with cross-over electrophiles will lead to new cross-coupling concepts in transition-metal-catalysis.

Supplementary Material

supp

Acknowledgements

We thank the NIH (1R35GM133326), the NSF (CAREER CHE-1650766) and Rutgers University for generous financial support. The Bruker 500 MHz spectrometer used in this study was supported by the NSF-MRI (CHE-1229030). Additional support was provided by the Rutgers Graduate School in the form of Dean’s Dissertation Fellowship. We thank Mr. Tongliang Zhou (Rutgers University) for helpful discussions.

Footnotes

Conflicts of interest

There are no conflicts to declare.

Electronic Supplementary Information (ESI) available: [details of any supplementary information available should be included here]. See DOI: 10.1039/D1QO00824B

References

  • 1.(a) For leading reviews sulfur-containing drugs, see: Ilardi EA, Vitaku E and Njardarson JT, Data-Mining for Sulfur and Fluorine: An Evaluation of Pharmaceuticals To Reveal Opportunities for Drug Design and Discovery, J. Med. Chem. 2014, 57, 2832–2842; [DOI] [PubMed] [Google Scholar]; (b) Feng M, Tang B, Liang SH, Jiang X, Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry, Curr. Top. Med. Chem, 2016, 16, 1200–1216; [DOI] [PMC free article] [PubMed] [Google Scholar]; (c) Beno BR, Yeung KS, Bartberger MD, Pennington LD, Meanwell NA. A Survey of the Role of Noncovalent Sulfur Interactions in Drug Design, J. Med. Chem. 2015, 58, 4383–4438; [DOI] [PubMed] [Google Scholar]; (d) Scott KA, Njardarson JT, Analysis of US FDA-Approved Drugs Containing Sulfur Atoms, Top Curr. Chem. 2018, 376(5), 1–34. [DOI] [PubMed] [Google Scholar]; (e) For recent studies on the synthesis of sulfur heterocycles, see: Lamers P, Buglioni L, Koschmieder S, Chatain N, Bolm C, Benzo[c]isothiazole 2-Oxides: Three-Dimensional Heterocycles with Cross-Coupling and Functionalization Potential, Adv. Synth. Catal. 2016, 358, 3649–3653; [Google Scholar]; (f) Lamers P, Bolm C, Tetrahydrobenzo[c]thieno[2,1-e]isothiazole 4-Oxides: Three-Dimensional Heterocycles as Cross-Coupling Building Blocks, Org. Lett. 2018, 20, 116–118; [DOI] [PubMed] [Google Scholar]; (g) Yu H, Li Z, Bolm C, Three-Dimensional Heterocycles by Iron-Catalyzed Ring-Closing Sulfoxide Imidation, Angew. Chem. Int. Ed. 2018, 57, 12053–12056; [DOI] [PubMed] [Google Scholar]; (h) De Oliveira Silva A, McQuade J, Szostak M, Recent Advances in the Synthesis and Reactivity of Isothiazoles, Adv. Synth. Catal. 2019, 361, 3050–3067. [Google Scholar]
  • 2 (a).Landini D, Rolla F, Org. Synth. 1978, 58, 143–144; [Google Scholar]; (b) Yus M, Martinez P, Guijarro D, Direct Transformation of Allylic and Benzylic Thiols, Thioethers, and Disulfides into Organolithium Compounds, Synth. Commun. 2003, 33, 2365–2376; [Google Scholar]; (c) Hoyle CE, Bowman CN, Thiol-Ene Click Chemistry, Angew. Chem. Int. Ed. 2010, 49, 1540–1573; [DOI] [PubMed] [Google Scholar]; (d) Lucchi O, Miotti U, Modena G, The Pummerer Reaction of Sulfinyl Compounds, Organic Reactions. 1991, 40, 157–184; [Google Scholar]; (e) For excellent examples of synthesis and application of thioesters see: Wang M, Dai Z, Jiang X, Design and Application of α-Ketothioesters as 1,2-Dicarbonyl-forming Reagents, Nat. Commun. 2019, 10, 2661, 1–9; [DOI] [PMC free article] [PubMed] [Google Scholar]; (f) For a divergent synthesis of thioethers and thioesters from sulfothioate and organosilicon compounds, see Qiao Z, Jiang X , Ligand-Controlled Divergent Cross-Coupling Involving Organosilicon Compounds for Thioether and Thioester Synthesis, Org. Lett. 2016, 18, 1550–1553. [DOI] [PubMed] [Google Scholar]
  • 3.(a) For selected examples on the synthesis of thioethers, see: Jouffroy M, Kelly CB, Molander GA , Thioetherification via Photoredox/Nickel Dual Catalysis, Org. Lett. 2016, 18, 876–879; [DOI] [PMC free article] [PubMed] [Google Scholar]; (b) Oderinde MS, Frenette M, Robbins DW, Aquila B, Johannes JW, Photoredox Mediated Nickel Catalyzed Cross-Coupling of Thiols With Aryl and Heteroaryl Iodides via Thiyl Radicals, J. Am. Chem. Soc. 2016, 138, 1760–1763; [DOI] [PubMed] [Google Scholar]; (c) Liu B, Lim CH, Miyaka GM, Visible-Light-Promoted C–S Cross-Coupling via Intermolecular Charge Transfer, J. Am. Chem. Soc. 2017, 139, 13616–13619; [DOI] [PMC free article] [PubMed] [Google Scholar]; (d) Uyeda C, Tan Y, Fu GC, Peters JC, A New Family of Nucleophiles for Photoinduced, Copper-Catalyzed Cross-Couplings via Single-Electron Transfer: Reactions of Thiols with Aryl Halides Under Mild Conditions (0 °C), J. Am. Chem. Soc. 2013, 135, 9548–9552; [DOI] [PubMed] [Google Scholar]; (e) Fernández-Rodríguez MA, Shen Q, Hartwig JF, A General and Long-Lived Catalyst for the Palladium-Catalyzed Coupling of Aryl Halides with Thiols, J. Am. Chem. Soc. 2006, 128, 2180–2181; [DOI] [PubMed] [Google Scholar]; (f) Saravanan P, Anbarasan P, Palladium Catalyzed Aryl(alkyl)thiolation of Unactivated Arenes, Org. Lett. 2014, 16, 848–851; [DOI] [PubMed] [Google Scholar]; (g) Zhou J-Y, Tao S-W, Liu R-Q, Zhu Y-M, Forging C–S Bonds through Nickel-Catalyzed Aryl Anhydrides with Thiophenols: Decarbonylation or Decarbonylation Accompanied by Decarboxylation, J. Org. Chem. 2019, 84, 11891–11901; [DOI] [PubMed] [Google Scholar]; (h) Brigham CE, Malapit CA, Lalloo N, Sanford MS, Nickel-Catalyzed Decarbonylative Synthesis of Fluoroalkyl Thioethers, ACS Catal. 2020, 10, 8315–8320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.(a) For selected reviews on amide cross-coupling, see: Li G, Ma S, Szostak M, Amide Bond Activation: The Power of Resonance, Trends Chem. 2020, 2, 914–928; [Google Scholar]; (b) Kaiser D, Bauer A, Lemmerer M, Maulide N, Amide Activation: An Emerging Tool for Chemoselective Synthesis, Chem. Soc. Rev. 2018, 47, 7899–7925; [DOI] [PubMed] [Google Scholar]; (c) Dander JE, Garg NK, Breaking Amides using Nickel Catalysis, ACS Catal. 2017, 7, 1413–1423; [DOI] [PMC free article] [PubMed] [Google Scholar]; (d) Liu C, Szostak M, Twisted Amides: From Obscurity to Broadly Useful Transition-Metal-Catalyzed Reactions by N−C Amide Bond Activation, Chem. Eur. J. 2017, 23, 7157–7173. [DOI] [PubMed] [Google Scholar]
  • 5.(a) For representative decarbonylative coupling of amides, see: Meng G, Szostak M, General Olefin Synthesis by the Palladium-Catalyzed Heck Reaction of Amides: Sterically Controlled Chemoselective N–C Activation, Angew. Chem. Int. Ed. 2015, 54, 14518–14522; [DOI] [PubMed] [Google Scholar]; (b) Shi S, Meng G, Szostak M, Synthesis of Biaryls through Nickel-Catalyzed Suzuki-Miyaura Coupling of Amides by Carbon–Nitrogen Bond Cleavage, Angew. Chem. Int. Ed. 2016, 55, 6959–6963; [DOI] [PubMed] [Google Scholar]; (c) Liu C, Szostak M, Decarbonylative Phosphorylation of Amides by Palladium and Nickel Catalysis: The Hirao Cross-Coupling of Amide Derivatives, Angew. Chem. Int. Ed. 2017, 56, 12718–12722; [DOI] [PubMed] [Google Scholar]; (d) Ji CL, Hong X, Factors Controlling the Reactivity and Chemoselectivity of Resonance Destabilized Amides in Ni-Catalyzed Decarbonylative and Nondecarbonylative Suzuki-Miyaura Coupling, J. Am. Chem. Soc. 2017, 139, 15522–15529; [DOI] [PubMed] [Google Scholar]; (e) Lee SC, Liao H-H, Chatupheeraphat A, Rueping M, Nickel-Catalyzed C−S Bond Formation via Decarbonylative Thioetherification of Esters, Amides and Intramolecular Recombination Fragment Coupling of Thioesters, Chem. Eur. J. 2018, 24, 3608–3612. [DOI] [PubMed] [Google Scholar]
  • 6.For an excellent review on decarbonylative cross-coupling, see: Lu H, Yu TY, Xu PF, Wei H, Selective Decarbonylation via Transition-Metal-Catalyzed Carbon–Carbon Bond Cleavage, Chem. Rev. 2020, 120, 365–411, and references cited therein. [DOI] [PubMed] [Google Scholar]
  • 7.(a) For examples of intramolecular decarbonylation of thioesters, see: Liu C, Szostak M, Decarbonylative Thioetherification by Nickel Catalysis Using Air- and Moisture-stable Nickel Precatalysts, Chem. Commun. 2018, 54, 2130–2133; [DOI] [PubMed] [Google Scholar]; (b) Ichiishi N, Malapit CA, Wozniak L, Sanford MS, Palladium- and Nickel-Catalyzed Decarbonylative C−S Coupling to Convert Thioesters to Thioethers, Org. Lett. 2018, 20, 44–47; [DOI] [PMC free article] [PubMed] [Google Scholar]; (c) Osakada K, Yamamoto T, Yamamoto A, Decarbonylation of Thiol Esters to Give Sulfides Promoted by Transition Metal Complexes, Tetrahedron Lett. 1987, 28, 6321–6324; [Google Scholar]; (d) Kato T, Kuniyasu H, Kajiura T, Minami Y, Ohtaka A, Kinomoto M, Terao J, Kurosawa H, Kambe N, β-cis-SAr Effect” on Decarbonylation from α,β-Unsaturated Acyl and Aroyl Complexes, Chem. Commun. 2006, 868–870; [DOI] [PubMed] [Google Scholar]; (e) Cao H, Liu X, Bie F, Shi Y, Han Y, Yan P, Szostak M, Liu C, General and Practical Intramolecular Decarbonylative Coupling of Thioesters via Palladium Catalysis, Org. Chem. Front. 2021, 8, 1587–1592. [Google Scholar]
  • 8 (a).Wächtershäuser G, Groundworks for an Evolutionary Biochemistry: The Iron-Sulphur World, Prog. Biophys. Mol. Biol. 1992, 58, 85–201; [DOI] [PubMed] [Google Scholar]; (b) Bracher PJ, Snyder PW, Bohall BR, Whitesides GM, The Relative Rates of Thiol-Thioester Exchange and Hydrolysis for Alkyl and Aryl Thioalkanoates in Water, Orig. Life Evol. Biosph. 2011, 41, 399–412; [DOI] [PubMed] [Google Scholar]; (c) Chandru K, Gilbert A, Butch C, Aono M, Cleaves HJ, The Abiotic Chemistry of Thiolated Acetate Derivatives and the Origin of Life, Sci. Rep. 2016, 6(29883), 1–11; [DOI] [PMC free article] [PubMed] [Google Scholar]; (d) Jakubowski H, Aminoacyl-tRNA synthetases and the evolution of coded peptide synthesis: the Thioester World, FEBS Lett. 2016, 590, 469–481. [DOI] [PubMed] [Google Scholar]
  • 9.Burhardt MN, Ahlburg A, Skrydstrup T, Palladium-Catalyzed Thiocarbonylation of Aryl, Vinyl, and Benzyl Bromides, J. Org. Chem. 2014, 79, 11830–11840. [DOI] [PubMed] [Google Scholar]
  • 10.(a) For reviews on cross-coupling of thioesters, see: Hirschbeck V, Gehrtz PH, Fleischer I, Metal-Catalyzed Synthesis and Use of Thioesters: Recent Developments, Chem. Eur. J. 2018, 24, 7092–7107; [DOI] [PubMed] [Google Scholar]; (b) Wang L, He W, Yu Z, Transition-Metal Mediated Carbon-Sulfur Bond Activation and Transformations, Chem. Soc. Rev. 2013, 42, 599–621; [DOI] [PubMed] [Google Scholar]; (c) Beletskaya IP, Ananikov VP, Transition-Metal-Catalyzed C−S, C−Se, and C−Te Bond Formation via Cross-Coupling and Atom-Economic Addition Reactions, Chem. Rev. 2011, 111, 1596–1636; [DOI] [PubMed] [Google Scholar]; (d) Kuniyasu H, Kurosawa H, Transition-Metal-Catalyzed Carbon-Heteroatom Three-Component Cross-Coupling Reactions: A New Concept for Carbothiolation of Alkynes, Chem. Eur. J. 2002, 8, 2660–2665. [DOI] [PubMed] [Google Scholar]
  • 11.(a) For examples of cross-coupling of thioesters with Grignard reagents, see: Araki M, Sakata S, Takei H, Mukaiyama T , A Convenient Method for the Preparation of Ketones by the Reaction of Grignard Reagents with Carboxylic Acid Derivatives, Bull. Chem. Soc. Jpn. 1974, 47, 1777–1780; [Google Scholar]; (b) Cardellicchio C, Fiandanese V, Marchese G, Ronzini L, A Highly Efficient Synthetic Route to Ketones through Sequential Coupling Reactions of Grignard Reagents with S-Phenyl Carbonochloridothioate in the Presence of Nickel or Iron Catalysts, Tetraheron Lett. 1985, 26, 3595–3598. [Google Scholar]
  • 12.(a) For examples of cross-coupling of thioesters with organozinc reagents, see: Tokuyama H, Yokoshima S, Yamashita T, Fukuyama T, A Novel Ketone Synthesis by a Palladium-Catalyzed Reaction of Thiol Esters and Organozinc Reagents, Tetraheron Lett. 1998, 39, 3189–3192; [Google Scholar]; (b) Shimizu T, Seki M, Palladium on Charcoal-Catalyzed Fukuyama Coupling Reaction, Tetraheron Lett. 2001, 42, 429–432; [Google Scholar]; (c) Shimizu T, Seki M, A Novel Synthesis of Functionalized Ketones via a Nickel-Catalyzed Coupling Reaction of Zinc Reagents with Thiolesters, Tetraheron Lett. 2002, 43, 1039–1042; [Google Scholar]; (d) Kunchithapatham K, Eichman CC, Stambuli JP, Synthesis of Diaryl Ketones via a Phosphine-Free Fukuyama Reaction, Chem. Commun. 2011, 47, 12679–12681; [DOI] [PubMed] [Google Scholar]; (e) Lutter FH, Grokenberger L, Hofmayer MS and Knochel P, Cobalt-catalyzed acylation-reactions of (hetero)arylzinc pivalates with thiopyridyl ester derivatives, Chem. Sci, 2019, 10, 8241–8245; [DOI] [PMC free article] [PubMed] [Google Scholar]; (f) Gehrtz PH, Kathe P, Fleischer I, Nickel-Catalyzed Coupling of Arylzinc Halides with Thioesters, Chem. Eur. J, 2018, 24, 8774–8778; [DOI] [PubMed] [Google Scholar]; (g) Oost R, Misale A, Maulide N, Enantioconvergent Fukuyama Cross-Coupling of Racemic Benzylic Organozinc Reagents, Angew. Chem. Int. Ed, 2016, 55, 4587–4590. [DOI] [PubMed] [Google Scholar]
  • 13.(a) For examples of cross-coupling of thioesters with boronic acids, see: Liebeskind LS, Srogl J, Thiol Ester−Boronic Acid Coupling. A Mechanistically Unprecedented and General Ketone Synthesis, J. Am. Chem. Soc. 2000, 122, 11260–11261; [Google Scholar]; (b) Savarin C, Srogl J, Liebeskind LS, Thiol Ester−Boronic Acid Cross-Coupling. Catalysis Using Alkylative Activation of the Palladium Thiolate Intermediate, Org. Lett. 2000, 2, 3229–3231; [DOI] [PubMed] [Google Scholar]; (c) Yu Y, Liebeskind LS, Copper-Mediated, Palladium-Catalyzed Coupling of Thiol Esters with Aliphatic Organoboron Reagents, J. Org. Chem. 2004, 69, 3554–3557. [DOI] [PubMed] [Google Scholar]
  • 14.For esterification of thioesters, see: Os’kina IA, Vlasov VM, Activation Parameters of the Reactions of 4-Nitrophenyl Benzoates and S-Phenyl Benzothioate with 4-Chlorophenol in Dimethylformamide in the Presence of Potassium Carbonate, Russ. J. Org. Chem. 2009, 4, 523–527. [Google Scholar]
  • 15.For amidation of thioesters, see: Ueda M, Seki K, Imai Y, S- and N-Acyl Derivatives of 2-Mercaptobenzoxazole; New, Highly Reactive Acylating Agents for Synthesis of Amides and Esters, Synthesis 1981, 991–993. [Google Scholar]
  • 16.For reduction of thioesters, see: Fukuyama T, Lin S-C, Li L, Facile Reduction of Ethyl Thiol Esters to Aldehydes: Application to a Total Synthesis of (+)-Neothramycin A Methyl Ether, J. Am. Chem. Soc. 1990, 112, 7050–7051. [Google Scholar]
  • 17.For silylation of thioesters, see: Azuma H, Okano K, Tokuyama H, Synthesis of Acylsilanes by Palladium-catalyzed Cross-coupling Reaction of Thiol Esters and Silylzinc Chlorides, Chem. Lett. 2011, 40, 959–961. [Google Scholar]
  • 18.For cross-coupling of thioesters with alkynes, see: Mehta VP, Sharma A, Vander Eycken E, The First Palladium-Catalyzed Desulfitative Sonogashira-Type Cross-Coupling of (Hetero)aryl Thioethers with Terminal Alkynes, Org. Lett. 2008, 10, 1147–1150. [DOI] [PubMed] [Google Scholar]
  • 19.Ishitobi K, Muto K, Yamaguchi J , Pd-Catalyzed Alkenyl Thioether Synthesis from Thioesters and N-Tosylhydrazones, ACS Catal. 2019, 9, 11685–11690. [Google Scholar]
  • 20 (a).Gooßen LJ, Rodriguez N, Gooßen K, Carboxylic Acids as Substrates in Homogeneous Catalysis, Angew. Chem. Int. Ed. 2008, 47, 3100–3120; [DOI] [PubMed] [Google Scholar]; (b) Pichette Drapeau M, Gooßen LJ, Carboxylic Acids as Directing Groups for C−H Bond Functionalization, Chem. Eur. J. 2016, 22, 18654–18677. [DOI] [PubMed] [Google Scholar]
  • 21 (a).Patra T, Maiti D, Decarboxylation as the Key Step in C−C Bond-Forming Reactions, Chem. Eur. J. 2017, 23, 7382–7401; [DOI] [PubMed] [Google Scholar]; (b) Trost BM, Fleming I, Comprehensive Organic Synthesis, Pergamon Press, 1991. [Google Scholar]
  • 22 (a).Dzik W, Lange P, Gooßen L, Carboxylates as Sources of Carbon Nucleophiles and Electrophiles: Comparison of Decarboxylative and Decarbonylative Pathways, Chem. Sci. 2012, 3, 2671–2678; [Google Scholar]; (b) Rodriguez N, Gooßen L, Decarboxylative Coupling Reactions: a Modern Strategy for C–C-Bond Formation, Chem. Soc. Rev. 2011, 40, 5030–5048. [DOI] [PubMed] [Google Scholar]
  • 23 (a).de Meijere A, Bräse S, Oestreich M, Metal-Catalyzed Cross-Coupling Reactions and More, Wiley, 2014; [Google Scholar]; (b) Molander G, Wolfe JP, Larhed M, Science of Synthesis: Cross-Coupling and Heck-Type Reactions, Thieme, 2013. [Google Scholar]
  • 24.(a) For seminal studies, see: Gooßen LJ, Dong G, Levy LM, Synthesis of Biaryls via Catalytic Decarboxylative Coupling, Science 2006, 313, 662–664; [DOI] [PubMed] [Google Scholar]; (b) Gooßen LJ, Rodriguez N, Melzer B, Linder C, Deng G, Levy LM, Biaryl Synthesis via Pd-Catalyzed Decarboxylative Coupling of Aromatic Carboxylates with Aryl Halides, J. Am. Chem. Soc. 2007, 129, 4824–4833; [DOI] [PubMed] [Google Scholar]; For oxidative Heck cross-coupling, see: (c) Myers AG, Tanaka D, Mannion MR, Development of a Decarboxylative Palladation Reaction and Its Use in a Heck-type Olefination of Arene Carboxylates, J. Am. Chem. Soc. 2002, 124, 11250–11251; [DOI] [PubMed] [Google Scholar]; (d) For decarbonylative cross-coupling of anhydrides, see: O’Brien EM, Bercot EA, Rovis T , Decarbonylative Cross-Coupling of Cyclic Anhydrides:  Introducing Stereochemistry at an sp3 Carbon in the Cross-Coupling Event, J. Am. Chem. Soc. 2003, 125, 10498–10499; [DOI] [PubMed] [Google Scholar]; (e) Li M, Hoover JM, Aerobic Copper-Catalyzed Decarboxylative Thiolation, Chem. Commun. 2016, 52, 8733–8736. [DOI] [PubMed] [Google Scholar]
  • 25.(a) For selected recent examples of decarbonylative and decarboxylative cross-coupling reactions, see: Keaveney ST, Schoenebeck F, Palladium-Catalyzed Decarbonylative Trifluoromethylation of Acid Fluorides, Angew. Chem. Int. Ed. 2018, 57, 4073–4077; [DOI] [PMC free article] [PubMed] [Google Scholar]; (b) Chatupheeraphat A, Liao HH, Srimontree W, Guo L, Minenkov Y, Poater A, Cavallo L, Rueping M, Ligand-Controlled Chemoselective C(acyl)−O Bond vs C(aryl)−C Bond Activation of Aromatic Esters in Nickel Catalyzed C(sp2)−C(sp3) Cross-Couplings, J. Am. Chem. Soc. 2018, 140, 3724–3735; [DOI] [PubMed] [Google Scholar]; (c) Muto K, Yamaguchi J, Musaev DG, Itami K, Decarbonylative Organoboron Cross-Coupling of Esters by Nickel Catalysis, Nat. Commun. 2015, 6(7508), 1–8; [DOI] [PMC free article] [PubMed] [Google Scholar]; (d) Desnoyer AN, Friese FW, Chiu W, Drover MW, Patrick BO, Love JA, Exploring JA Regioselective Bond Cleavage and Cross-Coupling Reactions using a Low-Valent Nickel Complex, Chem. Eur. J. 2016, 22, 4070–4077; [DOI] [PubMed] [Google Scholar]; (e) Desnoyer AN, Love JA, Recent Advances in Well-Defined, Late Transition Metal Complexes that Make and/or Break C–N, C–O and C–S Bonds, Chem. Soc. Rev. 2017, 46, 197–238; [DOI] [PubMed] [Google Scholar]; (f) Liu C, Szostak M, Decarbonylative Thioetherification by Nickel Catalysis using Air- and Moisture-Stable Nickel Precatalysts, Chem. Commun. 2018, 54, 2130–2133; [DOI] [PubMed] [Google Scholar]; (g) Zuo Z, Ahneman DT, Chu L, Terrett JA, Doyle AG, MacMillan DWC, Merging Photoredox with Nickel Catalysis: Coupling of α-Carboxyl sp3-Carbons with Aryl Halides, Science 2014, 345, 437–440; [DOI] [PMC free article] [PubMed] [Google Scholar]; (h) Behenna DC, Liu Y, Yurino T, Kim J, White DE, Virgil SC, Stoltz BM, Enantioselective Construction of Quaternary N-Heterocycles by Palladium-Catalysed Decarboxylative Allylic Alkylation of Lactams, Nat. Chem. 2012, 4, 130–133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26 (a).Dermenci A, Dong G, Decarbonylative C-C Bond Forming Reactions Mediated by Transition Metals, Sci. China Chem. 2013, 56, 685–701; [Google Scholar]; (b) Guo L, Rueping M, Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group Interconversion Strategies for the Construction of Complex Organic Molecules, Acc. Chem. Res. 2018, 5, 1185–1195; [DOI] [PubMed] [Google Scholar]; (c) Fristrup P; Kreis M; Palmelund A; Norrby PO; Madsen R The Mechanism for the Rhodium-Catalyzed Decarbonylation of Aldehydes: A Combined Experimental and Theoretical Study, J. Am. Chem. Soc. 2008, 130, 5206–5215; [DOI] [PubMed] [Google Scholar]; (d) Cavell KJ Recent Fundamental Studies on Migratory Insertion into Metal-Carbon Bonds, Coord. Chem. Rev. 1996, 155, 209–243; [Google Scholar]; (e) De La Higuera Macias M, Arndtsen BA, Functional Group Transposition: A Palladium-Catalyzed Metathesis of Ar–X σ-Bonds and Acid Chloride Synthesis, J. Am. Chem. Soc. 2018, 140, 10140–10144. [DOI] [PubMed] [Google Scholar]
  • 27.For decarbonylative borylation of carboxylic acids, see: Liu C, Ji CL, Hong X, Szostak M, Palladium-Catalyzed Decarbonylative Borylation of Carboxylic Acids: Tuning Reaction Selectivity by Computation, Angew. Chem. Int. Ed. 2018, 57, 16721–16726. [DOI] [PubMed] [Google Scholar]
  • 28.For decarbonylative reduction of carboxylic acids, see: Liu C, Qin ZX, Ji CL, Hong X, Szostak M, Highly-Chemoselective Step-down Reduction of Carboxylic Acids to Aromatic Hydrocarbons via Palladium Catalysis, Chem. Sci. 2019, 10, 5736–5742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.For decarbonylative arylation of carboxylic acids, see: Liu C, Ji CL, Qin ZX, Hong X, Szostak M , Synthesis of Biaryls via Decarbonylative Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Carboxylic Acids, iScience. 2019, 19, 749–759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.For decarbonylative phosphorylation of carboxylic acids, see: Liu C, Ji CL, Zhou T, Hong X, Szostak M, Decarbonylative Phosphorylation of Carboxylic Acids via Redox-Neutral Palladium Catalysis, Org. Lett. 2019, 21, 9256–9261. [DOI] [PubMed] [Google Scholar]
  • 31.(a) For decarbonylative Heck cross-coupling of carboxylic acid derivatives, see: Gooßen LJ, Paetzold J, Pd-Catalyzed Decarbonylative Olefination of Aryl Esters: Towards a Waste-Free Heck Reaction, Angew. Chem. Int. Ed. 2002, 41, 1237–1241; [DOI] [PubMed] [Google Scholar]; (b) Stephan MS, Teunissen AJJM, Verzijl GKM, de Vries JG, Heck Reactions without Salt Formation: Aromatic Carboxylic Anhydrides as Arylating Agents, Angew. Chem. Int. Ed. 1998, 37, 662–664; [DOI] [PubMed] [Google Scholar]; (c) For a further review, see: Zhao Q, Szostak M, Redox-Neutral Decarbonylative Cross-Couplings Coming of Age, ChemSusChem 2019, 12, 2983–2987. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

supp
NIHMS1725032-supplement-supp.pdf (19.9MB, pdf)

RESOURCES