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. 2025 Feb 25;27(9):2049–2052. doi: 10.1021/acs.orglett.4c04756

Collective Total Synthesis of Four Ganoderma Meroterpenoids Based on an Intramolecular Aldol Strategy

Yasuhiro Meguro 1,*, Mari Oyake 1, Masaru Enomoto 1, Shigefumi Kuwahara 1,*
PMCID: PMC11894643  PMID: 39994830

Abstract

graphic file with name ol4c04756_0006.jpg

The total synthesis of four Ganoderma meroterpenoids (lingzhiol, sinensilactam A, lingzhilactone B, and applanatumol I) has been accomplished from a known olefinic lactone in much shorter steps (4–8 steps) and markedly improved overall yields (15–27%) compared to previous syntheses. The key steps are highly regio- and diastereoselective intramolecular aldol reactions to prepare bicyclic lactone intermediates and a decarboxylative radical cyclization to install the unique tetracyclic ring system of lingzhiol.

Polypore fungi of the genus Ganoderma have long been utilized as traditional natural medicines in East Asia for the treatment of various diseases such as cancer and kidney disorders.1 Among a wide range of metabolites produced by this group of fungi, the discovery of ganomycins A and B, antimicrobial farnesylhydroquinone derivatives, as the first meroterpenoids from G. pfeifferi in 2000 and, especially, the isolation of lingzhiol (1) with useful pharmacological profiles in 2013 have attracted the interest of natural product chemists in Ganoderma meroterpenoids as an important reservoir for drug discovery.1,2 Lingzhiol (1),2b sinensilactam A (2),3 lingzhilactone B (3),1d and applanatumol I (4)4 are meroterpenoids found in G. lucidum, G. sinensis, G. lingzhi, and G. applanatum, respectively (Figure 1). Quite interestingly, these natural products were all isolated as their racemates. Compounds 1 and 2 inhibit the phosphorylation of Smad3, a proteinous factor playing an important role in the TGF-β/Smad3 signaling pathway, and accordingly have the potential to lead to the development of new renoprotective agents.1 It is worthy of note that both enantiomers of 1 and 2 separated by chiral HPLC inhibited the phosphorylation of Smad3, and their (−)-isomers were more active than the corresponding (+)-isomers.2b,3 Lingzhilactone B (3) is also a Smad3 phosphorylation inhibitor,1d while no bioactivity is reported for 4.4

Figure 1.

Figure 1

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Structures of the four Ganoderma meroterpenoids.

From a structural viewpoint, they share a shikimate-derived hydroquinone unit and monoterpene-originated bicyclic lactone motif A in common, linked together by a keto-methylene bridge. The unique oxapropellane-type 6/6/5/5 ring system of 1 and the unusual 1,3-oxazinane-incorporating tetracyclic fused ring scaffold in 2 captured attention from synthetic chemists, and seven research groups have addressed the total synthesis of these meroterpenoids, focusing mainly on lingzhiol (1). The first total synthesis of 1 was accomplished enantioselectively in 17 steps (5.8% overall yield) by Yang et al.5,6 The other syntheses of 1, either in a racemic or enantioselective fashion, were achieved in 8–21 steps (0.23–10% overall yields).7 On the other hand, sinensilactam A (2) was synthesized by two research groups in 18 steps (0.4% overall yield) and in 14 steps (1.1% overall yield),7h,8 while the syntheses of lingzhilactone B (3) and applanatumol I (4) were performed in 13–17 steps (0.53–9.2% overall yields)7h,7i,8,9 and in 14 steps (1.6% overall yield),7i respectively. Although quite intriguing in terms of strategy and methodology, the syntheses reported so far seemed to leave room for improvement in the number of steps and overall yield. In this Letter, we describe a collective total synthesis of 1–4 based on a simple intramolecular aldol strategy.

The retrosynthetic analysis of 1–4 is delineated in Scheme 1. To obtain lingzhiol (1), we envisaged the C3–C7′ bond-forming cyclization of radical species B generated by the decarboxylation of 4′. The acid 4′ should be accessible by oxidation of aldehyde 3′, and, assuming the condensation of 3′ and 5-methoxypyrrolidin-2-one (5), 3′ could also serve as a precursor of sinensilactam A (2). Since 3′ is a β-hydroxy aldehyde, it would be forged by intramolecular aldol reaction of dial 6, which in turn should be obtained by oxidative cleavage of diene 7a or keto olefin 7b. Finally, 7a and 7b were traced back to commercially available olefinic lactone 8 with its α-alkylation in mind. It should be noted that the starting lactone 8 used in this synthesis is racemic, although it can also be prepared in its optically active forms [see the Supporting Information (SI)].10,11

Scheme 1. Retrosynthetic Analysis of 1–4.

Scheme 1

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The synthesis of sinensilactam A (2) and lingzhilactone B (3) via diene 7a commenced with the propargylation of 8 to give 9 in 97% yield (Scheme 2). Palladium-catalyzed hydroarylation of 9 with commercially available boronic acid 10 proceeded smoothly to afford 7a in 83% yield.12 Oxidative cleavage of 7a was first attempted by using Lemieux–Johnson conditions (OsO4/NaIO4, OsO4/NMO/NaIO4 or KIO4, OsO4/NaIO4/2,6-lutidine, etc.),13 which however gave a complex mixture containing mainly the desired keto dial 6 and olefinic dial 11 due to sluggish reactivity of the methylenic double bond at C1′. On the other hand, ozonolysis of 7a (ca. 10 mg, 10 mM concentration in CH2Cl2) under strictly time-controlled conditions (30 s) gave 6, which was exposed to BBr3 to perform its Lewis acid-promoted intramolecular aldol reaction and deprotection of the two methyl groups at the aromatic part in a single operation, furnishing 3 in 48% overall yield from 7a, with no other isomers detected. The excellent selectivity of this transformation would be explained by assuming chairlike transition state TS1 bearing a Z-configured boron enolate structure. Other transition states leading to isomers of 3 would be less stable or less reactive than TS1 (see SI for details).14,15 Finally, condensation of 3 with 5(16) in the presence of CSA successfully furnished 2 in 85% yield. Thus, the total synthesis of 3 and 2 was accomplished in 4 steps (39% overall yield) and in 5 steps (33% overall yield), respectively, from 8. This synthesis, however, had a serious drawback in terms of reproducibility of the ozonolysis step from 7a to 6. As mentioned above, time control of the reaction was strict probably due to undesired oxidation of the aromatic part of 7a, and either prolonged or shortened reaction times resulted in a decrease in chemical yield, sometimes affording 3 in less than 10% yield. Faced with this problem, we examined the Lemieux–Johnson oxidation of keto olefin 7b instead of diene 7a.

Scheme 2. Synthesis of Lingzhilactone B (3) and Sinensilactam A (2) via Diene 7a.

Scheme 2

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The preparation of 7b and its conversion into 3 and 2 is shown in Scheme 3. Dropwise addition of LiHMDS to a mixture of 8 and nitro acetate 12 effected the in situ generation of nitroalkene C and the formation of the lithium enolate of 8, successfully providing their conjugate addition product 13 as a diastereomeric mixture at C1′ (see SI for the preparation of 12).17 The Nef reaction of 13 using Hayashi’s protocol furnished 7b,18 the alternative substrate for the Lemieux–Johnson oxidation, in 52% overall yield from 8. Treatment of 7b with OsO4/NaIO4/2,6-lutidine gave 6,13c which was then exposed to BBr3 to deliver lingzhilactone B (3) in 52% yield over two steps in a highly reproducible manner. The aldol 3 was converted into 2 according to the protocol established in Scheme 2.

Scheme 3. Synthesis of Lingzhilactone B (3) and Sinensilactam A (2) via Keto Olefin 7b.

Scheme 3

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The synthesis of applanatumol I (4) by oxidation of lingzhilactone B (3) and that of lingzhiol (1) via decarboxylative radical cyclization are depicted in Scheme 4.19 The oxidation of 3 was conducted under Pinnick conditions, giving 4 in 93% yield.7i To generate radical species B′ from 4, we chose a simple and direct protocol reported by Lee et al.20 Subjection of 4 to the Lee conditions [(NH4)2S2O8, 2,4,6-collidine, DMSO], however, resulted in the recovery of 4. We next examined the cyclization of 15 with two phenolic hydroxyls protected as methyl ethers. The acid substrate 15 was obtained by the Pinnick oxidation of protected aldol 14, which in turn was prepared as a single diastereomer in 68% overall yield from 7b via the Lemieux–Johnson oxidation and subsequent intramolecular aldol reaction of the resulting dial 6 using tritylium tetrafluoroborate (TrBF4).21 Disappointingly however, attempted cyclization of 15 to di-O-methyl lingzhiol 1′ under Lee’s conditions also ended in the recovery of 15. Eventually, we prepared 17 by triethylsilylation of 14 followed by oxidation of resulting product 16. Fortunately, exposure of 17 to Lee’s conditions at 80 °C successfully brought about the cyclization to give tetracycle 1″, probably via D, in an acceptable yield of 63% (see SI for a plausible mechanism).20,22 Finally, the global deprotection of 1″ delivered lingzhiol (1) in 80% yield.

Scheme 4. Synthesis of Applanatumol I (4) and Lingzhiol (1).

Scheme 4

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In conclusion, the total synthesis of lingzhiol (1), sinensilactam A (2), lingzhilactone B (3), and applanatumol I (4) has been achieved from lactone 8 in much shorter steps and in markedly better overall yields (8 steps/15%, 5 steps/23%, 4 steps/27%, and 5 steps/25%, respectively) compared to previous syntheses. The conciseness and efficiency of the synthesis were realized by successful regio- and diastereoselective intramolecular aldol reactions to construct bicyclic lactone intermediates 3 and 3′ and exploitation of persulfate-promoted radical cyclization to deliver tetracycle 1″ directly from the corresponding acid precursor 17.

Acknowledgments

This work was financially supported by JSPS KAKENHI (20H02920 and 23K13892), and Research Support Project for Life Science and Drug Discovery (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED (JP23ama121040). Thanks are due to Ms. Yuka Taguchi (Tohoku University) for help with NMR and MS measurements.

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.4c04756.

  • Experimental procedures, characterization data, and NMR spectra (PDF)

The authors declare no competing financial interest.

Supplementary Material

ol4c04756_si_001.pdf (3.2MB, pdf)

References

  1. a Peng X.; Qiu M. Meroterpenoids from Ganoderma Species: A Review of Last Five Years. Nat. Prod. Bioprospect. 2018, 8, 137–149. 10.1007/s13659-018-0164-z. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Peng X.-R.; Unsicker S. B.; Gershenzon J.; Qiu M.-H. Structural Diversity, Hypothetical Biosynthesis, Chemical Synthesis, and Biological Activity of Ganoderma Meroterpenoids. Nat. Prod. Rep. 2023, 40, 1354–1392. 10.1039/D3NP00006K. [DOI] [PubMed] [Google Scholar]; c Zhang J.-J.; Qin F.-Y.; Cheng Y.-X. Insights into Ganoderma Fungi Meroterpenoids Opening a New Era of Racemic Natural Products in Mushrooms. Med. Res. Rev. 2024, 44, 1221–1266. 10.1002/med.22006. [DOI] [PubMed] [Google Scholar]; d Yan Y.-M.; Wang X.-L.; Zhou L.-L.; Zhou F.-J.; Li R.; Tian Y.; Zuo Z.-L.; Fang P.; Chung A. C. K.; Hou F.-F.; Cheng Y.-X. Lingzhilactones from Ganoderma lingzhi Ameliorate Adriamycin-Induced Nephropathy in Mice. J. Ethnopharmacol. 2015, 176, 385–393. 10.1016/j.jep.2015.11.024. [DOI] [PubMed] [Google Scholar]
  2. a Mothana R. A. A.; Jansen R.; Jülich W.-D.; Lindequist U. Ganomycins A and B, New Antimicrobial Farnesyl Hydroquinones from the Basidiomycete Ganoderma pfeifferi. J. Nat. Prod. 2000, 63, 416–418. 10.1021/np990381y. [DOI] [PubMed] [Google Scholar]; b Yan Y.-M.; Ai J.; Zhou L.-L.; Chung A. C. K.; Li R.; Nie J.; Fang P.; Wang X.-L.; Luo J.; Hu Q.; Hou F.-F.; Cheng Y.-X. Lingzhiols, Unprecedented Rotary Door-Shaped Meroterpenoids as Potent and Selective Inhibitors of p-Smad3 from Ganoderma lucidum. Org. Lett. 2013, 15, 5488–5491. 10.1021/ol4026364. [DOI] [PubMed] [Google Scholar]
  3. Luo Q.; Tian L.; Di L.; Yan Y.-M.; Wei X.-Y.; Wang X.-F.; Cheng Y.-X. (±)-Sinensilactam A, a Pair of Rare Hybrid Metabolites with Smad3 Phosphorylation Inhibition from Ganoderma sinensis. Org. Lett. 2015, 17, 1565–1568. 10.1021/acs.orglett.5b00448. [DOI] [PubMed] [Google Scholar]
  4. Luo Q.; Yang X.-H.; Yang Z.-L.; Tu Z.-C.; Cheng Y.-X. Miscellaneous Meroterpenoids from Ganoderma applanatum. Tetrahedron 2016, 72, 4564–4574. 10.1016/j.tet.2016.06.019. [DOI] [Google Scholar]
  5. Long R.; Huang J.; Shao W.; Liu S.; Lan Y.; Gong J.; Yang Z. Asymmetric Total Synthesis of (−)-Lingzhiol via a Rh-Catalysed [3 + 2] Cycloaddition. Nat. Commun. 2014, 5, 5707. 10.1038/ncomms6707. [DOI] [PubMed] [Google Scholar]
  6. The numbering of carbons follows that in ref (2b).
  7. a Chen D.; Liu H.-M.; Li M.-M.; Yan Y.-M.; Xu W.-D.; Li X.-N.; Cheng Y.-X.; Qin H.-B. Concise Synthesis of (±)-Lingzhiol via Epoxy-Arene Cyclization. Chem. Commun. 2015, 51, 14594–14596. 10.1039/C5CC05680B. [DOI] [PubMed] [Google Scholar]; b Gautam K. S.; Birman V. B. Biogenetically Inspired Synthesis of Lingzhiol. Org. Lett. 2016, 18, 1499–1501. 10.1021/acs.orglett.5b03212. [DOI] [PubMed] [Google Scholar]; c Li X.; Liu X.; Jiao X.; Yang H.; Yao Y.; Xie P. An Approach to (±)-Lingzhiol. Org. Lett. 2016, 18, 1944–1946. 10.1021/acs.orglett.6b00542. [DOI] [PubMed] [Google Scholar]; d Chen D.; Xu W.-D.; Liu H.-M.; Li M.-M.; Yan Y.-M.; Li X.-N.; Li Y.; Cheng Y.-X.; Qin H.-B. Enantioselective Total Synthesis of (+)-Lingzhiol via Tandem Semipinacol Rearrangement/Friedel–Crafts Type Cyclization. Chem.Commun. 2016, 52, 8561–8564. 10.1039/C6CC03764J. [DOI] [PubMed] [Google Scholar]; e Rengarasu R.; Maier M. E. Total Synthesis of Lingzhiol and Its Analogues Through the Wittig Reaction of an Oxocyclopentane Carboxylate. Asian J. Org. Chem. 2017, 6, 108–117. 10.1002/ajoc.201600455. [DOI] [Google Scholar]; f Mehl L.-M.; Maier M. E. A Radical-Based Synthesis of Lingzhiol. J. Org. Chem. 2017, 82, 9844–9850. 10.1021/acs.joc.7b01416. [DOI] [PubMed] [Google Scholar]; g Riehl P. S.; Richardson A. D.; Sakamoto T.; Schindler C. S. Eight-Step Enantiodivergent Synthesis of (+)- and (−)-Lingzhiol. Org. Lett. 2020, 22, 290–294. 10.1021/acs.orglett.9b04322. [DOI] [PubMed] [Google Scholar]; h Zhang D.-W.; Fan H.-L.; Zhang W.; Li C.-J.; Luo S.; Qin H.-B. Collective Enantioselective Total Synthesis of (+)-Sinensilactam A, (+)-Lingzhilactone B and (−)-Lingzhiol: Divergent Reactivity of Styrene. Chem. Commun. 2020, 56, 10066–10069. 10.1039/D0CC04064A. [DOI] [PubMed] [Google Scholar]; i Rode A.; Müller N.; Kováč O.; Wurst K.; Magauer T. A General Entry to Ganoderma Meroterpenoids: Synthesis of Applanatumol E, H, and I, Lingzhilactone B, Meroapplanin B, and Lingzhiol. Org. Lett. 2024, 26, 9017–9021. 10.1021/acs.orglett.4c03192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Shao W.; Huang J.; Guo K.; Gong J.; Yang Z. Total Synthesis of Sinensilactam A. Org. Lett. 2018, 20, 1857–1860. 10.1021/acs.orglett.8b00380. [DOI] [PubMed] [Google Scholar]
  9. Chen D.; Li X.-M.; Liu H.-M.; Li M.-M.; Cheng Y.-X.; Qin H.-B. Total Synthesis of (±)-Lingzhilactone B via Semipinacol Rearrangement. Tetrahedron Lett. 2016, 57, 2877–2879. 10.1016/j.tetlet.2016.05.063. [DOI] [Google Scholar]
  10. (a) For (±)-8, see:; a Corey E. J.; Petrzilka M. Formation of Macrocyclic Structures by Use of the Diels–Alder Reaction. Tetrahedron Lett. 1975, 16, 2537–2540. 10.1016/S0040-4039(00)75172-0. [DOI] [Google Scholar]; b Cayzer T. N.; Wong L. S.-M.; Turner P.; Paddon-Row M. N.; Sherburn M. S. Optimising Stereoselectivity in Intramolecular Diels–Alder Reactions of Pentadienyl Acrylates: Synthetic and Computational Investigations into the “Steric Directing Group” Approach. Chem.—Eur. J. 2002, 8, 739–750. . [DOI] [PubMed] [Google Scholar]
  11. For optically active forms of 8, see:; Ishihara J.; Nakadachi S.; Watanabe Y.; Hatakeyama S. Lewis Acid Template-Catalyzed Asymmetric Diels–Alder Reaction. J. Org. Chem. 2015, 80, 2037–2041. 10.1021/acs.joc.5b00055. [DOI] [PubMed] [Google Scholar]
  12. Oh C. H.; Jung H. H.; Kim K. S.; Kim N. The Palladium-Catalyzed Addition of Organoboronic Acids to Alkynes. Angew. Chem., Int. Ed. 2003, 42, 805–808. 10.1002/anie.200390214. [DOI] [PubMed] [Google Scholar]
  13. a Pappo R.; Allen D. S. Jr.; Lemieux R.; Johnson W. Osmium Tetroxide-Catalyzed Periodate Oxidation of Olefinic Bonds. J. Org. Chem. 1956, 21, 478–479. 10.1021/jo01110a606. [DOI] [Google Scholar]; b VanRheenen V.; Kelly R. C.; Cha D. Y. An improved catalytic OsO4 oxidation of olefins to cis-1,2-glycols using tertiary amine oxides as the oxidant. Tetrahedron Lett. 1976, 17, 1973–1976. 10.1016/S0040-4039(00)78093-2. [DOI] [Google Scholar]; c Yu W.; Mei Y.; Kang Y.; Hua Z.; Jin Z. Improved Procedure for the Oxidative Cleavage of Olefins by OsO4–NaIO4. Org. Lett. 2004, 6, 3217–3219. 10.1021/ol0400342. [DOI] [PubMed] [Google Scholar]
  14. a Mukaiyama T.; Matsuo J.. Boron and Silicon Enolates in Crossed Aldol Reaction. In Modern Aldol Reactions; Mahrwald R., Ed.; Wiley-VCH, Weinheim, 2004; Vol. 1, pp 127–160. [Google Scholar]; b Mukaiyama T.; Inoue T. New Cross-Aldol Reaction via Vinyloxyboranes. Chem. Lett. 1976, 5, 559–562. 10.1246/cl.1976.559. [DOI] [Google Scholar]; c Inoue T.; Uchimaru T.; Mukaiyama T. New Directed Cross-Aldol Reaction Using 9-Trifluoromethylsulfonyl-9-Borabicyclo[3.3.1]nonane. Chem. Lett. 1977, 6, 153–154. 10.1246/cl.1977.153. [DOI] [Google Scholar]
  15. For general discussion on the regioselectivity of intramolecular aldol reactions, see: List B.Amine-Catalyzed Aldol Reactions. In Modern Aldol Reactions; Mahrwald R., Ed.; Wiley-VCH, Weinheim, 2004; Vol. 1, pp 161–200. [Google Scholar]
  16. a Ilkei V.; Bana P.; Tóth F.; Palló A.; Holczbauer T.; Czugler M.; Sánta Z.; Dékány M.; Szigetvári A.; Hazai L.; Szántay C. Jr.; Szántay C.; Kalaus G. A Simple Synthesis of Bannucine and 5′-Epibannucine from (−)-Vindoline. Tetrahedron 2015, 71, 9579–9586. 10.1016/j.tet.2015.10.020. [DOI] [Google Scholar]; b Kerns J. K.; Busch-Petersen J.; Fu W.; Boehm J. C.; Nie H.; Muratore M.; Bullion A.; Lin G.; Li H.; Davis R.; Lin X.; Lakdawala A. S.; Cousins R.; Field R.; Payne J.; Miller D. D.; Bamborough P.; Christopher J. A.; Baldwin I.; Osborn R. R.; Yonchuk J.; Webb E.; Rumsey W. L. 3,5-Disubstituted-indole-7-carboxamides as IKKβ Inhibitors: Optimization of Oral Activity via the C3 Substituent. ACS Med. Chem. Lett. 2018, 9, 1164–1169. 10.1021/acsmedchemlett.8b00291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. a Forzato C.; Nitti P.; Pitacco G.; Valentin E.; Morganti S.; Rizzato E.; Spinelli D.; Dell’Erba C.; Petrillo G.; Tavani C. Nitroalkylation and Nitroalkenylation Reactions of γ-Lactone Enolates. A Facile Ring Switch from Polysubstituted γ-Lactones to Polysubstituted γ-Lactams. Tetrahedron 2004, 60, 11011–11027. 10.1016/j.tet.2004.07.084. [DOI] [Google Scholar]; b Moorthy N. V. G.; Dyapa R.; Pansare S. V. Formal Synthesis of (+)-Lasubine II and (−)-Subcosine II via Organocatalytic Michael Addition of a Ketone to an α-Nitrostyrene. Org. Lett. 2015, 17, 5312–5315. 10.1021/acs.orglett.5b02677. [DOI] [PubMed] [Google Scholar]
  18. Umemiya S.; Nishino K.; Sato I.; Hayashi Y. Nef Reaction with Molecular Oxygen in the Absence of Metal Additives, and Mechanistic Insights. Chem.—Eur. J. 2014, 20, 15753–15759. 10.1002/chem.201403475. [DOI] [PubMed] [Google Scholar]
  19. For examples of radical-mediated intramolecular alkylation of benzene rings, see:; a Davies D. I.; Waring C. Cyclisation Reactions Involving the Oxidation of Carboxylic Acids with Lead Tetra-acetate. Part II. The Conversion of 5-Arylvaleric Acids into 1,2,3,4-Tetrahydronaphthalenes. J. Chem. Soc. C 1968, 1865–1869. 10.1039/j39680001865. [DOI] [Google Scholar]; b Sherwood T. C.; Xiao H.-Y.; Bhaskar R. G.; Simmons E. M.; Zaretsky S.; Rauch M. P.; Knowles R. R.; Dhar T. G. M. Decarboxylative Intramolecular Arene Alkylation Using N-(Acyloxy)phthalimides, an Organic Photocatalyst, and Visible Light. J. Org. Chem. 2019, 84, 8360–8379. and references cited therein 10.1021/acs.joc.9b00432. [DOI] [PubMed] [Google Scholar]
  20. a Sutherland D. R.; Veguillas M.; Oates C. L.; Lee A.-L. Metal-, Photocatalyst-, and Light-Free, Late-Stage C–H Alkylation of Heteroarenes and 1,4-Quinones Using Carboxylic Acids. Org. Lett. 2018, 20, 6863–6867. 10.1021/acs.orglett.8b02988. [DOI] [PubMed] [Google Scholar]; b McLean E. B.; Mooney D. T.; Burns D. J.; Lee A.-L. Direct Hydrodecarboxylation of Aliphatic Carboxylic Acids: Metal- and Light-Free. Org. Lett. 2022, 24, 686–691. 10.1021/acs.orglett.1c04079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. a Kobayashi S.; Murakami M.; Mukaiyama T. Trityl Salts as Efficient Catalysts in the Aldol Reaction. Chem. Lett. 1985, 14, 1535–1538. 10.1246/cl.1985.1535. [DOI] [Google Scholar]; b Zhao S.; Zhang J.; Zhai Y.; Zou X.; Wang S.; Bian Z.; Cui F.; Zhu G. Highly Efficient Lewis Acid Catalytic Activity of the Tritylium Ion at the Node of a Tensile Organic Framework. Chem. Sci. 2021, 12, 9786–9793. 10.1039/D1SC02594E. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. a Lu S.; Gong Y.; Zhou D. Transition Metal-Free Oxidative Radical Decarboxylation/Cyclization for the Construction of 6-Alkyl/Aryl Phenanthridines. J. Org. Chem. 2015, 80, 9336–9341. 10.1021/acs.joc.5b01518. [DOI] [PubMed] [Google Scholar]; b Jin Y.; Yang H.; Fu H. Thiophenol-Catalyzed Visible-Light Photoredox Decarboxylative Couplings of N-(Acetoxy)phthalimides. Org. Lett. 2016, 18, 6400–6403. 10.1021/acs.orglett.6b03300. [DOI] [PubMed] [Google Scholar]; c Mooney D. T.; Donkin B. D. T.; Demirel N.; Moore P. R.; Lee A.-L. Direct C–H Functionalization of Phenanthrolines: Metal- and Light-Free Dicarbamoylations. J. Org. Chem. 2021, 86, 17282–17293. 10.1021/acs.joc.1c02425. [DOI] [PubMed] [Google Scholar]

Associated Data

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

Supplementary Materials

ol4c04756_si_001.pdf (3.2MB, pdf)

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

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