Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2021 Aug 21.
Published in final edited form as: Org Lett. 2020 Aug 10;22(16):6434–6440. doi: 10.1021/acs.orglett.0c02250

Decarbonylative Suzuki-Miyaura Cross-Coupling of Aroyl Chlorides

Tongliang Zhou †, Pei-Pei Xie ‡, Chong-Lei Ji ‡, Xin Hong ‡, Michal Szostak †
PMCID: PMC7456303  NIHMSID: NIHMS1620261  PMID: 32806154

Abstract

Herein, we report a catalyst system for Pd-catalyzed decarbonylative Suzuki-Miyaura cross-coupling of aroyl chlorides with boronic acids to furnish biaryls. This strategy is suitable for a broad range of common aroyl chlorides and boronic acids. The synthetic utility is highlighted in the direct late-stage functionalization of pharmaceuticals and natural products capitalizing on the presence of carboxylic acid moiety. Extensive mechanistic and DFT studies provide key insight into the reaction mechanism and high decarbonylative cross-coupling selectivity.

Graphical Abstract

graphic file with name nihms-1620261-f0007.jpg

The Suzuki-Miyaura cross-coupling of aryl chlorides is one of the most powerful reactions developed (Figure 1A).1,2 On the other hand, very little progress has been made in the development of the biaryl Suzuki-Miyaura cross-coupling of aroyl chlorides.3 To date, only one catalyst system has been developed by Sanford and co-workers using Pd[P(o-tol)3]2/BrettPhos,4 however, it involves a sequential decarbonylative chlorination/aryl chloride cross-coupling rather than direct decarbonylative cross-coupling. This Suzuki reaction was successful in only two examples of electronically-activated aroyl chlorides.

Figure 1.

Figure 1.

Open in a new tab

(a) Suzuki cross-coupling of aryl chlorides. (b-c) This study: Decarbonylative Suzuki–Miyaura cross-coupling of aroyl chlorides.

Herein, we report to the best of our knowledge the first catalytic system for the direct decarbonylative Suzuki-Miyaura cross-coupling of aroyl chlorides (Figure 1B). The method employs [Pd(η3-1-t-Bu-ind)Cl]2/PPh3 or DPEPhos and NaHCO3 as a weak base to slow down transmetallation relative to decarbonylation.1d The utility of this method is highlighted in the direct functionalization of pharmaceuticals and natural products that capitalize on the presence of the carboxylic acid moiety to introduce the biaryl motif in a decarbonylative fashion (Figure 1C). Furthermore, we present detailed mechanistic and DFT studies to elucidate the mechanistic pathway and provide benchmark for the development of future synthetic methods.

In general, aroyl chlorides, R–C(O)Cl are the most fundamental and ubiquitous carboxylic acid derivatives.3 Despite some limitations, such as stability, aroyl chlorides are the most common acyl transfer reagents used on daily basis in academic and industrial laboratories worldwide.5,6 In particular, nucleophilic acyl substitution using aroyl chlorides is among the most popular synthetic methods at present,3 however, an arsenal of acyl cross-couplings of aroyl chlorides has also been developed permitting access to biaryl ketones.7

In contrast to these methods, the direct arylation of aroyl chlorides remains a major challenge. Although decarbonylative cross-couplings have been developed as a powerful reactivity manifold, few methods involving simple aroyl chlorides have been established.8 In this context, although aroyl chlorides are the most fundamental carboxylic acid derivatives,3,5,6 the biaryl Suzuki–Miyaura cross-coupling – one of the most powerful synthetic transformations within the field of chemistry1,2 – using aroyl chlorides as electrophiles remains a challenging goal.

Within our program on decarbonylative cross-coupling reactions,9 we questioned whether decarbonylative Suzuki-Miyaura cross-coupling of aroyl chlorides might be accomplished using versatile Pd catalysis.10–14 Notable features of our study include (1) the first example of a direct decarbonylative Suzuki-Miyaura cross-coupling of aroyl chlorides. Aroyl chlorides represent a fundamental functional group in organic synthesis. The reaction involves a fundamental elementary step, oxidative addition of an acyl-Cl bond (cf. acyl-OCOR bond).9f (2) a new catalytic system for decarbonylative cross-coupling of aroyl electrophiles (cf. acid anhydrides), which we believe would be useful for the development of future cross-coupling methods.

Our studies were initiated by the examination of the cross-coupling of benzoyl chloride with 4-methoxyphenyl boronic acid as the nucleophile (eq 1). The key challenge in decarbonylative cross-coupling is the reactivity of acyl- and aryl-metal intermediates in elementary organonometallic steps. After very extensive optimization (see Tables S1–S10, SI), we have identified a catalyst system consisting of [Pd(η3-t-Bu-ind)Cl]2 as the Pd source, PPh3 or DPEPhos as a phosphine ligand and NaHCO3 as a base. Under the optimized conditions, the biaryl product was formed in 93% yield with >95:5 selectivity for the biaryl vs. acyl coupling. In the model cross-coupling, the same yield was observed using preformed (η3-1-t-Bu-ind)Pd(Cl)(PPh3) and the catalyst formed in situ from [Pd(η3-1-t-Bu-ind)Cl]2 and PPh3. To our knowledge, this is the first example of a beneficial effect of allyl-supported precatalysts in decarbonylative cross-coupling, a finding which may lead to the development of more effective Pd(II) precatalysts in this catalysis platform.15–17

graphic file with name nihms-1620261-f0008.jpg (eq 1)

It is further interesting to note that a comprehensive optimization of η3-allyl throw-away ligands,15 such as η3-allyl, η3-cin, η3-ind, η3-1-t-Bu-ind in [Pd(η3-allyl)Cl]2 catalysts across various boronic acids was conducted and confirmed the beneficial effect of η3-1-t-Bu-ind in all cases examined (see SI).

With the optimized conditions in hand, the scope and limitations of this Suzuki–Miyaura cross-coupling were investigated (Scheme 1). As shown, the scope of the reaction is very broad using unbiased electrophile and accommodates a significant electronic and steric variation. As such, electron-rich (3a-3b) and electron-deficient (3c-3h) boronic acids are well-tolerated. It is noteworthy that the reaction readily accommodates electrophilic groups, such as ketones (3c), esters (3d), chlorides (3g), aldehydes (3h). In particular, the tolerance to aryl chloride (3g) highlights the orthogonal nature of decarbonylative cross-coupling vs. the conventional aryl chloride cross-coupling. Furthermore, steric-hindrance (3i-3j) and a variety of other substrates (3k-3t), including heterocycles (3r-3t) are readily accommodated by this decarbonylative cross-coupling. Importantly, the scope with respect to the aroyl chloride component is similarly broad (3u-3ak), including electrophilic substrates such as chloride (3z), ester (3ab) or cyano (3ah-3aj). Several additional points and limitations should be noted.18 At this stage, mono-ortho-substitution on acyl chlorides is tolerated, while di-ortho-substituted aroyl chlorides are not suitable substrates. The 4-nitro substituent on the boronic acid allows for the cross-coupling (4-nitro-1,1′-biphenyl, 42% yield). The ratio of 3:4 = 81:19 is consistent with the electron-withdrawing effect of the nitro group. The 4-nitro group on aroyl chloride is tolerated (4-methoxy-4′-nitro-1,1′-biphenyl, 31% yield, 3:4 >95:5). It should also be noted that aroyl chlorides are potential lachrymators (LC50 inhalation, rat, 1.45 mg/L) and have several other hazards.18d

Scheme 1.

Scheme 1.

Open in a new tab

Scope of Decarbonylative Suzuki–Miyaura Cross-Coupling of Aroyl Chloridesa

aConditions: acyl chloride (1.0 equiv), boronic acid (1.5 equiv), NaHCO3 (3 equiv), [(1-t-Bu-ind)PdCl]2 (7.5 mol%), 30 mol% PPh3, dioxane (0.10 M), 160 °C, 15 h. Isolated yields. b20 mol% DPEPhos. See SI for details.

The synthetic utility is highlighted in the direct late-stage functionalization of pharmaceuticals and natural products that feature carboxylic acid moiety that is readily converted in situ to aroyl chlorides using thionyl chloride – a classic sequence in nucleophilic acyl additions3,5,6,14 (Scheme 2). The synthesis of biaryls from probenecid (3al, antihyperuricemic), bexarotene (3am, antineoplastic), methone (3an, monoterpene) and cholesterol (3ao, steroid) illustrate the capacity of this coupling in the synthesis of biaryls with a range of potential applications.19

Scheme 2.

Scheme 2.

Open in a new tab

Late-Stage Functionalization of Pharmaceuticals and Natural Productsa

aConditions: carboxylic acid (1.0 equiv), SOCl2, DMF, toluene, 75 °C, 12 h, then boronic acid (1.5 equiv), NaHCO3 (3 equiv), [(1-t-Bu-ind)PdCl]2 (7.5 mol%), 30 mol% PPh3, dioxane (0.10 M), 160 °C, 15 h. Isolated yields. See SI for details.

To study the mechanism, we conducted stoichiometric experiments with isolated intermediates (Scheme 3 and SI).

Scheme 3.

Scheme 3.

Open in a new tab

Mechanistic Studies with Isolated Intermediates

A. To gain insight into the facility of decarbonylation, we prepared acyl-palladium complex 6 and subjected this complex to the cross-coupling (Scheme 3A). Decarbonylation of 6 occurs at 80 °C, while full conversion is achieved at 160 °C after 30 min. Furthermore, we have independently prepared aryl-Pd complex 7 (Scheme 3A).20 The reverse reaction of 7 to give 6 occurs under atmospheric pressure of CO within 2 h at rt. These findings confirm that decarbonylation of acyl-palladium 6 can occur under mild conditions at 80 °C.21 Decarbonylation of 6 is not observed at lower temperatures than 80 °C (see SI).

B. Stoichiometric experiments using benzoyl chloride in the presence of palladium precursor and phosphine ligand using [Pd] (1 equiv) (Pd(dba)2 or [Pd(η3-1-t-Bu-ind)Cl]2) and PPh3 (2 equiv) give aryl-Pd complex 7 exclusively (Scheme 3B), consistent with fast decarbonylation of acyl-palladium 6.21

C. Experiments with acyl-Pd complex 6 in the presence of boronic acid and base under different conditions show that at rt only ketone 4a resulting from acyl coupling was formed, however, at higher temperatures only biaryl 3a was observed, even after short reaction times, reaching full conversion at 160 °C after 15 min (Scheme 3C).

D. Stoichiometric experiments with 7 in the presence of boronic acid and base show full conversion of aryl-palladium 7 to biaryl 3a after 15 min at 160 °C (Scheme 3D).

E-F. Further experiments probing the effect of CO (Scheme 3E) and the potential of acyl-palladium complex 6 as a catalyst (Scheme 3F) demonstrate that acyl coupling is more facile than aryl coupling and that 6 is catalytically active, consistent with 6 as a catalytic intermediate in the cross-coupling. Scheme 4 presents a summary of stoichiometric studies. The results suggest that decarbonylation precedes transmetallation. Decarbonylation is facile and occurs at temperatures as low as 80 °C. The results indicate transmetallation as the rate-limiting step.

Scheme 4.

Scheme 4.

Open in a new tab

Summary of Mechanistic Studiesa

To gain further insight into the mechanism of this novel cross-coupling, we have performed extensive computational studies to delineate the origin of high reactivity and the energies of elementary steps. The DFT-computed free energy profile of Pd/PPh3-catalyzed decarbonylative biaryl Suzuki-Miyaura cross-coupling with benzoyl chloride is shown in Figure 2. From the substrate-coordinated complex 8, the oxidative addition of benzoyl chloride through TS9 is very facile, generating the acyl-palladium intermediate 10. 10 dissociates one of the phosphine coordinates to allow the subsequent decarbonylation via TS12, and the ligand-CO exchange leads to the bisligated aryl-palladium species 14. From 14, the base-promoted transmetallation occurs via an outer-sphere mechanism (TS16) to generate the biaryl-palladium intermediate 17. The alternative base-free, bicarbonate-facilitated, or inner-sphere transmetallation processes were found less favorable (Figure S1). 17 undergoes a facile aryl-aryl reductive elimination through TS18 to produce the produce-coordinated complex 19. Subsequent product liberation regenerates the palladium catalyst and completes the catalytic cycle. We want to emphasize that the isolated chloride anion is a simplification of its form in the catalytic system, complexation with cationic species could further stabilize the dissociated chloride anion and make the product liberation more exergonic. Based on the DFT-computed free energy profile, the rate-determining step of the catalytic cycle is the transmetallation step via TS16. This step requires an overall barrier of 29.9 kcal/mol comparing with the on-cycle resting state acyl-palladium intermediate 10.

Figure 2.

Figure 2.

Open in a new tab

DFT-computed free-energy-profile of Pd/PPh3-catalyzed decarbonylative biaryl Suzuki-Miyaura coupling of benzoyl chloride. See SI for details.

An additional point is the speciation of Pd catalyst at 160 °C. Decarbonylation of 6 to 7 occurs at 60 °C (1 h, 13%) and the entire reaction at 100 °C (3a, 21%). Therefore, we can make a reasonable assumption of catalyst speciation between 25-80 °C and apply it to our reaction conditions. Moreover, considering the boiling point of 1,4-dioxane, the system temperature should be close to 120 °C in the stoichiometric transformation. Furthermore, we have made attempts to determine the fate of the Pd in stoichiometric reactions of 7. Preliminary studies indicate the formation of Pd(PPh3)2 in the cross-coupling of 7 (0.5 h, 17%).

In summary, we have identified a new catalyst system for the decarbonylative Suzuki–Miyaura cross-coupling of aroyl chlorides. Synthetically, aroyl chlorides are the most fundamental carboxylic acid derivatives. This report demonstrates that aroyl chlorides could be successfully utilized in the powerful Suzuki-Miyaura biaryl cross-coupling manifold. The synthetic utility has been highlighted in the direct functionalization of pharmaceuticals and natural products capitalizing on the presence of carboxylic acid moiety. Mechanistic and DFT studies have provided insight into the high reaction selectivity and established facile decarbonylation, and decarbonylation preceding transmetallation. Our future studies will be focused on expanding the scope of coupling partners in this process.

Supplementary Material

SI

ACKNOWLEDGMENT

We thank the NSF (CAREER CHE-1650766, M.S.), the NIH (1R35GM133326, M.S.), Rutgers University (M.S.), NSFC (21702182 and 21873081, X.H.), Fundamental Research Funds for the Central Universities (X.H.), and Zhejiang University (X.H.) for generous financial support. Calculations were performed on the high-performance computing system at the Department of Chemistry, Zhejiang University.

Footnotes

ASSOCIATED CONTENT

Supporting Information

Experimental procedures, characterization data, computational details, coordinates and energies of DFT-computed stationary points. This material is available free of charge via the Internet at http://pubs.acs.org.

The authors declare no competing financial interest.

REFERENCES

  • (1).(a) Miyaura N; Suzuki A Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev 1995, 95, 2457–2483 [Google Scholar]; (b) Cross-Coupling and Heck-Type Reactions, 1st ed.; Molander GA; Wolfe JP; Larhed M, Eds.; Thieme: Stuttgart, 2013 [Google Scholar]; (c) New Trends in Cross-Coupling; 1st ed.; Colacot TJ, Ed.; The Royal Society of Chemistry: Cambridge, 2015 [Google Scholar]; (d) Lima CFRAC; Rodrigues ASMC; Silva VLM; Silva AMS; Santos LMNBF Role of the Base and Control of Selectivity in the Suzuki-Miyaura Cross-Coupling Reaction. ChemCatChem 2014, 6,1291–1302. [Google Scholar]
  • (2).Johansson-Seechurn CCC; Kitching MO; Colacot TJ; Snieckus V A Historical Contextual Perspective to the 2010 Nobel Prize. Angew. Chem. hit. Ed 2012, 51, 5062–5085. [DOI] [PubMed] [Google Scholar]
  • (3).(a) Brown WH; Iverson BL; Anslyn E; Foote CS Organic Chemistry, Cengage: Boston, 2018 [Google Scholar]; (b) McMurry JE Organic Chemistry, Brooks/Cole: Belmont, 2011 [Google Scholar]; (c) Smith MB; March J Advanced Organic Chemistry, John Wiley & Sons: Hoboken, 2007. [Google Scholar]
  • (4).Malapit CA; Ichiishi N; Sanford MS Pd-Catalyzed Decarbonylative Cross-Couplings of Aroyl Chlorides. Org. Tett 2017, 19, 4142–4145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (5).Roughley SD; Jordan AM The medicinal chemist’s toolbox: an analysis of reactions used in the pursuit of drug candidates. J. Med. Chem 2011. 54, 3451–3479. [DOI] [PubMed] [Google Scholar]
  • (6).Brown DG; Bostrom J Analysis of Past and Present Synthetic Methodologies in Medicinal Chemistry: Where Have all the New Reactions Gone? J. Med. Chem 2016, 59, 4443–4458. [DOI] [PubMed] [Google Scholar]
  • (7).Buchspies J; Szostak M Recent Advances in Acyl Suzuki Cross-Coupling. Catalysts 2019, 9, 53. [Google Scholar]
  • (8).For a leading study on decarbonylative biaryl synthesis using aroyl chlorides with Rh(I) catalysis via C-H activation, see:; (a) Zhao X; Yu Z Rhodium-Catalyzed Regioselective C-H Functionalization via Decarbonylation of Acid Chlorides and C-H Bond Activation under Phosphine-Free Conditions. J. Am. Chem. Soc 2008, 130, 8136–8137 [DOI] [PubMed] [Google Scholar]; For further studies see:; (b) Yasukawa T; Satoh T; Miura M; Nomura M Iridium-Catalyzed Reaction of Aroyl Chlorides with Internal Alkynes to Produce Substituted Naphthalenes and Anthracenes. J. Am. Chem. Soc 2002. 124, 12680–12681 [DOI] [PubMed] [Google Scholar]; (c) Sugihara T; Satoh T; Miura M; Nomura M Rhodium-Catalyzed Mizoroki-Heck-Type Arylation of Alkenes with Aroyl Chlorides under Phosphane- and Base-Free Conditions. Angew. Chem., Int. Ed 2003, 42, 4672–4674 [DOI] [PubMed] [Google Scholar]; (d) Iwai T; Fujihara T; Terao J; Tsuji Y Iridium-Catalyzed Addition of Acid Chlorides to Terminal Alkynes. J. Am. Chem. Soc 2009, 131, 6668–6669 [DOI] [PubMed] [Google Scholar]; (e) Pan F; Boursalian GB; Ritter T Palladium-Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature. Angew. Chem., Int. Ed 2018, 57, 16871–16876 [DOI] [PubMed] [Google Scholar]; For a recent decarbonylative cyanation of aroylchlorides see:; (f) Wang Z; Wang X; Ura Y; Nishihara Y Nickel-Catalyzed Decarbonylative Cyanation of Acyl Chlorides. Org. Tett 2019, 21, 6779–6784. [DOI] [PubMed] [Google Scholar]
  • (9).(a) 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) Zhou T; Ji C-L; Hong X; Szostak M Palladium-Catalyzed Decarbonylative Suzuki-Miyaura Cross-Coupling of Amides by Carbon-Nitrogen Bond Activation. Chem. Sci 2019,70, 9865–9871 [DOI] [PMC free article] [PubMed] [Google Scholar]; (d) 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]; (e) Ji C-L; 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]; (f) Liu C; Ji C-L; Qin Z-X; 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]; (g) Liu C; Ji C-L; 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]; (h) Liu C; Qin Z-X; Ji C-L; 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]; (i) 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]; (j) 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]
  • (10).(a) Zhao Q; Szostak M Redox-Neutral Decarbonylative Cross-Couplings Coming of Age. ChemSusChem 2019, 12,2983–2987 [DOI] [PubMed] [Google Scholar]; (b) Liu C; Szostak M Decarbonylative Cross-Coupling of Amides. Org. Biomol. Chem 2018. 16, 7998–8010 [DOI] [PubMed] [Google Scholar]; (c) Dzik WI; Lange PP; Gooßen LJ Carboxylates as Sources of Carbon Nucleophiles and Electrophiles: Comparison of Decarboxylative and Decarbonylative Pathways. Chem. Sci 2012, 3, 2671–2678 [Google Scholar]; (d) GooBen LJ; Rodriguez N; GooBen K Carboxylic Acids as Substrates in Homogeneous Catalysis. Angew. Chem. Int. Ed 2008, 47, 3100–3120. [DOI] [PubMed] [Google Scholar]
  • (11).For representative examples of decarbonylative cross-couplings, see:; (a) Ogiwara Y; Sakurai Y; Hattori H; Sakai N Palladium-Catalyzed Reductive Conversion of Acyl Fluorides via Ligand-Controlled Decarbonylation. Org. Lett 2018, 20, 4204–4208 [DOI] [PubMed] [Google Scholar]; (b) Ogiwara Y; Sakai N Acyl Fluorides in Late-Transition-Metal Catalysis. Angew. Chem., Int. Ed 2020, 59, 574–594 [DOI] [PubMed] [Google Scholar]; (c) 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]; (d) Malapit CA; Bour JR; Brigham CE; Sanford MS Base-Free Nickel-Catalysed Decarbonylative Suzuki-Miyaura Coupling of Acid Fluorides. Nature 2018, 563, 100–104 [DOI] [PMC free article] [PubMed] [Google Scholar]; (e) Muto K; Yamaguchi J; Musaev DG; Itami K Decarbonylative Organoboron Cross-Coupling of Esters by Nickel Catalysis. Nat. Commun 2015, 6, 7508. [DOI] [PMC free article] [PubMed] [Google Scholar]; (f) Guo L; Srimontree W; Zhu C; Maity B; Liu X; Cavallo L; Rueping M Nickel-Catalyzed Suzuki-Miyaura Cross-Couplings of Aldehydes. Nat. Commun 2019, 10, 1957. [DOI] [PMC free article] [PubMed] [Google Scholar]; (g) Zhao T-T; Xu W-H; Zheng Z-J; Xu P-F; Wei FI. Directed Decarbonylation of Unstrained Aryl Ketones via Nickel-Catalyzed C-C Bond Cleavage. J. Am. Chem. Soc 2018, 140, 586–589 [DOI] [PubMed] [Google Scholar]; (h) Lei ZQ; Pan F; Li H; Li Y; Zhang XS; Chen K; Wang X; Li YX; Sun J; Shi ZJ Group Exchange between Ketones and Carboxylic Acids through Directing Group Assisted Rh-Catalyzed Reorganization of Carbon Skeletons. J. Am. Chem. Soc 2015,137, 5012–5020. [DOI] [PubMed] [Google Scholar]
  • (12).For representative decarboxylative cross-couplings via photoredox catalysis, see:; (a) 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]; (b) Twilton J; Le CC; Zhang P; Shaw MFI; Evans RW; MacMillan DWC The merger of transition metal and photocatalysis. Nat. Rev. Chem 2017, 1, 52. [Google Scholar]
  • (13).For representative decarboxylative cross-couplings via redox-active esters, see:; (a) Qin T; Cornelia J; Li C; Malins LR; Edwards JT; Kawamura S; Maxwell BD; Eastgate MD; Baran PS A general alkyl-alkyl cross-coupling enabled by redox-active esters and alkylzinc reagents. Science 2016, 352, 801–805 [DOI] [PMC free article] [PubMed] [Google Scholar]; (b) Edwards JT; Merchant RR; McClymont KS; Knouse KW; Qin T; Malins LR; Vokits B; Shaw SA; Bao DH; We FL; Zhou T; Eastgate MD; Baran PS Decarboxylative alkenylation. Nature 2017, 545, 213–218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (14).For classic examples of using aroyl chlorides in synthesis, see:; (a) Corey EJ; Cheng XM The Logic of Chemical Synthesis, John Wiley & Sons: New York, 1995 [Google Scholar]; (b) Nicolaou KC; Chen JS Classics in Total Synthesis III: Further Targets, Strategies, Methods, Wiley: Weinheim, 2011. [Google Scholar]
  • (15).(a) Marion N; Navarro O; Mei J; Stevens ED; Scott NM ; Nolan SP Modified (NHC)Pd(allyl)Cl (NHC = N-heterocyclic carbene) complexes for room-temperature Suzuki-Miyaura and Buchwald-Hartwig reactions. J. Am. Chem. Soc 2006, 128, 4101–4111 [DOI] [PubMed] [Google Scholar]; (b) Marion N; Nolan SP Well-defined N-heterocyclic carbenes-palladium(II) precatalysts for cross-coupling reactions. Ace. Chem. Res 2008, 41, 1440–1449 [DOI] [PubMed] [Google Scholar]; (c) Hruszkewycz DP; Balcells D; Guard LM; Hazari N; Tilset M Insight into the Efficiency of Cinnamyl-Supported Precatalysts for the Suzuki-Miyaura Reaction: Observation of Pd(I) Dimers with Bridging Allyl Ligands During Catalysis. J. Am. Chem. Soc 136, 20, 7300–7316 [DOI] [PubMed] [Google Scholar]; (d) Melvin PR; Nova A; Balcells D; Dai W; Hazari N; Hruszkewycz DP; Shah MP; Tudge MT Design of a Versatile and Improved Precatalyst Scaffold for Palladium-Catalyzed Cross-Coupling: (η3-1-t-Bu-indenyl)2(μ-Cl)2Pd2. ACS Catal 2015, 5, 5596–5606. [Google Scholar]
  • (16).(a) Li H; Johansson-Seechurn CCC; Colacot TJ Development of Preformed Pd Catalysts for Cross-Coupling Reactions, Beyond the 2010 Nobel Prize. ACS Catal 2012, 2, 1147–1164 [Google Scholar]; (b) Hazari N; Melvin PR; Beromi MM Well-defined nickel and palladium precatalysts for cross-coupling. Nat. Rev. Chem 2017, 1, 25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • (17).For decarbonylative dehydration, see:; (a) Chatterjee A; Eliasson SMH; Törnroos KW; Jensen VR Palladium Precatalysts for Decarbonylative Dehydration of Fatty Acids to Linear Alpha Olefins. ACS Catal 2016, 6, 7784–7789 [Google Scholar]; (b) Zhang X; Jordan F; Szostak M Transition-Metal-Catalyzed Decarbonylation of Carboxylic Acids to Olefins: Exploiting Acyl C-O Activation for the Production of High Value Products. Org. Chem. Front 2018, 5, 2515–2521. [Google Scholar]
  • (18).Several additional points should be noted: (a) at present stage of reaction development, the method tolerates free OH, but the yields are low; (b) NaHCO3 is fully soluble in 1,4-dioxane under our conditions; (c) limitations include sterically-hindered chlorides, 2-heteroaryl chlorides and substrates containing active hydrogen atoms. The latter limitation is typical to the use of aroyl chlorides in synthesis.3,4,5,14; Hazardous Substances Data Bank (HSDB). https://pubchem.ncbi.nlm.nih.gov/source/hsdb/383 (accessed, July 30, 2020).
  • (19).(a) Yet L Privileged Structures in Drug Discovery: Medicinal Chemistry and Synthesis, Wiley: Hoboken, 2018 [Google Scholar]; (b) Blakemore DC; Castro L; Churcher I; Rees DC; Thomas AW; Wilson DM; Wood A Organic Synthesis Provides Opportunities to Transform Drug Discovery. Nat. Chem 2018, 10, 383–394. [DOI] [PubMed] [Google Scholar]
  • (20).(a) Andersen TL; Friis SD; Audrain H; Nordeman P; Antoni G; Skrydstrup T Efficient 11C-Carbonylation of Isolated Aryl Palladium Complexes for PET: Application to Challenging Radiopharmaceutical Synthesis. J. Am. Chem. Soc 2015, 137, 1548–1555 [DOI] [PubMed] [Google Scholar]; (b) Herrmann WA; Brossmer C; Priermeier TH; Ôfele K Komplexchemie und Mechanismen Metallkatalysierter CC Kupplungsreaktionen: II. Oxidative Addition von Chloraromaten an PdO-Komplexe: Synthese, Struktur und Stabilität von Arylpalladium(II)-chloriden der Phosphanreihe. J. Organomet. Chem 1994, 481, 97–108. [Google Scholar]
  • (21).(a) Cavell KJ Recent fundamental studies on migratory insertion into metal-carbon bonds. Coord. Chem. Rev 1996, 155, 209–243 [Google Scholar]; (b) Brennführer A; Neumann H; Beller M Palladium-catalyzed carbonylation reactions of aryl halides and related compounds. Angew. Chem. Int. Ed 2009, 48, 4114–4133 [DOI] [PubMed] [Google Scholar]; (c) Friis SD; Lindhardt AT; Skrydstrup T The Development and Application of Two-Chamber Reactors and Carbon Monoxide Precursors for Safe Carbonylation Reactions. Acc. Chem. Res 2016, 49, 594–605. [DOI] [PubMed] [Google Scholar]

Associated Data

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

Supplementary Materials

SI
NIHMS1620261-supplement-SI.pdf (8.3MB, pdf)

RESOURCES